The DOI matches its Crossref record; 39 of the 40 references it cites were found in a registry or an index; 3 of the 48 sources its claims cite were checked for support.
Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity: The STEP 4 Randomized Clinical Trial
Open accessAbstract
Importance: The effect of continuing vs withdrawing treatment with semaglutide, a glucagon-like peptide 1 receptor agonist, on weight loss maintenance in people with overweight or obesity is unknown. Objective: To compare continued once-weekly treatment with subcutaneous semaglutide, 2.4 mg, with switch to placebo for weight maintenance (both with lifestyle intervention) in adults with overweight or obesity after a 20-week run-in with subcutaneous semaglutide titrated to 2.4 mg weekly. Design, Setting, and Participants: Randomized, double-blind, 68-week phase 3a withdrawal study conducted at 73 sites in 10 countries from June 2018 to March 2020 in adults with body mass index of at least 30 (or ≥27 with ≥1 weight-related comorbidity) and without diabetes. Interventions: A total of 902 participants received once-weekly subcutaneous semaglutide during run-in. After 20 weeks (16 weeks of dose escalation; 4 weeks of maintenance dose), 803 participants (89.0%) who reached the 2.4-mg/wk semaglutide maintenance dose were randomized (2:1) to 48 weeks of continued subcutaneous semaglutide (n = 535) or switched to placebo (n = 268), plus lifestyle intervention in both groups. Main Outcomes and Measures: The primary end point was percent change in body weight from week 20 to week 68; confirmatory secondary end points were changes in waist circumference, systolic blood pressure, and physical functioning (assessed using the Short Form 36 Version 2 Health Survey, Acute Version [SF-36]). Results: Among 803 study participants who completed the 20-week run-in period (with a mean weight loss of 10.6%) and were randomized (mean age, 46 [SD, 12] years; 634 [79%] women; mean body weight, 107.2 kg [SD, 22.7 kg]), 787 participants (98.0%) completed the trial and 741 (92.3%) completed treatment. With continued semaglutide, mean body weight change from week 20 to week 68 was -7.9% vs +6.9% with the switch to placebo (difference, -14.8 [95% CI, -16.0 to -13.5] percentage points; P < .001). Waist circumference (-9.7 cm [95% CI, -10.9 to -8.5 cm]), systolic blood pressure (-3.9 mm Hg [95% CI, -5.8 to -2.0 mm Hg]), and SF-36 physical functioning score (2.5 [95% CI, 1.6-3.3]) also improved with continued subcutaneous semaglutide vs placebo (all P < .001). Gastrointestinal events were reported in 49.1% of participants who continued subcutaneous semaglutide vs 26.1% with placebo; similar proportions discontinued treatment because of adverse events with continued semaglutide (2.4%) and placebo (2.2%). Conclusions and Relevance: Among adults with overweight or obesity who completed a 20-week run-in period with subcutaneous semaglutide, 2.4 mg once weekly, maintaining treatment with semaglutide compared with switching to placebo resulted in continued weight loss over the following 48 weeks. Trial Registration: ClinicalTrials.gov Identifier: NCT03548987.
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Claims the paper makes
65 Own result · 19 Not checked yet · 19 Own method · 12 Own interpretation · 2 Sources not found · 1 Partly supported · accuracy not yet measured
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“systolic blood pressure (-3.9 mm Hg [95% CI, -5.8 to -2.0 mm Hg])”
§ Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial > Abstract
plaindirectn = 803 ·- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“similar proportions discontinued treatment because of adverse events with continued semaglutide (2.4%) and placebo (2.2%).”
§ Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial > Abstract
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“with no change in diastolic blood pressure in either treatment group”
§ Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial > Confirmatory and Supportive Secondary End Points
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Gastrointestinal events were reported in 41.9% of participants who continued subcutaneous semaglutide vs 26.1% with placebo”
§ Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial > Abstract
plainn = 803- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Among 803 study participants who completed the 20-week run-in period (with a mean weight loss of 10.6%) and were randomized”
§ Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial > Abstract
plainn = 803- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“difference, -14.8 [95% CI, -16.0 to -13.5] percentage points; P < .001”
§ Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial > Abstract
plaindirectn = 803 ·- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“SF-36 physical functioning score (2.5 [95% CI, 1.6-3.3])also improved”
§ Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial > Abstract
plaindirectn = 803 ·- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Participant characteristics at randomization (week 20) were comparable between treatment groups”
§ Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial > Changes During the Run-in Period
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“BMI (difference, -4.7 [95% CI, -5.2 to -4.3]) decreased from week 20 to week 68 with continued semaglutide and increased with placebo”
§ Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial > Confirmatory and Supportive Secondary End Points
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Waist circumference (-9.7 cm [95% CI, -10.9 to -8.5 cm])”
§ Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial > Abstract
plaindirectn = 803 ·- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- It may state two separate claims as one. 47
- Probably not a substantial claim. 39
- The quote only partly states this claim. 1
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Sustained weight loss of a similar magnitude to that observed in this trial has been linked to improvements in obesityrelated complications, [25][26][27] such as type 2 diabetes, 28 with treatment guidelines recommending sustained weight loss of 5% to 15% for people with these conditions.5,6”
§ Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial > Discussion
What the sources say
- Partly supportedcites [25] 25. Singh M, Lee J, Gupta N, et al. Weight loss can lead to resolution of gastroesophageal reflux disease symptoms: a prospective intervention trial. Obesity (Silver Spring). 2013;21(2):284-290. doi: 10.1002/oby.20279 sourceExperimental — accuracy not yet measured
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Not checked yetcites [26] 26. Arterburn DE, Telem DA, Kushner RF, Courcoulas AP. Benefits and risks of bariatric surgery in adults: a review. JAMA. 2020;324(9): 879-887. doi:10.1001/jama.2020.12567 source
- Partly supportedcites [27] 27. Lean MEJ, Leslie WS, Barnes AC, et al. Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster-randomised trial. Lancet. 2018;391(10120): 541-551. doi:10.1016/S0140-6736(17)33102-1 sourceExperimental — accuracy not yet measured
Split into 2 atoms — 1 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 1 unverifiable. Expand the claim to see per-atom verdicts.
- Not checked yetcites [28] 28. Apovian CM, Garvey WT, Ryan DH. Challenging obesity: patient, provider, and expert perspectives on the roles of available and emerging nonsurgical therapies. Obesity (Silver Spring). 2015;23(suppl 2): S1-S26. doi:10.1002/oby.21140 source
- Not checked yetcites [5] 5. Garvey WT, Mechanick JI, Brett EM, et al; Reviewers of the AACE/ACE Obesity Clinical Practice Guidelines. American Association of Clinical Endocrinologists and American College of Endocrinology comprehensive clinical practice guidelines for medical care of patients with obesity. Endocr Pract. 2016;22(suppl 3):1-203. doi:10.4158/ EP161365.GL source
- Supportedcites [6] 6. Yumuk V, Tsigos C, Fried M, et al; Obesity Management Task Force of the European Association for the Study of Obesity. European guidelines for obesity management in adults. Obes Facts. 2015;8(6):402-424. doi:10.1159/000442721 source
Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“With continued semaglutide, mean body weight change from week 20 to week 68 was -7.9% vs +6.9% with the switch to placebo”
§ Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial > Abstract
plainn = 803- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Of the 504 participants who continued semaglutide and completed treatment, 89.5% received 2.4 mg at week 68, 4.0% received 1.7 mg, and 2.8% received less than 1.7 mg; data were missing for 3.8%.”
§ Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial > Study Participants
plainn = 504- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This was accompanied by reductions in waist circumference, BMI, systolic and diastolic blood pressure, hemoglobin A 1c , and fasting plasma glucose and improvements in lipid profiles”
§ Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial > Changes During the Run-in Period
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“787 participants (98.0%) completed the trial and 741 (92.3%) completed treatment.”
§ Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial > Abstract
plainn = 787- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Most (64.8%) had 1 to 3 comorbidities, with dyslipidemia and hypertension most prevalent”
§ Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial > Study Participants
plainn = 803- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“One participant who switched to placebo received rescue intervention (liraglutide) during the randomized period.No participants had bariatric surgery.”
§ Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial > Study Participants
plainSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“During the 20-week run-in, mean body weight declined by 10.6% to 96.1 kg (Table 1).”
§ Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial > Changes During the Run-in Period
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The quote only partly states this claim.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Among those not randomized at week 20 (n = 99 [11%]; Figure 1), mean body weight at week 0 (103.6 kg) was lower than in the randomized population; other characteristics were similar”
§ Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial > Study Participants
plainn = 99- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“most were female (79.0%) and White (83.7%), with a mean age of 46.0 years, a mean body weight of 107.2 kg, a mean BMI of 38.4, and a mean waist circumference of 115.3 cm at week 0”
§ Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial > Study Participants
plainn = 803- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“From week 20 to week 68, systolic blood pressure remained stable with continued semaglutide and significantly increased with placebo”
§ Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial > Confirmatory and Supportive Secondary End Points
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“770 (95.9%) provided a body weight measurement at week 68”
§ Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial > Study Participants
plainn = 803- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“During the run-in period, 84.3% of participants reported adverse events, with gastrointestinal tract disorders reported by 71.4%”
§ Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial > Adverse Events and Tolerability
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Moderate acute pancreatitis was reported in 1 participant (during run-in), who recovered during the study.”
§ Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial > Adverse Events and Tolerability
plainSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The observed proportions of participants achieving 5% or more, 10% or more, 15% or more, and 20% or more body weight loss from week 0 to week 68 with continued semaglutide vs placebo were 88.7% vs 47.6%, 79.0% vs 20.4%, 63.7% vs 9.2%, and 39.6% vs 4.8%, respectively”
§ Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial > Changes Over the Entire Trial Period
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“During week 20 to week 68, continued semaglutide led to additional reductions in hemoglobin A 1c and fasting plasma glucose and improvements in lipid profile vs placebo”
§ Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial > Confirmatory and Supportive Secondary End Points
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“One death was reported in each treatment group during the randomized period, each considered unrelated to study treatment”
§ Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial > Adverse Events and Tolerability
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Most gastrointestinal events were mild to moderate in severity, and the majority of participants recovered without treatment discontinuation.”
§ Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial > Adverse Events and Tolerability
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“During the run-in, 5.3% of par-ticipants discontinued treatment because of adverse events, most of which were gastrointestinal tract disorders”
§ Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial > Adverse Events and Tolerability
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Constipation | 62 (11.6) | 75 | 13.8 | 17 (6.3) | 19 | 7.1”
§ Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial > Conclusions
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Headache | 41 (7.7) | 48 | 8.8 | 10 (3.7) | 10 | 3.8”
§ Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial > Conclusions
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Body weight, % change | -7.9 (-8.6 to -7.2) | 6.9 (5.8 to 7.9) | -14.8 (-16.0 to -13.5) | <.001”
§ Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial > Conclusions
plainn = 535 ·- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Acute pancreatitis | 0 | | | 0 | | |”
§ Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial > Conclusions
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Well-tolerated new therapies that can produce substantial, sustained weight loss, when used long term, are therefore needed.7,10”
§ Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial > Abstract
What the sources say
- Not checked yetcites [7] 7. Bray GA, Frühbeck G, Ryan DH, Wilding JP. Management of obesity. Lancet. 2016;387(10031): 1947-1956. doi:10.1016/S0140-6736(16)00271-3 source
- Not checked yetcites [10] 10. Kushner RF, Calanna S, Davies M, et al. Semaglutide 2.4 mg for the treatment of obesity: key elements of the STEP trials 1 to 5. Obesity (Silver Spring). 2020;28(6):1050-1061. doi:10.1002/oby. 22794 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence.
In the paper
“The calculation included assumed differences between treatment groups of 8.7 percentage points in body weight change, 5.8 cm in waist circumference change, 4 mm Hg in systolic blood pressure change, and 3.9 points in SF-36 physical functioning score change, based on data from the phase 2 trial of semaglutide for obesity.14”
§ Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial > Sample Size Calculation
What the sources say
- Not checked yetcites [14] 14. O'Neil PM, Birkenfeld AL, McGowan B, et al. Efficacy and safety of semaglutide compared with liraglutide and placebo for weight loss in patients with obesity: a randomised, double-blind, placebo and active controlled, dose-ranging, phase 2 trial. Lancet. 2018;392(10148):637-649. doi:10.1016/ S0140-6736(18)31773-2 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In those who continued semaglutide after randomization, weight loss achieved during the run-in period not only was sustained but continued, reaching a plateau at week 60 to week 68 and ultimately resulting in an estimated reduction of 17.4% over the entire trial.”
§ Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial > Discussion
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Continuous end points were assessed using a mixed model for repeated measurements (MMRM), with randomized treatment as a factor and baseline (week 20) end point value as a covariate, 10 all nested within visit.An unstructured covariance matrix for measurements within the same participant was used.”
§ Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial > Statistical Analysis
What the sources say
- Not checked yetcites [10] 10. Kushner RF, Calanna S, Davies M, et al. Semaglutide 2.4 mg for the treatment of obesity: key elements of the STEP trials 1 to 5. Obesity (Silver Spring). 2020;28(6):1050-1061. doi:10.1002/oby. 22794 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Results are reported for the treatment policy estimand unless stated otherwise.Exploratory data and data from the run-in period (weeks 0-20) are summarized by descriptive statistics only.”
§ Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial > Statistical Analysis
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Participants receiving semaglutide, 2.4 mg, at week 20 were randomized in a 2:1 ratio using a blocking schema (block size of 6) in a double-blind manner, via an interactive web-based response system”
§ Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial > Procedures
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Subcutaneous semaglutide is a glucagon-like peptide 1 (GLP-1) receptor agonist approved for the treatment of type 2 diabetes at doses of 1.0 mg or less once weekly.11”
§ Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial > Abstract
What the sources say
- Not matchedcites [11] 11. US Food and Drug Administration. Ozempic (semaglutide): prescribing information. Revised January 2020. Accessed July 22, 2020. https:// www.accessdata.fda.gov/drugsatfda_docs/label/ 2020/209637s003lbl.pdf
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Not matched
None of the sources cited for this claim have been checked yet.
In the paper
“Proposed to be more clinically convenient, weekly administration was supported by a tolerability trial and pharmacokinetic modeling.10,15”
§ Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial > Abstract
What the sources say
- Not checked yetcites [10] 10. Kushner RF, Calanna S, Davies M, et al. Semaglutide 2.4 mg for the treatment of obesity: key elements of the STEP trials 1 to 5. Obesity (Silver Spring). 2020;28(6):1050-1061. doi:10.1002/oby. 22794 source
- Not checked yetcites [15] 15. Lingvay I, Desouza CV, Lalic KS, et al. A 26-week randomized controlled trial of semaglutide once daily versus liraglutide and placebo in patients with type 2 diabetes suboptimally controlled on diet and exercise with or without metformin. Diabetes Care. 2018;41(9):1926-1937. doi:10.2337/dc17-2381 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Continuous end points were analyzed using analysis of covariance, with randomized treatment as a factor and baseline (week 20) end point value as a covariate.”
§ Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial > Statistical Analysis
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The significant and sustained weight loss demonstrated with continued semaglutide in this study was accompanied by sustained improvement in waist circumference, lipid profiles, and glucose metabolism, all of which are cardiometabolic risk factors.”
§ Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial > Discussion
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These results emphasize the chronicity of obesity and the need for treatments that can maintain and maximize weight loss.”
§ Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial > Discussion
plain- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence. It may state two separate claims as one.
In the paper
“with the GLP-1 receptor agonist liraglutide, at a 3.0-mg/d dosage, which is approved for weight management, weight losses of 10% or more and 15% or more were achieved by 33% and 14%, respectively, among people treated for 56 weeks.30”
§ Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial > Discussion
What the sources say
- Not checked yetcites [30] 30. Wadden TA, Hollander P, Klein S, et al; NN8022-1923 Investigators. Weight maintenance and additional weight loss with liraglutide after low-calorie-diet-induced weight loss: the SCALE Maintenance randomized study. Int J Obes (Lond). 2013;37(11):1443-1451. doi:10.1038/ijo.2013.120 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“To account for the multicenter study design, a post hoc mixed-effects regression analysis of the primary end point was performed, with study site as a random effect.”
§ Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial > Statistical Analysis
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Continued semaglutide also produced significantly better outcomes for waist circumference, systolic blood pressure, and SF-36 physical functioning scores vs placebo.”
§ Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial > Discussion
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Cardiovascular events, acute pancreatitis events, and deaths were reviewed by an independent external event adjudication committee.”
§ Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial > Outcomes
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“The study was conducted according to the International Council for Harmonisation Good Clinical Practice Guideline and the Declaration of Helsinki 16 ; all participants provided written informed consent.”
§ Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial > Trial Design and Oversight
What the sources say
- Not matchedcites [16] 16. World Medical Association. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA. 2013;310(20):2191-2194.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“supporting its use for long-term treatment of obesity.”
§ Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial > Discussion
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“weight loss with liraglutide in clinical trials was of lesser magnitude and appeared to plateau earlier (at 20 weeks 31 or 40 weeks 30 ) than with semaglutide in the present trial (at 60-68 weeks).”
§ Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial > Discussion
What the sources say
- Not checked yetcites [31] 31. Hellström PM. GLP-1 analogue liraglutide as adjunct treatment in diabetes type 2 after failed bariatric/metabolic surgery. Ann Transl Med. 2019;7 (suppl 6):S240. doi:10.21037/atm.2019.08.94 source
- Not checked yetcites [30] 30. Wadden TA, Hollander P, Klein S, et al; NN8022-1923 Investigators. Weight maintenance and additional weight loss with liraglutide after low-calorie-diet-induced weight loss: the SCALE Maintenance randomized study. Int J Obes (Lond). 2013;37(11):1443-1451. doi:10.1038/ijo.2013.120 source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Given the modest efficacy of currently approved pharmacotherapies, [7][8][9] semaglutide may offer the potential to bridge the gap between behavioral and pharmacological options and bariatric surgery, which is currently considered the most effective and reliable intervention available for weight management.6,27,32”
§ Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial > Discussion
What the sources say
- Not checked yetcites [7] 7. Bray GA, Frühbeck G, Ryan DH, Wilding JP. Management of obesity. Lancet. 2016;387(10031): 1947-1956. doi:10.1016/S0140-6736(16)00271-3 source
- Not checked yetcites [8] 8. Bessesen DH, Van Gaal LF. Progress and challenges in anti-obesity pharmacotherapy. Lancet Diabetes Endocrinol. 2018;6(3):237-248. doi:10. 1016/S2213-8587(17)30236-X source
- Not checked yetcites [9] 9. Khera R, Murad MH, Chandar AK, et al. Association of pharmacological treatments for obesity with weight loss and adverse events: a systematic review and meta-analysis. JAMA. 2016; 315(22):2424-2434. doi:10.1001/jama.2016.7602 source
- Not checked yetcites [6] 6. Yumuk V, Tsigos C, Fried M, et al; Obesity Management Task Force of the European Association for the Study of Obesity. European guidelines for obesity management in adults. Obes Facts. 2015;8(6):402-424. doi:10.1159/000442721 source
- Not checked yetcites [27] 27. Lean MEJ, Leslie WS, Barnes AC, et al. Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster-randomised trial. Lancet. 2018;391(10120): 541-551. doi:10.1016/S0140-6736(17)33102-1 source
- Not checked yetcites [32] 32. Schauer PR, Kashyap SR, Wolski K, et al. Bariatric surgery versus intensive medical therapy in obese patients with diabetes. N Engl J Med. 2012; 366(17):1567-1576. doi:10.1056/NEJMoa1200225 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Sustained weight loss of 5% to 15% is advised to improve many conditions associated with overweight/obesity, with adjunctive pharmacotherapy recommended to help achieve this goal.5,6”
§ Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial > Abstract
What the sources say
- Not checked yetcites [5] 5. Garvey WT, Mechanick JI, Brett EM, et al; Reviewers of the AACE/ACE Obesity Clinical Practice Guidelines. American Association of Clinical Endocrinologists and American College of Endocrinology comprehensive clinical practice guidelines for medical care of patients with obesity. Endocr Pract. 2016;22(suppl 3):1-203. doi:10.4158/ EP161365.GL source
- Not checked yetcites [6] 6. Yumuk V, Tsigos C, Fried M, et al; Obesity Management Task Force of the European Association for the Study of Obesity. European guidelines for obesity management in adults. Obes Facts. 2015;8(6):402-424. doi:10.1159/000442721 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“adults with obesity/overweight who continued once-weekly treatment with subcutaneous semaglutide, 2.4 mg, had ongoing and persistent weight loss vs participants who switched to placebo, who gained weight.”
§ Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial > Discussion
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“assuming a 5% permanent discontinuation rate from week 20 to week 68 and available data for 60% of these participants at week 68”
§ Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial > Sample Size Calculation
plainn = 750- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“This trial was a 68-week, randomized, double-blind, placebocontrolled withdrawal study conducted at 73 sites in 10 countries”
§ Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial > Trial Design and Oversight
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“This dose, which is greater than what is currently approved for type 2 diabetes, was chosen based on a phase 2 clinical trial, in which greater weight loss was seen with once-daily semaglutide, 0.4 mg (equal to 2.8 mg/wk), vs current approved medical therapy.14”
§ Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial > Abstract
What the sources say
- Not checked yetcites [14] 14. O'Neil PM, Birkenfeld AL, McGowan B, et al. Efficacy and safety of semaglutide compared with liraglutide and placebo for weight loss in patients with obesity: a randomised, double-blind, placebo and active controlled, dose-ranging, phase 2 trial. Lancet. 2018;392(10148):637-649. doi:10.1016/ S0140-6736(18)31773-2 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Onceweekly subcutaneous semaglutide, 2.4 mg, is being investigated for the treatment of overweight/obesity in the global phase 3 Semaglutide Treatment Effect in People With Obesity (STEP) program.10”
§ Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial > Abstract
What the sources say
- Not checked yetcites [10] 10. Kushner RF, Calanna S, Davies M, et al. Semaglutide 2.4 mg for the treatment of obesity: key elements of the STEP trials 1 to 5. Obesity (Silver Spring). 2020;28(6):1050-1061. doi:10.1002/oby. 22794 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Short-term treatment (3-6 months) fails to produce long-term health benefits, 5 while several agents also have safety concerns.[7][8][9]”
§ Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial > Abstract
What the sources say
- Not checked yetcites [5] 5. Garvey WT, Mechanick JI, Brett EM, et al; Reviewers of the AACE/ACE Obesity Clinical Practice Guidelines. American Association of Clinical Endocrinologists and American College of Endocrinology comprehensive clinical practice guidelines for medical care of patients with obesity. Endocr Pract. 2016;22(suppl 3):1-203. doi:10.4158/ EP161365.GL source
- Not checked yetcites [7] 7. Bray GA, Frühbeck G, Ryan DH, Wilding JP. Management of obesity. Lancet. 2016;387(10031): 1947-1956. doi:10.1016/S0140-6736(16)00271-3 source
- Not checked yetcites [8] 8. Bessesen DH, Van Gaal LF. Progress and challenges in anti-obesity pharmacotherapy. Lancet Diabetes Endocrinol. 2018;6(3):237-248. doi:10. 1016/S2213-8587(17)30236-X source
- Not checked yetcites [9] 9. Khera R, Murad MH, Chandar AK, et al. Association of pharmacological treatments for obesity with weight loss and adverse events: a systematic review and meta-analysis. JAMA. 2016; 315(22):2424-2434. doi:10.1001/jama.2016.7602 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Maintaining long-term weight loss is challenging because of metabolic adaptation 2 and the difficulty of adhering to lifestyle interventions, 3 with weight regain often following weight loss.4”
§ Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial > Abstract
What the sources say
- Not checked yetcites [2] 2. Leibel RL, Seeley RJ, Darsow T, Berg EG, Smith SR, Ratner R. Biologic responses to weight loss and weight regain: report from an American Diabetes Association research symposium. Diabetes. 2015; 64(7):2299-2309. doi:10.2337/db15-0004 source
- Not checked yetcites [3] 3. Lemstra M, Bird Y, Nwankwo C, Rogers M, Moraros J. Weight loss intervention adherence and factors promoting adherence: a meta-analysis. Patient Prefer Adherence. 2016;10:1547-1559. doi: 10.2147/PPA.S103649 source
- Not checked yetcites [4] 4. Kroeger CM, Hoddy KK, Varady KA. Impact of weight regain on metabolic disease risk: a review of human trials. J Obes. 2014;2014:614519. doi:10. 1155/2014/614519 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Weight loss with semaglutide is believed to stem from improved appetite control, and consequent reduced energy intake, via effects in the hypothalamus and area postrema of the brain. 12,13”
§ Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial > Abstract
What the sources say
- Not matchedcites [12] 12. Friedrichsen M, Breitschaft A, Tadayon S, Wizert A, Skovgaard D. The effect of semaglutide 2.4 mg once weekly on energy intake, appetite, control of eating, and gastric emptying in adults with obesity. Diabetes Obes Metab. 2021;23(3):754-762. doi:10. 1111/dom.14280
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not checked yetcites [13] 13. Gabery S, Salinas CG, Paulsen SJ, et al. Semaglutide lowers body weight in rodents via distributed neural pathways. JCI Insight. 2020;5(6): e133429. doi:10.1172/jci.insight.133429 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Participants eligible for randomization at week 20 had to have attained the target maintenance dose of semaglutide (2.4 mg once weekly) by week 16 and have continued taking this dose until week 20.”
§ Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial > Participants
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“A multiple imputation approach 21 was used in which missing data were imputed from week 68 measurements from participants in the same treatment group.One thousand complete data sets were generated and analyzed, and the results were combined using the Rubin formula 22”
§ Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial > Statistical Analysis
What the sources say
- Not matchedcites [21] 21. Little RJA, Rubin DB. Statistical Analysis With Missing Data. John Wiley & Sons; 1987.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not checked yetcites [22] 22. Sjöström L, Rissanen A, Andersen T, et al; European Multicentre Orlistat Study Group. Randomised placebo-controlled trial of orlistat for weight loss and prevention of weight regain in obese patients. Lancet. 1998;352(9123):167-172. doi:10.1016/S0140-6736(97)11509-4 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
- Not matched
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Two further estimands (the tertiary and quaternary estimands) addressing treatment effects between week 0 and week 68 were also included.The tertiary estimand was identical to the primary treatment policy estimand, and the quaternary estimand was identical to the secondary trial product estimand, except values at week 20 (baseline) were replaced by those at week 0 (start of run-in) in the respect”
§ Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial > Statistical Analysis
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“To lessen any potential effect of the long half-life of semaglutide on adverse event reporting, adverse events were counted only during the randomized period if onset was after randomization.”
§ Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial > Limitations
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Because of the potential for type I error due to multiple comparisons, findings for analyses of supportive secondary end points should be interpreted as exploratory.”
§ Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial > Statistical Analysis
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The run-in period, as well as the trial setting, likely resulted in a study population who was both more tolerant of semaglutide and more adherent to medication use than would be the case in a typical setting.”
§ Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial > Limitations
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Second, there was no assessment of adherence to lifestyle interventions.”
§ Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial > Limitations
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Additional strengths of the study include the large sample size, blinded design, and high rates of treatment regimen and trial completion.”
§ Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial > Discussion
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“All results from statistical analyses were accompanied by 2-sided 95% confidence intervals and corresponding P values (statistical significance defined as P < .05).”
§ Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial > Statistical Analysis
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“For the analysis of participants who gained weight, the MMRM (with baseline body weight in kilograms as the covariate) was used to classify participants according to whether they gained weight or not.This classification was then analyzed using logistic regression, with the same factor and covariate as the MMRM.”
§ Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial > Statistical Analysis
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Third, while the withdrawal design is a strength, it can also result in selection bias and favorable carryover effects to the randomized period, potentially resulting in overestimation of weight loss with continued semaglutide compared with what would be expected in a typical individual.”
§ Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial > Limitations
plainconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The high treatment and trial completion rates were likely a result of multiple factors, including a focus on participant retention, selection of a population who could tolerate semaglutide during run-in, and inclusion of participants who had previously attempted to lose weight and so were likely motivated to continue in the trial following weight loss in the run-in period.”
§ Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial > Discussion
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Additional strengths of the study include the large sample size, blinded design, and high rates of treatment regimen and trial completion.”
§ Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial > Discussion
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Although a higher maintenance dosage of semaglutide (2.4 mg/wk) was used in this trial, the adverse event profile and tolerability were consistent with data from a phase 2 study in people with obesity 14 and semaglutide trials in patients with type 2 diabetes using lower maintenance dosages (up to 1.0 mg/wk), 34 as well as with that reported for other GLP-1 receptor agonists, 35 with no new concer”
§ Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial > Discussion
What the sources say
- Not checked yetcites [14] 14. O'Neil PM, Birkenfeld AL, McGowan B, et al. Efficacy and safety of semaglutide compared with liraglutide and placebo for weight loss in patients with obesity: a randomised, double-blind, placebo and active controlled, dose-ranging, phase 2 trial. Lancet. 2018;392(10148):637-649. doi:10.1016/ S0140-6736(18)31773-2 source
- Not matchedcites [34] 34. Trujillo J. Safety and tolerability of once-weekly GLP-1 receptor agonists in type 2 diabetes. J Clin Pharm Ther. 2020;45(suppl 1):43-60. doi:10.1111/ jcpt.13225
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [35] 35. US Food and Drug Administration. Enrichment Strategies for Clinical Trials to Support Determination of Effectiveness of Human Drugs and Biological Products: Guidance for Industry. Published March 2019. Accessed July 22, 2020. https://www.fda.gov/regulatory-information/ search-fda-guidance-documents/enrichment- strategies-clinical-trials-support-approval-human- drugs-and-biological-products
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper relies on this without support.
Before this trial, the effect of continuing versus withdrawing semaglutide on weight loss maintenance in people with overweight or obesity was unknown.
“The effect of continuing vs withdrawing treatment with semaglutide, a glucagon-like peptide 1 receptor agonist, on weight loss maintenance in people with overweight or obesity is unknown.”
The authors state this as an assumption.
For the trial product estimand, participants are assumed to have continued randomized treatment for the planned study duration without medication discontinuation or rescue interventions between week 20 and week 68.
“The trial product estimand (the secondary estimand) quantified the average treatment effect modeled to assume participants continued taking randomized treatment for the planned study duration without medication discontinuation or rescue interventions between week 20 and week 68.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source doesn’t support the claim as written.
In the citing paper
“If treatment with incretin-based medications is discontinued, bodyweight will increase at approximately the velocity as it had been lost with treatment.”
From GLP-1 receptor agonists and next-generation incretin-based medications: metabolic, cardiovascular, and renal benefits (2026) · cites this paper as [64]
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredThe cited source doesn’t support the claim as written.
In the citing paper
“If treatment with incretin-based medications is discontinued, bodyweight will increase at approximately the velocity as it had been lost with treatment. [64][65]5][66]”
From GLP-1 receptor agonists and next-generation incretin-based medications: metabolic, cardiovascular, and renal benefits (2026) · cites this paper as [64]
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredThe cited source doesn’t support the claim as written.
In the citing paper
“In the semaglutide treatment effect in people (STEP) with obesity trials, semaglutide 2.4 mg weekly produced a mean placebo-adjusted weight loss of 14.9% over 68 weeks in STEP 1, and up to 16.0% in STEP 4 with continued use [6,8].”
From Obesity: Clinical Impact, Pathophysiology, Complications, and Modern Innovations in Therapeutic Strategies (2025) · cites this paper as [8]
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In 3 studies of 56-week duration involving persons with obesity and dyslipidemia or hypertension, weight loss ranged from 6.2% to 8.0% with 3 mg liraglutide vs 0.2% to 2.9% with placebo.754–756”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [755]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“For both semaglutide and tirzepatide, continuing the drug was associated with additional weight loss and stopping was associated with weight regain and recidivism of health benefits.”
From New drugs for the treatment of obesity: do we need approaches to preserve muscle mass? (2025) · cites this paper as [23]
Experimental — accuracy not yet measured
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In the first of the STEP trials (STEP 1–4), 68 weeks of once-weekly s.c. semaglutide 2.4 mg treatment resulted in mean weight loss of 15%–17% in adults with overweight or obesity and 10% in those who also had type 2 diabetes.13, 14, 15, 16”
From Effects of once-weekly semaglutide 2.4 mg on C-reactive protein in adults with overweight or obesity (STEP 1, 2, and 3): exploratory analyses of three randomised, double-blind, placebo-controlled, phase 3 trials (2023) · cites this paper as [16]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In STEP-4, the rebound in HDL-C after cessation is attributed to the lipid-lowering effect of semaglutide.17”
From Metabolic rebound after GLP-1 receptor agonist discontinuation: a systematic review and meta-analysis (2025) · cites this paper as [17]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Yet, these breakthroughs are not without challenges, including high costs, accessibility barriers, and concerns over long-term safety and weight regain upon discontinuation [8].”
From Obesity: Clinical Impact, Pathophysiology, Complications, and Modern Innovations in Therapeutic Strategies (2025) · cites this paper as [8]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The STEP 1, 2, 3, and 4 trials demonstrated that semaglutide 2.4 mg compared with placebo, as adjunct to lifestyle management or intensive behavioral therapy, led to mean weight losses of 6–15% in participants with and without type 2 diabetes (14,18–20).”
From Effects of semaglutide on albuminuria and kidney function in people with overweight or obesity with or without type 2 diabetes: exploratory analysis from the STEP 1, 2, and 3 trials (2023) · cites this paper as [20]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“However, clinical obesity trials with off-medication phases have not previously assessed fat mass.18,19,34,35”
From Healthy weight loss maintenance with exercise, GLP-1 receptor agonist, or both combined followed by one year without treatment: a post-treatment analysis of a randomised placebo-controlled trial (2024) · cites this paper as [18]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Individualized titration schedules, reassurance about symptom transience, and short-term symptomatic therapy can maintain adherence and limit discontinuation to below 5–7% once maintenance dosing is achieved [6,11,12,13].”
From Gastrointestinal Adverse Effects of Anti-Obesity Medications in Non-Diabetic Adults: A Systematic Review (2025) · cites this paper as [6]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Current evidence from trials suggests that weight is regained rapidly for patients who discontinue GLP‐1RA treatment, 127 , 128 , 129”
From Real‐world evidence on the utilization, clinical and comparative effectiveness, and adverse effects of newer GLP ‐ 1RA ‐based weight‐loss therapies (2025) · cites this paper as [128]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“This approval was based on the Semaglutide Treatment Effect in People with Obesity (STEP) clinical trial programme, which demonstrated significant weight reduction, improvement of cardiometabolic factors, and positive patient-reported outcomes. 16 -20”
From Efficacy and safety of semaglutide 2.4 mg for weight loss in overweight or obese adults without diabetes: An updated systematic review and meta‐analysis including the 2‐year STEP 5 trial (2024) · cites this paper as [18]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The findings from three studies (n = 3375) 16 -18 showed that semaglutide induced a more significant enhancement in health-related quality of life compared to placebo. This improvement was evidenced by the higher SF-36 physical functioning score (MD:1.75 [95% CI 0.92, 2.58]; P < 0.0001 [Figure S11]).”
From Efficacy and safety of semaglutide 2.4 mg for weight loss in overweight or obese adults without diabetes: An updated systematic review and meta‐analysis including the 2‐year STEP 5 trial (2024) · cites this paper as [18]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“the semaglutide groups demonstrated a significant reduction in weight at the end of the treatment period for various steps, namely, 14.9% for STEP 1, 16% for STEP 3, 17.4% for STEP 4, 15.2% for STEP 5, and 15.8% for STEP 8.”
From Efficacy and safety of semaglutide 2.4 mg for weight loss in overweight or obese adults without diabetes: An updated systematic review and meta‐analysis including the 2‐year STEP 5 trial (2024) · cites this paper as [18]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“weight regain was observed following the discontinuation of semaglutide in both the STEP 4 withdrawal trial (after 20 weeks of treatment) and the STEP 1 off-treatment extension study (after 68 weeks of treatment).”
From Efficacy and safety of semaglutide 2.4 mg for weight loss in overweight or obese adults without diabetes: An updated systematic review and meta‐analysis including the 2‐year STEP 5 trial (2024) · cites this paper as [18]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In phase 3 trials, women aged ≥ 65 years achieved sustained weight loss of 10–20%, with consistent cardiometabolic improvements.”
From A Narrative Review on GLP-1 Receptor Agonists for Obesity in Older Women: Maximizing Weight Loss While Preserving Lean Mass (2026) · cites this paper as [38]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Two major trial programs, the STEP program for semaglutide [35,36,37,38,39] and the SURMOUNT trials [40,41,42,43] for tirzepatide, offer critical insights into the benefits of these therapies in older populations.”
From A Narrative Review on GLP-1 Receptor Agonists for Obesity in Older Women: Maximizing Weight Loss While Preserving Lean Mass (2026) · cites this paper as [38]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Despite this attenuation, the improvements observed in metabolic parameters, such as HbA1c (glycated hemoglobin), blood pressure, and lipid profiles, were significant.”
From A Narrative Review on GLP-1 Receptor Agonists for Obesity in Older Women: Maximizing Weight Loss While Preserving Lean Mass (2026) · cites this paper as [38]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In the STEP 4 and SURMOUNT 4 trials, switching from initial active treatments to placebo also led to a relapse in important cardiovascular risk markers such as Hba1c, SBP, and low-density lipoprotein (LDL)-cholesterol.”
From The societal implications of using glucagon-like peptide-1 receptor agonists for the treatment of obesity (2025) · cites this paper as [19]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“When GLP‐1s are discontinued, weight regain is common—with up to two‐thirds of the lost weight regained within 1 years [18, 19, 20].”
From Nutritional priorities to support GLP ‐1 therapy for obesity: A joint Advisory from the American College of Lifestyle Medicine, the American Society for Nutrition, the Obesity Medicine Association, and The Obesity Society (2025) · cites this paper as [19]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“There is also evidence that antiobesity medications, including long-acting glucagon-like peptide-1 (GLP-1) receptor agonists, naltrexone/bupropion, phentermine/topiramate, and orlistat, may help maintenance of achieved weight reduction.5,7,8,9,10,11,12”
From Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT-4 Randomized Clinical Trial (2024) · cites this paper as [5]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“two-thirds of lost weight is typically regained within a year of discontinuation”
From Weight maintenance after discontinuation of GLP-1 therapies (2026) · cites this paper as [8]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“most patients experience rapid weight regain”
From Weight maintenance after discontinuation of GLP-1 therapies (2026) · cites this paper as [8]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In STEP-4, after a 20-week run-in with semaglutide led to a 10.6% mean weight loss, those who switched to placebo regained 6.9% of baseline weight (roughly 65% of prior loss)”
From Weight maintenance after discontinuation of GLP-1 therapies (2026) · cites this paper as [8]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In the STEP 4 trial, participants completed 20 weeks of semaglutide treatment and were transitioned to placebo for an additional 48 weeks.96 Mean weight regain was 6.9% of lost weight during the placebo administration.96”
From Obesity Management in Adults: A Review (2023) · cites this paper as [96]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In the STEP 1 extension, weight regain was comparatively rapid following semaglutide withdrawal compared with that seen in other obesity pharmacotherapy withdrawal trials, including after semaglutide withdrawal in STEP 4.”
From Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension (2022) · cites this paper as [13]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“A prior trial (STEP 4) assessed the effects of semaglutide withdrawal, with participants initially receiving 20 weeks of semaglutide 2.4 mg treatment during a run‐in period, followed by randomization to continued semaglutide treatment or withdrawal (switch to placebo) for an additional 48 weeks, with lifestyle intervention throughout. 13”
From Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension (2022) · cites this paper as [13]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“noted superiority over other GLP-1RAs.”
From Semaglutide for the treatment of antipsychotic-associated weight gain in patients not responding to metformin – a case series (2023) · cites this paper as [29]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The approach of stopping medication after intentional weight loss can lead to weight cycling and loss of improvements in cardiometabolic health such as increased insulin resistance or blood pressure, as is seen when individuals stop therapy in other chronic diseases such as hypertension and dyslipidemia3,15,16.”
From Orforglipron for maintenance of body weight reduction: the double-blind, randomized phase 3b ATTAIN-MAINTAIN trial (2026) · cites this paper as [16]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“The extent of bodyweight reduction is highly variable between individuals,”
From GLP-1 receptor agonists and next-generation incretin-based medications: metabolic, cardiovascular, and renal benefits (2026) · cites this paper as [64]
The cited source says what the claim attributes to it.
In the citing paper
“an initial 20-week Sema (2.4 mg) administration reduced body weight by 10.6% (À11.1 kg) (82).Thereafter, an additional body weight reduction of 7.9% (À7.1 kg) was reported for those maintained on Sema treatment until 68 weeks, whereas the group that discontinued treatment at 20 weeks demonstrated body weight regain of 6.9% (6.1 kg) (82).”
From Incretin-Based Weight Loss Pharmacotherapy: Can Resistance Exercise Optimize Changes in Body Composition? (2024) · cites this paper as [82]
The cited source says what the claim attributes to it.
In the citing paper
“The extent of bodyweight reduction is highly variable between individuals, 64,[67][68][69]”
From GLP-1 receptor agonists and next-generation incretin-based medications: metabolic, cardiovascular, and renal benefits (2026) · cites this paper as [64]
The cited source says what the claim attributes to it.
In the citing paper
“Studies in adults with overweight or obesity suggest that withdrawing treatment with semaglutide leads to increases in body weight (131), highlighting the chronic nature of, and need for, obesity/weight management.”
The cited source says what the claim attributes to it.
In the citing paper
“Randomized withdrawal studies of antiobesity medications to date have consistently demonstrated clinically significant body weight regain with cessation of therapy.5,6”
From Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT-4 Randomized Clinical Trial (2024) · cites this paper as [5]
The cited source says what the claim attributes to it.
In the citing paper
“These results suggest that long-term use is necessary.96,100”
From Obesity Management in Adults: A Review (2023) · cites this paper as [96]
The cited source says what the claim attributes to it.
In the citing paper
“After cessation of semaglutide, participants regained significant amounts of weight.96,100”
From Obesity Management in Adults: A Review (2023) · cites this paper as [96]
The cited source says what the claim attributes to it.
In the citing paper
“Both the STEP-4 [128] and SURMOUNT-4 [129] studies showed that after 20 weeks of pharmacological treatment with semaglutide and after 36 weeks with tirzepatide, respectively, people with obesity tended to regain weight if the pharmacological treatment was stopped.”
From Nutrition and Physical Activity in Optimizing Weight Loss and Lean Mass Preservation in the Incretin-Based Medications Era: A Narrative Review (2025) · cites this paper as [128]
The cited source says what the claim attributes to it.
In the citing paper
“Weight regain has previously been observed following withdrawal of obesity pharmacotherapies, including orlistat and lorcaserin—and also semaglutide, as shown in STEP 4—despite continued lifestyle intervention.”
From Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension (2022) · cites this paper as [13]
The cited source says what the claim attributes to it.
In the citing paper
“Long‐term obesity pharmacotherapy may be required for weight maintenance, as cessation of pharmacological treatment is frequently followed by weight regain, even with continued lifestyle intervention. 13 , 14 , 15”
From Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension (2022) · cites this paper as [13]
The cited source says what the claim attributes to it.
In the citing paper
“The weight regain data seen in STEP 4 (36) and the STEP 1 extension study (38), where participants discontinue active medication, strongly suggest that pharmacological treatment must be sustained to combat the adaptive physiological forces that hinder long-term weight reduction (39).”
From New Frontiers in Obesity Treatment: GLP-1 and Nascent Nutrient-Stimulated Hormone-Based Therapeutics (2023) · cites this paper as [36]
The cited source says what the claim attributes to it.
In the citing paper
“the recently approved 2.4 mg dose of once-weekly GLP-1R agonist semaglutide (Wegovy) increases mean weight reduction in this population to 15–20% [[5], [6], [7], [8]]”
From Next generation GLP-1/GIP/glucagon triple agonists normalize body weight in obese mice (2022) · cites this paper as [7]
The cited source says what the claim attributes to it.
In the citing paper
“Generally, approximately 15% weight loss was observed in overweight and obese, non-diabetic adults across various treatment periods, lasting up to 2 years (from STEP-1 to STEP-6, STEP-8) [72,73,74,75,76,77,78,79].”
From New Developments in Pharmacological Treatment of Obesity and Type 2 Diabetes—Beyond and within GLP-1 Receptor Agonists (2024) · cites this paper as [75]
The cited source says what the claim attributes to it.
In the citing paper
“From week 20 to week 68, participants who discontinued the drug regained an average of 6.9% of their baseline body weight, while those who continued treatment lost an additional 7.9%.6”
From The expanding role of GLP-1 receptor agonists: a narrative review of current evidence and future directions (2025) · cites this paper as [6]
The cited source says what the claim attributes to it.
In the citing paper
“In STEP 4 and SURMOUNT 4, participants switching to placebo treatment after 20 weeks of semaglutide or 36 weeks of tirzepatide treatment, respectively, gradually regained weight despite ongoing behavioral support, whereas those who continued active treatments continued to lose weight.”
From The societal implications of using glucagon-like peptide-1 receptor agonists for the treatment of obesity (2025) · cites this paper as [19]
The cited source says what the claim attributes to it.
In the citing paper
“Notably, this has been observed even with accompanying use of conventional nutritional counseling and/or behavioral therapy [18, 19].”
The cited source says what the claim attributes to it.
In the citing paper
“Switching to placebo after 20 weeks of semaglutide treatment resulted in a weight regain of 6.9% body weight in contrast to a weight reduction of 7.9% body weight with continuous semaglutide treatment at week 68, despite monthly recommendations of calorie-reduced diet and increased physical activity.18”
The cited source says what the claim attributes to it.
In the citing paper
“At least 5 trials (including the present study) across various classes of medications, including potent antiobesity medications such as semaglutide, have demonstrated that weight is substantially regained after cessation of pharmacotherapy.5,6,23,24”
From Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT-4 Randomized Clinical Trial (2024) · cites this paper as [5]
The cited source says what the claim attributes to it.
In the citing paper
“while those who continued semaglutide lost a further 7.9% over a year”
From Weight maintenance after discontinuation of GLP-1 therapies (2026) · cites this paper as [8]
The cited source says what the claim attributes to it.
In the citing paper
“Following a 20 week run-in on semaglutide, the STEP 4 trial randomized participants to remain on study drug versus placebo until week 68.Those who remained on active drug lost an additional 8% of their body weight, while those on placebo regained 7%, for a final difference between groups of 15% body weight.156”
From Effectiveness and safety of drugs for obesity (2024) · cites this paper as [156]
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Evidence has suggested that the experience of adverse gastrointestinal events is not significantly related to the amount of weight reduction achieved [26,27].”
From Nutritional considerations with antiobesity medications (2024) · cites this paper as [27]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“On average, weight loss in this age group ranged from 10–15%, with a slight attenuation of this effect in participants aged over 70 years.”
From A Narrative Review on GLP-1 Receptor Agonists for Obesity in Older Women: Maximizing Weight Loss While Preserving Lean Mass (2026) · cites this paper as [38]
Experimental — accuracy not yet measuredIn the citing paper
“Weight regain is typically observed after withdrawal of pharmacotherapy, even with continued lifestyle intervention, as shown in withdrawal randomized clinical trials of obesity management medications.5,6,7”
From Cardiometabolic Parameter Change by Weight Regain on Tirzepatide Withdrawal in Adults With Obesity: A Post Hoc Analysis of the SURMOUNT-4 Trial (2026) · cites this paper as [6]
In the citing paper
“these findings support the importance of long-term maintenance of weight reduction through lifestyle intervention and obesity management medications to sustain cardiometabolic benefits and improved health-related quality of life.”
From Cardiometabolic Parameter Change by Weight Regain on Tirzepatide Withdrawal in Adults With Obesity: A Post Hoc Analysis of the SURMOUNT-4 Trial (2026) · cites this paper as [6]
In the citing paper
“withdrawal of tirzepatide led to most participants regaining weight despite continued lifestyle intervention”
From Cardiometabolic Parameter Change by Weight Regain on Tirzepatide Withdrawal in Adults With Obesity: A Post Hoc Analysis of the SURMOUNT-4 Trial (2026) · cites this paper as [6]
In the citing paper
“The study uses standard‐of‐care preventive measures along with semaglutide 2.4 mg subcutaneous once‐weekly treatment, which has been demonstrated to provide significant and sustained mean weight loss of up to 16% [10, 11, 12, 13, 24, 25], significant CV risk factor improvements, and proven CV benefit in patients with diabetes and prior CV events [16, 26].”
From Semaglutide for cardiovascular event reduction in people with overweight or obesity: SELECT study baseline characteristics (2023) · cites this paper as [24]
In the citing paper
“The STEP trial programme assessed the effect of a high dose of the GLP-1RA semaglutide (2.4 mg once weekly by subcutaneous injection: Weygovy ) and typically noted about a 15% reduction in body weight during treatment periods up to 2 years in overweight and obese adults who did not have T2DM (STEP-1, 3, 4, 5, 8) [16-23].”
From Recent advances in peptide-based therapies for obesity and type 2 diabetes (2024) · cites this paper as [19]
In the citing paper
“Both efficacy benchmark criteria for weight management products were met in STEP 1, 3, 4 and 8 trials [15–17, 19].”
From Efficacy of GLP-1 RA Approved for Weight Management in Patients With or Without Diabetes: A Narrative Review (2022) · cites this paper as [17]
In the citing paper
“Semaglutide resulted in 10.3–17.4% difference in mean weight compared to placebo [15–17, 19].”
From Efficacy of GLP-1 RA Approved for Weight Management in Patients With or Without Diabetes: A Narrative Review (2022) · cites this paper as [17]
In the citing paper
“The proportion of subjects who lost ≥ 5% of baseline body weight was 86.4–88.7% [15–17, 19].”
From Efficacy of GLP-1 RA Approved for Weight Management in Patients With or Without Diabetes: A Narrative Review (2022) · cites this paper as [17]
In the citing paper
“While the STEP 2 trail included 51% female participants [22], the STEP 1, STEP 3 and STEP 4 trials included 73%, 81% and 79% female participants, respectively [15–17]. Thus, STEP 2 has a greater proportion of men (49.1%) than the other trials (19.0–25.9%).”
From Efficacy of GLP-1 RA Approved for Weight Management in Patients With or Without Diabetes: A Narrative Review (2022) · cites this paper as [17]
In the citing paper
“The percentage of Caucasian participants in each study was 76%, 62%, 76% and 84% for the STEP 1–4 trials, respectively [15–17, 22].”
From Efficacy of GLP-1 RA Approved for Weight Management in Patients With or Without Diabetes: A Narrative Review (2022) · cites this paper as [17]
In the citing paper
“the main trials for which data have been published (STEP 1 through STEP 5, STEP 8, and STEP TEENS) did not include participants who reported having symptoms of major depressive disorder within 2 years before screening, which limits their ability to assess psychiatric adverse events in people with a recent history of depression [3,4,93,94,95,96,97].”
From What Is Food Noise? A Conceptual Model of Food Cue Reactivity (2023) · cites this paper as [95]
In the citing paper
“Evidence indicates that weight regain frequently occurs after discontinuation of anti-obesity medications [14]”
From Dietary and Behavioral Strategies for Weight Loss and Weight Loss Maintenance: A Narrative Review (2025) · cites this paper as [14]
In the citing paper
“Orlistat three-times daily [56][57][58][59] was found in long-term trials to have potential benefits for both weight (mean total loss ≈7%) and cardiovascular risk factors, but placebo-subtracted weight losses are ≈3% and side-effects such oily stools limit its use.60”
From Approach to Obesity Treatment in Primary Care: A Review (2024) · cites this paper as [59]
In the citing paper
“Several anti-obesity medications have been approved by the U.S. Food and Drug Administration (FDA), including orlistat, phentermine-topiramate, naltrexone-bupropion, liraglutide, semaglutide, and tirzepatide, while newer agents such as orforglipron and retatrutide continue to emerge through late-phase trials [2,3,4,5,6,7].”
From Gastrointestinal Adverse Effects of Anti-Obesity Medications in Non-Diabetic Adults: A Systematic Review (2025) · cites this paper as [6]
In the citing paper
“Multiple trials reported the most commonly observed AEs included nausea, diarrhea, constipation, and abdominal discomfort [3,6,9,12,13].”
From Gastrointestinal Adverse Effects of Anti-Obesity Medications in Non-Diabetic Adults: A Systematic Review (2025) · cites this paper as [6]
In the citing paper
“As measured from the start of the run-in period, the two groups achieved mean cumulative weight losses at week 68 of 17.4% and 5.7%, respectively (see Figures 2 and 3).”
From Semaglutide for the treatment of obesity (2023) · cites this paper as [37]
In the citing paper
“Those who remained on semaglutide lost 7.9 percentage points of their randomization weight from weeks 20 to 68, whereas those switched to placebo gained 6.9 percentage points (estimated treatment differences = −14.8; 95% CI=−16.0 to −13.5 percentage points; p<0.001).”
From Semaglutide for the treatment of obesity (2023) · cites this paper as [37]
In the citing paper
“These medications work through diverse mechanisms such as slowing of gastric emptying (GLP1 agonists), central sympathomimetic appetite suppression (phentermine), hypothalamic reward modulation (naltrexone/bupropion), and lipase inhibition (orlistat) [6,8,9,10,11].”
From Gastrointestinal Adverse Effects of Anti-Obesity Medications in Non-Diabetic Adults: A Systematic Review (2025) · cites this paper as [6]
In the citing paper
“Continued semaglutide, relative to the switch to placebo, was associated with better outcomes for waist circumference, systolic blood pressure, hemoglobin A1c, fasting plasma glucose, fasting serum insulin, lipid profile, and physical functioning on the SF-36 (Table 1).”
From Semaglutide for the treatment of obesity (2023) · cites this paper as [37]
In the citing paper
“Several anti-obesity medications have been approved by the U.S. Food and Drug Administration (FDA), including orlistat, phentermine-topiramate, naltrexone-bupropion, liraglutide, semaglutide, and tirzepatide, while newer agents such as orforglipron and retatrutide continue to emerge through late-phase trials [2,3,4,5,6,7].”
From Gastrointestinal Adverse Effects of Anti-Obesity Medications in Non-Diabetic Adults: A Systematic Review (2025) · cites this paper as [6]
In the citing paper
“Patients will need to understand that, following the first year of treatment, continued use of semaglutide will help them principally in maintaining their lost weight rather than in losing additional weight (which many will desire because they will still have excess weight).”
From Semaglutide for the treatment of obesity (2023) · cites this paper as [37]
In the citing paper
“Incretin-based therapies (semaglutide, liraglutide, exenatide) showed clear dose-dependent increase in nausea and diarrhea across both trials and real-world datasets [6,8,9,10,11].”
From Gastrointestinal Adverse Effects of Anti-Obesity Medications in Non-Diabetic Adults: A Systematic Review (2025) · cites this paper as [6]
In the citing paper
“The second finding concerns the relatively rapid weight regain that occurred in participants who were randomly assigned to discontinue medication after the 20-week run-in.”
From Semaglutide for the treatment of obesity (2023) · cites this paper as [37]
In the citing paper
“In STEP 4, diarrhea occurred in 14.4% of semaglutide-treated participants vs. 7.1% placebo, nausea 14.0% vs. 4.9%, and constipation 11.6% vs. 6.3%; discontinuation rates for GI events were 2.4% vs. 2.2%, respectively [6].”
From Gastrointestinal Adverse Effects of Anti-Obesity Medications in Non-Diabetic Adults: A Systematic Review (2025) · cites this paper as [6]
In the citing paper
“STEP 4 revealed two very important findings, the first which is that patients will lose substantial amounts of weight during the 16-week upward titration period but will not achieve their maximum weight loss until taking the full dose for 1 year.”
From Semaglutide for the treatment of obesity (2023) · cites this paper as [37]
In the citing paper
“Across all drug classes, the timing of GI AEs strongly implicates the dose-escalation phase as the key driver of intolerance [6,7,13].”
From Gastrointestinal Adverse Effects of Anti-Obesity Medications in Non-Diabetic Adults: A Systematic Review (2025) · cites this paper as [6]
In the citing paper
“GLP-1 receptor agonists (semaglutide, liraglutide, exenatide, orforglipron) consistently produced the highest frequency of GI events among approved pharmacotherapies [6,7,9,10,13].”
From Gastrointestinal Adverse Effects of Anti-Obesity Medications in Non-Diabetic Adults: A Systematic Review (2025) · cites this paper as [6]
In the citing paper
“Gallbladder-related events and rare pancreatitis cases were more frequently observed with GLP-1 based drugs, consistent with their known effects on biliary motility and lipid metabolism rather than direct pancreatic toxicity [4,6,13].”
From Gastrointestinal Adverse Effects of Anti-Obesity Medications in Non-Diabetic Adults: A Systematic Review (2025) · cites this paper as [6]
In the citing paper
“Gallbladder-related events and rare pancreatitis cases were more frequently observed with GLP-1 based drugs, consistent with their known effects on biliary motility and lipid metabolism rather than direct pancreatic toxicity [4,6,13].”
From Gastrointestinal Adverse Effects of Anti-Obesity Medications in Non-Diabetic Adults: A Systematic Review (2025) · cites this paper as [6]
In the citing paper
“For incretin-based agents, nausea and diarrhea are primarily mediated by delayed gastric emptying, activation of central satiety centers in the hypothalamus, and enhanced vagal signaling that collectively slow motility [4,6,8,11,13].”
From Gastrointestinal Adverse Effects of Anti-Obesity Medications in Non-Diabetic Adults: A Systematic Review (2025) · cites this paper as [6]
In the citing paper
“When GLP-1s are stopped, weight regain is common—typically nearly to baseline within one year [[18], [19], [20]].”
In the citing paper
“Across the phase 3 STEP program for semaglutide 2.4 mg s.c.weekly plus lifestyle modification in individuals living with obesity without T2D, the body weight reduction from baseline ranged from 12.1% to 18.2%.107-113”
From Management of type 2 diabetes, obesity, or nonalcoholic steatohepatitis with high‐dose GLP‐1 receptor agonists and GLP‐1 receptor‐based co‐agonists (2024) · cites this paper as [109]
In the citing paper
“When GLP-1s are discontinued, weight regain is common—with up to two-thirds of the lost weight regained within 1 y [[18], [19], [20]].”
In the citing paper
“Notably, this has been observed even with accompanying use of conventional nutritional counseling and/or behavioral therapy [18,19].”
In the citing paper
“During the subsequent 48 weeks, participants who remained on semaglutide lost an additional 7.9% body weight whereas the placebo group gained 6.9% body weight (36).”
From New Frontiers in Obesity Treatment: GLP-1 and Nascent Nutrient-Stimulated Hormone-Based Therapeutics (2023) · cites this paper as [36]
In the citing paper
“This is in contrast to what has been observed after medication discontinuation at the end of randomized trials [9, 23].”
From Changes in weight and glycemic control following obesity treatment with semaglutide or tirzepatide by discontinuation status (2025) · cites this paper as [23]
In the citing paper
“In the STEP 1-4 trials (semaglutide), the proportion of participants experiencing nausea increased from 0 to ~20% from Week 0 to Week 20 (dose escalation or run-in period), then decreased to ~4% by Week 68 (maintenance phase) [13,65,84,93,98].”
From Symptomatic Adverse Events and Quality of Life Related to Incretin-Based Medicines for Obesity: A Systematic Review Involving >400,000 Subjects (2025) · cites this paper as [84]
In the citing paper
“Common adverse effects include nausea, vomiting, diarrhea, constipation, early satiety, dyspepsia, hypodipsia, and anorexia [17,18].”
From Unintended Consequences of Obesity Pharmacotherapy: A Nutritional Approach to Ensuring Better Patient Outcomes (2025) · cites this paper as [17]
In the citing paper
“However, their mechanism of action, which includes delayed gastric emptying and reduction in appetite, can also give rise to poor nutritional intake.”
From Unintended Consequences of Obesity Pharmacotherapy: A Nutritional Approach to Ensuring Better Patient Outcomes (2025) · cites this paper as [17]
In the citing paper
“the FDA approved semaglutide in June 2021 for long-term weight management in overweight or people with obesity (31–33).”
From Gastrointestinal adverse events associated with semaglutide: A pharmacovigilance study based on FDA adverse event reporting system (2022) · cites this paper as [33]
In the citing paper
“In major trials assessing weight following cessation, namely STEP 1,6 STEP 411 and SURMOUNT-4,12 we noted that weight regain resembled an exponential recovery curve approaching an asymptote.”
From Trajectory of weight regain after cessation of GLP-1 receptor agonists: a systematic review and nonlinear meta-regression (2026) · cites this paper as [11]
In the citing paper
“Some trials, such as STEP 411 and SURMOUNT-4,12 were designed to measure post-cessation outcomes and often included longer follow-up durations of up to 52 weeks, with data collected at multiple intervening time points.”
From Trajectory of weight regain after cessation of GLP-1 receptor agonists: a systematic review and nonlinear meta-regression (2026) · cites this paper as [11]
In the citing paper
“Randomised controlled trials such as STEP 4 and SURMOUNT-4 have demonstrated that significant weight regain occurs after cessation”
From Trajectory of weight regain after cessation of GLP-1 receptor agonists: a systematic review and nonlinear meta-regression (2026) · cites this paper as [11]
In the citing paper
“we identified only two large-scale RCTs that were designed to measure weight regain as a primary outcome: STEP 411 and SURMOUNT-4.12”
From Trajectory of weight regain after cessation of GLP-1 receptor agonists: a systematic review and nonlinear meta-regression (2026) · cites this paper as [11]
In the citing paper
“Looking beyond headline weight loss results, substantial response variability exists within patient populations, with the STEP and SURMOUNT trials reporting that 10% to 15% of individuals lose <5% on semaglutide or tirzepatide, respectively, and are thus classed as “nonresponders” (77, 79, 80, 94, 100).”
From GLP-1 and the Neurobiology of Eating Control: Recent Advances (2025) · cites this paper as [100]
In the citing paper
“with some studies demonstrating enhanced weight loss and reduced weight regain following cessation of GLP-1RA-based therapies (100, 125).”
From GLP-1 and the Neurobiology of Eating Control: Recent Advances (2025) · cites this paper as [100]
In the citing paper
“with reports that 50% to 65% of total weight loss is regained up to a year after semaglutide or tirzepatide cessation (100, 121, 122).”
From GLP-1 and the Neurobiology of Eating Control: Recent Advances (2025) · cites this paper as [100]
In the citing paper
“Therefore, a multimodal approach combining dietary interventions, structured physical activity, and pharmacological agents such as GLP-1 RA may offer a more effective and scalable strategy for preoperative weight management.59”
From Evaluation of safety of preoperative GLP-1 receptor agonists in patients undergoing elective surgery: a systematic review, meta-analysis and meta-regression (2025) · cites this paper as [59]
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Metadata
- Authors
- Rubino, D., Abrahamsson, N., Davies, M., Hesse, D., Greenway, F. L., Jensen, C., Lingvay, I., Mosenzon, O., Rosenstock, J., Rubio, M. A., Rudofsky, G., Tadayon, S., Wadden, T. A., Dicker, D., STEP 4 Investigators, Friberg, M., Sjödin, A., Dicker, D., Segal, G., Mosenzon, O., Sabbah, M., Sofer, Y., Vishlitzky, V., Meesters, E. W., Serlie, M., van Bon, A., Cardoso, H., Freitas, P., Carneiro de Melo, P., Monteiro, M., Monteiro, M., Rodrigues, D., Badat, A., Joshi, P., Latiff, G., Mitha, E. A., Snyman, H. H., van Nieuwenhuizen, E., González Albarrán, O., Caixas, A., de al Cuesta, C., Garcia Luna, P. P., Morales Portillo, C., Mezquita Raya, P., Rubio, M. A., Abrahamsson, N., Hoffstedt, J., von Wowern, F., Uddman, E., Bach-Kliegel, B., Beuschlein, F., Bilz, S., Golay, A., Rudofsky, G., Strey, C., Fadieienko, G., Kosei, N., Tatarchuk, T., Velychko, V., Zinych, O., Aronoff, S. L., Bays, H. E., Brockmyre, A. P., Call, R. S., Crump, C., Desouza, C. V., Espinosa, V., Free, A. L., Gandy, W. H., Geller, S. A., Gottschlich, G. M., Greenway, F. L., Han-Conrad, L., Harper, W., Herman, L., Hewitt, M., Hollander, P., Kaster, S. R., Manessis, A., Martin, F. A., McNeill, R. E., Murray, A. V., Norwood, P. C., Reed, J. C. H., Rosenstock, J., Rubino, D. M., Schear, M. J., & Warren, M. L.
- Affiliations
- Washington Center for Weight Management and Research (US)
- University of Leicester (GB)
- Novo Nordisk (Denmark) (DK)
- The University of Texas Southwestern Medical Center (US)
- Universidad Complutense de Madrid (ES)
- University of Pennsylvania (US)
- for the STEP 4 Investigators
- Corresponding author
- Rubino, Domenica
- ORCID
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2021-04-13
- Volume
- 325
- Issue
- 14
- Pages
- 1414
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- PMC
- PMC7988425
- OpenAlex
- W3138431202
- Cited by
- 1,444
- References
- 39
- Citations by year
- 2026: 393 · 2025: 376 · 2024: 271 · 2023: 187 · 2022: 141 · 2021: 69
- FWCI
- 97.49
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- JAMA (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, other-oa)
- Figshare (submittedVersion)
- Funders
- Eli Lilly and Company
- Pfizer
- AstraZeneca
- Sanofi
- University of Pennsylvania
- Regeneron Pharmaceuticals
- Hadassah Medical Organization
- Jazz Pharmaceuticals
- Intarcia Therapeutics
- MannKind Corporation
- Mylan
- Novo Nordisk
- Genentech
- National Institute of General Medical Sciences (U54GM104940)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Pharmacology and Obesity Treatment
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- semaglutide, weight loss maintenance, obesity, overweight, GLP-1 receptor agonists, treatment withdrawal, lifestyle intervention, body weight, waist circumference, blood pressure, physical function, SF-36, body mass index, weight-related comorbidities, dose escalation, sustained weight loss, weight regain prevention, antipsychotic-induced weight gain
- MeSH terms
- Semaglutide, Adult, Blood Pressure, Double-Blind Method, Glucagon-Like Peptides, Female, Humans, Injections, Subcutaneous, Male, Middle Aged, Obesity, Weight Loss, Anti-Obesity Agents, Overweight, Glucagon-Like Peptide 1, Waist Circumference
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-09-30, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-09-30 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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