The DOI matches its Crossref record; 34 of the 34 references it cites were found in a registry or an index; 8 of the 24 sources its claims cite were checked for support.
Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity: The STEP 3 Randomized Clinical Trial
Open accessAbstract
Importance: Weight loss improves cardiometabolic risk factors in people with overweight or obesity. Intensive lifestyle intervention and pharmacotherapy are the most effective noninvasive weight loss approaches. Objective: To compare the effects of once-weekly subcutaneous semaglutide, 2.4 mg vs placebo for weight management as an adjunct to intensive behavioral therapy with initial low-calorie diet in adults with overweight or obesity. Design, Setting, and Participants: Randomized, double-blind, parallel-group, 68-week, phase 3a study (STEP 3) conducted at 41 sites in the US from August 2018 to April 2020 in adults without diabetes (N = 611) and with either overweight (body mass index ≥27) plus at least 1 comorbidity or obesity (body mass index ≥30). Interventions: Participants were randomized (2:1) to semaglutide, 2.4 mg (n = 407) or placebo (n = 204), both combined with a low-calorie diet for the first 8 weeks and intensive behavioral therapy (ie, 30 counseling visits) during 68 weeks. Main Outcomes and Measures: The co-primary end points were percentage change in body weight and the loss of 5% or more of baseline weight by week 68. Confirmatory secondary end points included losses of at least 10% or 15% of baseline weight. Results: Of 611 randomized participants (495 women [81.0%], mean age 46 years [SD, 13], body weight 105.8 kg [SD, 22.9], and body mass index 38.0 [SD, 6.7]), 567 (92.8%) completed the trial, and 505 (82.7%) were receiving treatment at trial end. At week 68, the estimated mean body weight change from baseline was -16.0% for semaglutide vs -5.7% for placebo (difference, -10.3 percentage points [95% CI, -12.0 to -8.6]; P < .001). More participants treated with semaglutide vs placebo lost at least 5% of baseline body weight (86.6% vs 47.6%, respectively; P < .001). A higher proportion of participants in the semaglutide vs placebo group achieved weight losses of at least 10% or 15% (75.3% vs 27.0% and 55.8% vs 13.2%, respectively; P < .001). Gastrointestinal adverse events were more frequent with semaglutide (82.8%) vs placebo (63.2%). Treatment was discontinued owing to these events in 3.4% of semaglutide participants vs 0% of placebo participants. Conclusions and Relevance: Among adults with overweight or obesity, once-weekly subcutaneous semaglutide compared with placebo, used as an adjunct to intensive behavioral therapy and initial low-calorie diet, resulted in significantly greater weight loss during 68 weeks. Further research is needed to assess the durability of these findings. Trial Registration: ClinicalTrials.gov Identifier: NCT03611582.
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Claims the paper makes
56 Own result · 17 Own method · 4 Own interpretation · 3 Supported · 3 Partly supported · 3 Sources not found · 3 No full text of the sources · 2 Not checked yet · 1 Supported so far · accuracy not yet measured
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“The present findings suggest that the addition of semaglutide to intensive behavioral therapy may help patients achieve more than the average 5% to 10% reduction in body weight typically produced by behavioral interventions at 6 to 12 months.1,21”
§ Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity The STEP 3 Randomized Clinical Trial > Adverse Events
What the sources say
- Supportedcites [1] 1. Jensen MD, Ryan DH, Apovian CM, et al; American College of Cardiology/American Heart Association Task Force on Practice Guidelines; Obesity Society. 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Obesity Society. Circulation. 2014;129(25)(suppl 2):S102-S138. doi:10. 1161/01.cir.0000437739.71477.ee source
Section 3.4.2 (ES2a–ES2b) says comprehensive lifestyle interventions can produce average losses approximating 5%–10% of initial weight at 6 months, with comparable average losses at 1 year. The semaglutide comparison is framed as the citing authors’ interpretation of their present findings, not as a finding attributed to this guideline. (LLM, conf=0.91)
- Not checked — no full text of the sourcecites [21] 21. Webb VL, Wadden TA. Intensive lifestyle intervention for obesity: principles, practices, and results. Gastroenterology. 2017;152(7):1752-1764. doi:10.1053/j.gastro.2017.01.045 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.
- 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
“At week 68, levels of C-reactive protein and lipids had improved with semaglutide relative to placebo, with the exception of high-density lipoprotein cholesterol (Table 2 and eTable 1 in Supplement 1).”
§ Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity The STEP 3 Randomized Clinical Trial > 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.
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
“A higher proportion of participants in the semaglutide vs placebo group achieved weight losses of at least 10% or 15% (75.3% vs 27.0% and 55.8% vs 13.2%, respectively; P < .001).”
§ Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity The STEP 3 Randomized Clinical Trial > Abstract
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
“A higher proportion of participants in the semaglutide vs placebo group achieved weight losses of at least 10% or 15% (75.3% vs 27.0% and 55.8% vs 13.2%, respectively; P < .001).”
§ Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity The STEP 3 Randomized Clinical Trial > Abstract
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
“Semaglutide was associated with improvements vs placebo in BMI and diastolic blood pressure at week 68 (Table 2 and eTable 1 in Supplement 1).”
§ Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity The STEP 3 Randomized Clinical Trial > Supportive Secondary End Points
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.
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 adverse events were more frequent with semaglutide (82.8%) vs placebo (63.2%).”
§ Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity The STEP 3 Randomized Clinical Trial > Abstract
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.
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 proportion of participants reporting adverse events was similar in the semaglutide and placebo groups (95.8% and 96.1%, respectively).”
§ Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity The STEP 3 Randomized Clinical Trial > Adverse Events
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
“Reductions at week 68 in waist circumference and systolic blood pressure were significantly greater with semaglutide than with placebo (difference, -8.3 cm [95% CI, -10.1 to -6.6]; P < .001and -3.9 mm Hg [95% CI, -6.4 to -1.5]; P = .001,respectively)”
§ Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity The STEP 3 Randomized Clinical Trial > Confirmatory 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.
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
“Reductions at week 68 in waist circumference and systolic blood pressure were significantly greater with semaglutide than with placebo (difference, -8.3 cm [95% CI, -10.1 to -6.6]; P < .001and -3.9 mm Hg [95% CI, -6.4 to -1.5]; P = .001,respectively)”
§ Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity The STEP 3 Randomized Clinical Trial > Confirmatory 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.
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
“Semaglutide was associated with improvements vs placebo in BMI and diastolic blood pressure at week 68 (Table 2 and eTable 1 in Supplement 1).”
§ Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity The STEP 3 Randomized Clinical Trial > Supportive Secondary End Points
plaincorrelational- 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. 29
- It may state two separate claims as one. 18
- 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
“Weight loss can be increased by an additional 3 to 5 percentage points by including a low-calorie (1000-1200 kcal/d) portion-controlled diet composed of liquid shakes, meal bars, and prepared meals.2,3”
§ Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity The STEP 3 Randomized Clinical Trial > I
What the sources say
- Not checked — no full text of the sourcecites [2] 2. Heymsfield SB, van Mierlo CA, van der Knaap HC, Heo M, Frier HI. Weight management using a meal replacement strategy: meta and pooling analysis from six studies. Int J Obes Relat Metab Disord. 2003;27(5):537-549. doi:10.1038/sj.ijo. 0802258 source
- Partly supportedcites [3] 3. Wadden TA, Foster GD, Sarwer DB, et al. Dieting and the development of eating disorders in obese women: results of a randomized controlled trial. Am J Clin Nutr. 2004;80(3):560-568. doi:10.1093/ ajcn/80.3.560 sourceExperimental — accuracy not yet measured
The weight-results passage (page unavailable) reports 12.1% weight loss in the meal-replacement group versus 7.8% with a conventional-food diet at week 20—an additional 4.3 percentage points in obese women. The Meal replacement section (page unavailable) describes a 1000 kcal/day plan of liquid servings and an evening meal, not a 1000–1200 kcal/day plan including meal bars; the difference in weight loss was no longer significant at week 40. (LLM, conf=0.87)
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.
Every source the paper cites for this claim was checked and supports it.
In the paper
“Once-daily liraglutide, 3.0 mg, a glucagon-like peptide 1 receptor agonist approved for weight management, added approximately 3 to 5 percentage points of additional weight loss to intensive behavioral therapy compared with behavioral therapy alone.9,10”
§ Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity The STEP 3 Randomized Clinical Trial > I
What the sources say
- Supportedcites [9] 9. Wadden TA, Walsh OA, Berkowitz RI, et al. Intensive behavioral therapy for obesity combined with liraglutide 3.0 mg: a randomized controlled trial. Obesity (Silver Spring). 2019;27(1):75-86. doi: 10.1002/oby.22359 source
The Discussion reports that adding liraglutide 3.0 mg/day to intensive behavioral therapy increased mean one-year weight loss from 6.1% to 11.5% of initial weight. The difference is 5.4 percentage points, approximately the upper end of the claimed 3–5-point range. The Methods confirm once-daily administration. (LLM, conf=0.91)
- Supportedcites [10] 10. Wadden TA, Tronieri JS, Sugimoto D, et al. Liraglutide 3.0 mg and intensive behavioral therapy (IBT) for obesity in primary care: the SCALE IBT randomized controlled trial. Obesity (Silver Spring). 2020;28(3):529-536. doi:10.1002/oby.22726 source
The Results (Body weight) report 3.4 percentage points more weight loss at week 56 with liraglutide 3.0 mg plus IBT than with placebo plus IBT under the treatment-policy analysis. The corresponding difference under the if-all-adhered analysis was 4.6 percentage points. Both fall within the claimed approximate 3-to-5-point range. (LLM, conf=0.95)
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.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“A 20-week clinical study of participants with obe-sity found that treatment with once-weekly semaglutide, 2.4 mg, compared with placebo reduced self-reported hunger and food cravings and decreased energy intake during an ad libitum lunch by 35%.27”
§ Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity The STEP 3 Randomized Clinical Trial > Adverse Events
What the sources say
- Supportedcites [27] 27. 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 source
Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
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.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Larger-than-expected reductions in resting and nonresting energy expenditure that occur with weight loss (ie, metabolic adaptation), compensatory changes in other homeostatic regulators of body weight, and patients' behavioral fatigue in adhering to diet and activity recommendations may contribute to the 5% to 10% weight reduction plateau observed with behavioral therapy.[23][24][25]”
§ Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity The STEP 3 Randomized Clinical Trial > Adverse Events
What the sources say
- Not checked — no full text of the sourcecites [23] 23. 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
- Partly supportedcites [24] 24. Heckman BW, Mathew AR, Carpenter MJ. Treatment burden and treatment fatigue as barriers to health. Curr Opin Psychol. 2015;5:31-36. doi:10. 1016/j.copsyc.2015.03.004 sourceExperimental — accuracy not yet measured
The Chronic Disease and Health Behaviors section says treatment burden can reduce adherence to behavioral interventions, supporting the proposed role of behavioral fatigue. But Potential Applications says treatment fatigue had not been applied to obesity and does not link it to a 5%–10% weight-loss plateau. The paper does not address the sentence’s metabolic mechanisms, which appear alongside other citations. (LLM, conf=0.86)
- Not checked — no full text of the sourcecites [25] 25. Sumithran P, Prendergast LA, Delbridge E, et al. Long-term persistence of hormonal adaptations to weight loss. N Engl J Med. 2011;365(17):1597-1604. doi:10.1056/NEJMoa1105816 source
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.
Every source the paper cites for this claim was checked and supports it.
In the paper
“Preclinical studies suggest that weight loss with semaglutide results from its effects on glucagon-like peptide 1 receptors that mediate direct and indirect effects on the brain areas involved in regulation of appetite, including in the hypothalamus and hindbrain, ultimately leading to reduced energy intake.26”
§ Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity The STEP 3 Randomized Clinical Trial > Adverse Events
What the sources say
- Supportedcites [26] 26. 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
The Introduction says semaglutide interacts with neural GLP-1 receptors and directly and indirectly affects pathways involved in food intake. The Discussion concludes that it reduces body weight through direct effects in the hypothalamus and hindbrain and secondary effects elsewhere, with reduced food intake as the primary driver of weight loss. The supplied passages do not give page numbers. (LLM, conf=0.94)
hedgeddirect- 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.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Two estimands were used to address different scientific questions, as described elsewhere.17,18”
§ Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity The STEP 3 Randomized Clinical Trial > Statistical Analysis
What the sources say
- Not matchedcites [17] 17. Food and Drug Administration. E9(R1) statistical principles for clinical trials: addendum: estimands and sensitivity analysis in clinical trials. Accessed October 22, 2020. https://www.fda.gov/media/ 108698/download
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Supportedcites [18] 18. Wharton S, Astrup A, Endahl L, et al. Estimating and reporting treatment effects in clinical trials for weight management: using estimands to interpret effects of intercurrent events and missing data. Int J Obes (Lond). Published online January 18, 2021. doi: 10.1038/s41366-020-00733-x source
The section on estimating treatment effects says that different scientific questions can be addressed by multiple estimands in one trial. It distinguishes the treatment policy estimand, which estimates a population-level effect, from the hypothetical or trial product estimand, which estimates a pharmacological effect assuming no intercurrent events. Page numbers were not available in our copy. (LLM, conf=0.90)
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.
- Not matched
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
“At week 68, the estimated change in pulse from baseline was 3.1/min for semaglutide vs 2.1/min for placebo (trial product estimand difference, 1.0/min [95% CI, -0.7 to 2.6]) (eTable 2 in Supplement 1).”
§ Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity The STEP 3 Randomized Clinical Trial > Adverse Events
hedged- 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.
- The authors state this as an assumption: All randomized participants remained receiving randomized treatment for the duration of the trial and did not receive rescue intervention.
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 baseline to week 68, SF-36 physical component summary score improved similarly in both groups, whereas the mental component summary score favored semaglutide (Table 2; eTable 1 and eFigure 7 in Supplement 1).”
§ Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity The STEP 3 Randomized Clinical Trial > Supportive Secondary End Points
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
“At any given time during the study, the proportion of participants who experienced vomiting was less than 5% in both treatment groups.”
§ Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity The STEP 3 Randomized Clinical Trial > Adverse Events
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
“The proportion of participants experiencing nausea with semaglutide peaked at approximately 25% at week 20 and declined thereafter, remaining at approximately 15% for the duration of the study.”
§ Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity The STEP 3 Randomized Clinical Trial > Adverse Events
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
“No deaths were reported during the study.”
§ Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity The STEP 3 Randomized Clinical Trial > Adverse Events
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
“Malignant neoplasms were reported in 3 semaglutide-treated participants (0.7%; basal cell carcinoma, breast cancer, and papillary thyroid cancer) and 1 placebo-treated participant (0.5%; invasive lobular breast carcinoma).”
§ Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity The STEP 3 Randomized Clinical Trial > Adverse Events
plainn = 3- 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
“There were no cases of acute pancreatitis, medullary thyroid carcinoma, or pancreatic cancer in either group.”
§ Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity The STEP 3 Randomized Clinical Trial > Adverse Events
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
“At the follow-up visit (week 75) after the offtreatment period, mean pulse had neared the baseline level.”
§ Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity The STEP 3 Randomized Clinical Trial > Adverse Events
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
“From baseline to week 68, SF-36 physical component summary score improved similarly in both groups, whereas the mental component summary score favored semaglutide (Table 2; eTable 1 and eFigure 7 in Supplement 1).”
§ Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity The STEP 3 Randomized Clinical Trial > Supportive Secondary End Points
plaincorrelational- 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
“More participants discontinued treatment due to adverse events in the semaglutide group (5.9%) compared with placebo (2.9%), mainly because of gastrointestinal events (Table 3).”
§ Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity The STEP 3 Randomized Clinical Trial > Adverse Events
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
“SF-36 physical functioning score d | 2.4 | 1.6 | 0.8 (-0.2 to 1.9) | | .12”
§ Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity The STEP 3 Randomized Clinical Trial > Additional Contributions:
plainn = 407- 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
“Gastrointestinal disorders | 14 (3.4) | 20 | 3.8 | 0 | |”
§ Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity The STEP 3 Randomized Clinical Trial > Additional Contributions:
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.
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
“Mental component summary score | -0.8 | -2.9 | 2.1 (0.5 to 3.6) | | .011”
§ Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity The STEP 3 Randomized Clinical Trial > Additional Contributions:
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
“A sample size of 600 participants was calculated to provide power of 86% for the 7 end points in the hierarchic testing procedure, with greater than 99% power for the co-primary end points”
§ Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity The STEP 3 Randomized Clinical Trial > Statistical Analysis
plainn = 600- 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.
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
“STEP 3 was a 68-week, randomized, double-blind, placebocontrolled, multicenter study conducted at 41 sites in the US from August 2018 to April 2020.”
§ Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity The STEP 3 Randomized Clinical Trial > Study 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.
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
“Observed benefits of weight loss might have been larger if participants had been selected because of having elevated risk factors (eg, hypertension, hyperlipidemia), which they were not in the present study.”
§ Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity The STEP 3 Randomized Clinical Trial > Adverse Events
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: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
In the paper
“Larger weight losses (eg, ≥10%) are desired because they produce greater improvements in several obesityrelated cardiometabolic risk factors and diseases, including type 2 diabetes, hypertension, and sleep apnea.[4][5][6][7][8]”
§ Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity The STEP 3 Randomized Clinical Trial > I
What the sources say
- Not matchedcites [4][5][6][7][8]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
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.
- 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 were randomized 2:1 with a blocking schema (block size of 9) via an interactive web-response system to onceweekly subcutaneous semaglutide, 2.4 mg, or visually identical placebo for 68 weeks”
§ Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity The STEP 3 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.
None of the sources cited for this claim have been checked yet.
In the paper
“Subcutaneous semaglutide is a long-acting glucagon-like peptide 1 receptor agonist approved for the treatment of type 2 diabetes at once-weekly doses of up to 1.0 mg, 11 which reduces body weight by approximately 6% by 1 year in these patients.12,13”
§ Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity The STEP 3 Randomized Clinical Trial > I
What the sources say
- Not matchedcites [11] 11. Food and Drug Administration. Ozempic (semaglutide) injection, for subcutaneous use [prescribing information]. Accessed September 25, 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.
- Not checked — no full text of the sourcecites [12] 12. Ahmann AJ, Capehorn M, Charpentier G, et al. Efficacy and safety of once-weekly semaglutide versus exenatide ER in subjects with type 2 diabetes (SUSTAIN 3): a 56-week, open-label, randomized clinical trial. Diabetes Care. 2018;41(2): 258-266. doi:10.2337/dc17-0417 source
- Not checked — no full text of the sourcecites [13] 13. Ahrén B, Masmiquel L, Kumar H, et al. Efficacy and safety of once-weekly semaglutide versus once-daily sitagliptin as an add-on to metformin, thiazolidinediones, or both, in patients with type 2 diabetes (SUSTAIN 2): a 56-week, double-blind, phase 3a, randomised trial. Lancet Diabetes Endocrinol. 2017;5(5):341-354. doi:10.1016/S2213- 8587(17)30092-X source
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. 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
“The larger proportions of participants treated with semaglutide compared with placebo who achieved categorical weight losses of at least 10%, 15%, or 20% translated into greater improvements in waist circumference, blood pressure, glycated hemoglobin level, C-reactive protein level, and several lipid parameters.”
§ Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity The STEP 3 Randomized Clinical Trial > Adverse Events
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
“Efficacy end points were analyzed with the full analysis set (ie, all participants randomly assigned to a treatment group regardless of whether they initiated treatment), and adverse event end points were analyzed with the safety analysis set (ie, all randomized participants exposed to at least 1 dose of randomized treatment).”
§ Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity The STEP 3 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. 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
“The superiority of subcutaneous semaglutide to placebo for the primary and secondary confirmatory end points was assessed in hierarchic order, with superiority at a significance level of 5% required before testing of subsequent end points in the hierarchy.”
§ Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity The STEP 3 Randomized Clinical Trial > Statistical Analysis
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.
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
“Overall, 567 participants (92.8%) completed the trial, and 505 (82.7%) completed the trial in the on-treatment period (Figure 1).”
§ Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity The STEP 3 Randomized Clinical Trial > Study Participants
plainn = 567- 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
“In the semaglutide group, 12 were lost to follow-up by week 38, and in the placebo group, 5 were lost to follow-up by week 25.”
§ Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity The STEP 3 Randomized Clinical Trial > Additional Contributions:
plainn = 12- 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
“The study was conducted according to consensus ethical principles derived from guidelines, including the Declaration of Helsinki, the International Conference on Harmonization Good Clinical Practice Guideline, and applicable local laws and regulations.”
§ Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity The STEP 3 Randomized Clinical Trial > Study 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.
In the paper
“Missing data were imputed with a multiple imputation approach, similar to that described by McEvoy.19 Missing body weight measurements were imputed by sampling from available measurements at week 68 from participants receiving randomized treatment in the relevant randomized treatment group.Missing values were multiply imputed (× 1000).”
§ Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity The STEP 3 Randomized Clinical Trial > Statistical Analysis
What the sources say
- Not checked — no full text of the sourcecites [19] 19. McEvoy BW. Missing data in clinical trials for weight management. J Biopharm Stat. 2016;26(1): 30-36. doi:10.1080/10543406.2015.1094814 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.
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 participants provided written informed consent.”
§ Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity The STEP 3 Randomized Clinical Trial > Study 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.
In the paper
“Participants in STEP 1 lost 14.9% of baseline weight with semaglutide at 68 weeks, compared with 2.4% for placebo plus the same lifestyle intervention.31”
§ Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity The STEP 3 Randomized Clinical Trial > Adverse Events
What the sources say
- Not checked yetcites [31] 31. Wilding JPH, Batterham RL, Calanna S, et al; the STEP 1 Study Group. Once-weekly semaglutide in adults with overweight or obesity. N Engl J Med. Published February 10, 2021. doi:10.1056/ NEJMoa2032183
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
“The primary hierarchic statistical analyses were based on the treatment policy es-timand (similar to an intention-to-treat analysis), which quantified the average treatment effect among all randomized participants, regardless of adherence to treatment or initiation of rescue interventions (ie, antiobesity medications or bariatric surgery).”
§ Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity The STEP 3 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.
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, this was a relatively brief trial, which did not address whether semaglutide-treated participants would sustain their 16% weight reduction if they continued to receive the medication past 68 weeks.”
§ Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity The STEP 3 Randomized Clinical Trial > Limitations
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
“The proportion of participants permanently discontinuing trial product was similar between treatment groups (semaglutide, 16.7%; placebo, 18.6%) (eFigure 2 in Supplement 1).”
§ Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity The STEP 3 Randomized Clinical Trial > Study Participants
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
“First, it could not identify the separate contributions to weight loss of intensive behavioral therapy and the initial low-calorie diet in the placebo group or, as previously indicated, determine the relative benefit of combining either of these enhanced interventions with semaglutide.”
§ Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity The STEP 3 Randomized Clinical Trial > Limitations
hedged- 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
“The protocol and amendments (available in Supplement 2) were approved by institutional review boards or independent ethics committees at each study site.”
§ Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity The STEP 3 Randomized Clinical Trial > Study 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.
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
“A total of 5.6% of participants were lost to follow-up.”
§ Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity The STEP 3 Randomized Clinical Trial > Additional Contributions:
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
“Selected adverse events (eg, cardiovascular events, acute pancreatitis) and deaths were reviewed by an independent external event adjudication committee.”
§ Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity The STEP 3 Randomized Clinical Trial > End Points
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.
The authors state this as an assumption.
All randomized participants remained receiving randomized treatment for the duration of the trial and did not receive rescue intervention.
“The trial product estimand quantified the average treatment effect in all randomized participants, assuming they remained receiving randomized treatment for the duration of the trial (and without rescue intervention).”
The paper relies on this without support.
The STEP 1 and STEP 3 trial populations and lifestyle interventions are sufficiently comparable to allow an indirect comparison of weight loss outcomes.
“These findings suggest that the inclusion of intensive behavioral therapy plus an 8-week low-calorie diet ultimately may not contribute significant additional weight loss beyond that achieved by semaglutide and less-intensive lifestyle intervention.”
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
“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 [754]
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 SURMOUNT‐3 trial, individuals who received tirzepatide after a comprehensive 12‐week lifestyle intervention achieved a mean 25% weight reduction, compared to 4.8% in the placebo group [178]”
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 [178]
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
“whereas in the SURMOUNT 3 trial, tirzepatide 10 or 15 mg/wk started after 12 weeks of intensive lifestyle intervention produced a 25% reduction from baseline (versus 4.8% with intensive lifestyle intervention alone) [178].”
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 [178]
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
“whereas in the SURMOUNT 3 trial, tirzepatide 10 or 15 mg/week started after 12 weeks of intensive lifestyle intervention produced a 25% reduction from baseline (vs. 4.8% with intensive lifestyle intervention alone) [178].”
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 [178]
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 clinical trials of liraglutide 3 mg, the incidence of cholelithiasis was greater than placebo.741,754”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [754]
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
“As the new obesity pharmacotherapies will lead up to 15–25% mean WL, intensive lifestyle interventions may provide small additional WL benefit to these treatments [11, 106].”
From What is the pipeline for future medications for obesity? (2025) · cites this paper as [106]
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 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 [14]
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 [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
“Gallbladder-related disorders (primarily cholelithiasis) were reported in 2.6% vs 1.2% of participants on semaglutide vs placebo in STEP 1, 0.2% vs 0.7% of participants in STEP 2, and 4.9% vs 1.5% in STEP 3.”
From Semaglutide for the treatment of obesity (2023) · cites this paper as [36]
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 [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
“Furthermore, four studies (n = 3087) 16,17,19,20 revealed that semaglutide led to a greater percentage of trial discontinuations due to GI AEs relative to placebo (RR 5.36, [95% CI 2.49, 11.55]; P < 0.0001 [Figure S16]).”
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 [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
“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 [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
“Four studies (n = 3087) 16,17,19,20 reported a modification in levels of CRP, an indicator of inflammation. Evaluation of the combined analysis showed that semaglutide caused a significant reduction in CRP compared to placebo (MD: 38.92% [95% CI 43.69, 34.16]; P < 0.00001)”
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 [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
“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 [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
“Several RCTs have demonstrated a significantly higher prevalence of gallbladder disorders among patients treated with GLP-1 RAs compared to placebo [29-32], as initially evidenced by the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) trial, which reported acute gallstone disease rates of 3.1% in the liraglutide group versus 1.9% in the placebo”
From Exploring the Side Effects of GLP-1 Receptor Agonist: To Ensure Its Optimal Positioning (2025) · cites this paper as [31]
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 incidence of thyroid cancer in semaglutide-treated patients was less than 1%, suggesting no significant risk.”
From Assessment of Thyroid Carcinogenic Risk and Safety Profile of GLP1-RA Semaglutide (Ozempic) Therapy for Diabetes Mellitus and Obesity: A Systematic Literature Review (2024) · cites this paper as [30]
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
“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 [74]
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 [37]
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 [37]
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
“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 [37]
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 [37]
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
“STEP 3 comprised a more intensive behavioral support program, with a hypoenergetic diet (1,200-1,800 kcal/day), increased physical activity, and 30 intensive behavioral therapy visits across the 68 week duration of the study, and achieved a somewhat greater weight loss of 16%.”
From The societal implications of using glucagon-like peptide-1 receptor agonists for the treatment of obesity (2025) · 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
“As pharmacotherapy produces greater weight-loss maintenance than lifestyle alone (eg, STEP 3 Trial: difference, 10.3%; 95% CI, 8.6%-12.0%),12,99”
From Obesity Management in Adults: A Review (2023) · cites this paper as [99]
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
“Third, many RCTs included relatively few people from racial and ethnic minority groups and relatively small proportions of men.81,99”
From Obesity Management in Adults: A Review (2023) · cites this paper as [99]
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 [33]
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
“Across all structured interventions [23, 26, 28, 29], the lack of diet‐only comparator arms and the inconsistent measurement of protein intake and micronutrient deficiency limited conclusions about the independent contribution of the nutritional component and its role in mitigating nutritional risks.”
From Nutrition Strategies for Next‐Generation Incretin Therapies: A Systematic Scoping Review of the Current Evidence (2026) · cites this paper as [28]
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
“These constraints limit statistical power and preclude robust evaluation of long‐term outcomes, including sustained weight maintenance, micronutrient status, and preservation of lean tissue mass [5, 18, 28].”
From Nutrition Strategies for Next‐Generation Incretin Therapies: A Systematic Scoping Review of the Current Evidence (2026) · cites this paper as [28]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“as it is well-known that weight loss has an anti-inflammatory effect [30–32]”
From Impact of semaglutide on high-sensitivity C-reactive protein: exploratory patient-level analyses of SUSTAIN and PIONEER randomized clinical trials (2022) · cites this paper as [32]
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 [6]
The cited source says what the claim attributes to it.
In the citing paper
“These reductions in HbA1c levels were accompanied by notable weight loss, with changes from −1.9 kg in the study by Ahrén et al. [23] with Sitagliptin as the comparison group, to an impressive −16.0% of body weight loss reported in Wadden et al. [30] with a 2.4 mg weekly dose of subcutaneous semaglutide”
The cited source says what the claim attributes to it.
In the citing paper
“In the STEP 3 trial of semaglutide combined with intensive lifestyle intervention (30 counseling visits across 68 weeks, including nutrition, physical activity, and other behavioral strategies, plus 8 initial weeks of meal replacements with liquid shakes, meal bars, or portion‐controlled meals), individuals experienced a 16% reduction from baseline in body weight (vs. 5.7% with intensive lifestyle”
The cited source says what the claim attributes to it.
In the citing paper
“In these clinical trials, mean weight loss at 68 weeks was 14.9% (placebo, 2.4%; difference, 12.4%; 95% CI, 11.5%-13.4%) and 16.0% (placebo, 5.7%; difference, 10.3%; 95% CI, 8.6%-12.0%), respectively.81,99”
From Obesity Management in Adults: A Review (2023) · cites this paper as [99]
The cited source says what the claim attributes to it.
In the citing paper
“Seven of the 10 RCTs were judged to have a low risk of bias based on the RoB 2 tool [5, 6, 13, 14, 26, 28, 29].”
From Nutrition Strategies for Next‐Generation Incretin Therapies: A Systematic Scoping Review of the Current Evidence (2026) · cites this paper as [28]
The cited source says what the claim attributes to it.
In the citing paper
“However, no quantitative assessments of dietary intake or biochemical measures of nutrient adequacy were reported.”
From Nutrition Strategies for Next‐Generation Incretin Therapies: A Systematic Scoping Review of the Current Evidence (2026) · cites this paper as [28]
The cited source says what the claim attributes to it.
In the citing paper
“weight loss was significantly greater with semaglutide compared with placebo (16.0% compared with 5.7%; p < 0.001)”
From Nutrition Strategies for Next‐Generation Incretin Therapies: A Systematic Scoping Review of the Current Evidence (2026) · cites this paper as [28]
In the citing paper
“In STEP 1 and 3, participants were randomized 2:1 to escalating doses of semaglutide up to 2.4 mg/week or placebo for 68 weeks as an adjunct to either lifestyle intervention”
In the citing paper
“All three trials were conducted according to the International Conference on Harmonisation Good Clinical Practice Guideline and the Declaration of Helsinki; all participants provided written informed consent (14,18,19).”
In the citing paper
“Semaglutide has been shown to lower body weight by up to 16% when used in conjunction with lifestyle recommendations [10, 11, 12, 13].”
From Semaglutide for cardiovascular event reduction in people with overweight or obesity: SELECT study baseline characteristics (2023) · cites this paper as [12]
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 [12]
In the citing paper
“In the phase III Semaglutide Treatment Effect in People with obesity (STEP) 1‐4 studies, weekly semaglutide 2.4 mg demonstrated substantial, clinically meaningful weight losses and improvements in cardiometabolic parameters and patient‐reported outcomes.”
In the citing paper
“In particular, at a dosage of 2.4 mg per week, it has been shown to induce an average weight loss between 9.6% and 17.4%, as well as a reduction in waist circumference and arterial hypertension and an improvement of lipid profile [34,35,36,37,39].”
From GLP-1 Receptor Agonists in Non-Alcoholic Fatty Liver Disease: Current Evidence and Future Perspectives (2023) · cites this paper as [36]
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 [18]
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 [16]
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 [16]
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 [16]
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 [16]
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 [16]
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 [94]
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 [58]
In the citing paper
“The proportion of patients with premature discontinuation because of adverse events was 5.9–7.0% in the semaglutide groups and 2.9–3.5% in the placebo groups.”
From Semaglutide for the treatment of obesity (2023) · cites this paper as [36]
In the citing paper
“Semaglutide-treated participants were more likely than placebo to lose ≥5%, ≥10%, ≥15%, and ≥20% of initial weight, with 35.7% and 3.7% of participants, respectively, meeting the last criterion (Figure 3).”
From Semaglutide for the treatment of obesity (2023) · cites this paper as [36]
In the citing paper
“Most gastrointestinal events were mild-to-moderate in severity, transient, and occurred during the first 20 weeks of treatment during dose escalation.”
From Semaglutide for the treatment of obesity (2023) · cites this paper as [36]
In the citing paper
“Participants in the semaglutide group, relative to placebo, had greater reductions in waist circumference, systolic and diastolic blood pressure, c-reactive protein, hemoglobin A1c, and lipids (with the exception of HDL; Table 1).”
From Semaglutide for the treatment of obesity (2023) · cites this paper as [36]
In the citing paper
“Participants who received semaglutide with intensive behavioral therapy lost 16.0% of initial weight at week 68, compared with 5.7% for placebo (estimated treatment difference = −10.3 percentage points; 95% CI=−12.0% to −8.6%, p<0.001; Figure 2).”
From Semaglutide for the treatment of obesity (2023) · cites this paper as [36]
In the citing paper
“Groups did not differ significantly in physical function.”
From Semaglutide for the treatment of obesity (2023) · cites this paper as [36]
In the citing paper
“In STEP trials 1–3, the percent of participants in the semaglutide 2.4 mg vs placebo groups who experienced nausea was 33.7–58.2% versus 9.2–22.1%; diarrhea was 21.3–36.1% vs 11.9–22.1%; vomiting was 21.8–27.3% vs 2.7–10.8%; and constipation was 17.4–36.9% vs 5.5–24.5%.”
From Semaglutide for the treatment of obesity (2023) · cites this paper as [36]
In the citing paper
“As with other GLP-1 receptor agonists, semaglutide is associated with increases in heart rate of 1 to 4 beats per minute.(34–36, 38)”
From Semaglutide for the treatment of obesity (2023) · cites this paper as [36]
In the citing paper
“However, this combined intervention produced a 16% loss at week 68, only 1 percentage point greater than that observed in STEP 1.”
From Semaglutide for the treatment of obesity (2023) · cites this paper as [36]
In the citing paper
“In STEP 1 and STEP 3, patients on semaglutide lost 14.8–16.0% BW compared to 2.4–5.7% in the placebo group at 68 weeks26,27.”
From Incretin-based therapies for the treatment of obesity-related diseases (2024) · cites this paper as [26]
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 [111]
In the citing paper
“In the SURMOUNT-3 trial, individuals who received tirzepatide after a comprehensive 12-week lifestyle intervention achieved a mean 25% weight reduction, compared to 4.8% in the placebo group [178]”
In the citing paper
“Compared to the STEP 1 trial, individuals in the STEP 3 placebo group lost more weight with the addition of IBT; however, mean weight reduction in the semaglutide group was only 1% greater than that observed in STEP 1.”
From New Frontiers in Obesity Treatment: GLP-1 and Nascent Nutrient-Stimulated Hormone-Based Therapeutics (2023) · cites this paper as [35]
In the citing paper
“Estimated mean weight change from baseline was 16% with semaglutide versus 5.7% with placebo (mean difference of 10.3%) (35).”
From New Frontiers in Obesity Treatment: GLP-1 and Nascent Nutrient-Stimulated Hormone-Based Therapeutics (2023) · cites this paper as [35]
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 [93]
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 [32]
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 [94]
In the citing paper
“However, the STEP3 trial did include an 8-week low-calorie diet prior to semaglutide initiation (94), which did not result in notably greater weight loss than the STEP1 trial which did not include such a lead-in (79)”
From GLP-1 and the Neurobiology of Eating Control: Recent Advances (2025) · cites this paper as [94]
In the citing paper
“The most successful obesity therapeutics – glucagon-like peptide-1 receptor (GLP1R) agonists – cause aversive responses such as nausea and vomiting1,2, effects which may contribute to their efficacy.”
From Dissociable hindbrain GLP1R circuits for satiety and aversion (2024) · cites this paper as [1]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity The STEP 3 Randomized Clinical Trial > Additional Contributions:
“A total of 5.6% of participants were lost to follow-up.”
§ Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity The STEP 3 Randomized Clinical Trial > Co-Primary End Points
“18 Lost to follow-up c 4 Withdrew consent 4 Other 2 Adverse event 3 Withdrew from trial 12 Discontinued treatment prematurely b (and withdrew from trial) 7 Lost to follow-up c”
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GLP-1 physiology informs the pharmacotherapy of obesity
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“The STEP 3 trial evaluated the effect of semaglutide on weight loss in individuals assigned to an initial low-calorie diet for 8 weeks and 30 sessions of intensive behavioral therapy plus 200 min of physical activity, over 68 weeks [86].”
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Self-citationPharmacotherapy of obesity: an update on the available medications and drugs under investigation
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Self-citationOnce-Weekly Semaglutide in Persons with Obesity and Knee Osteoarthritis
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Self-citationSignaling pathways in obesity: mechanisms and therapeutic interventions
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International Consensus Statement on Obstructive Sleep Apnea
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AGA Clinical Practice Guideline on Pharmacological Interventions for Adults With Obesity
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What is the pipeline for future medications for obesity?
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“As the new obesity pharmacotherapies will lead up to 15 – 25% mean WL, intensive lifestyle interventions may provide small additional WL bene fi t to these treatments [11, 106].”
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“2021 Wadden [36] 611 non-diabetic obese/overweight patients Prospective double-blind Semaglutide vs placebo Yes Semaglutide (2.”
BackgroundEmerging role of GLP-1 agonists in obesity: A comprehensive review of randomised controlled trials
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RetractedClinical management and treatment of obesity in China
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Self-citationMedications for Obesity: A Review
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GLP−1 receptor agonists for the treatment of obesity: Role as a promising approach
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“STEP 8 and STEP 3 showed similar results (101, 102).”
ResultWegovy (Semaglutide): A New Weight Loss Drug for Chronic Weight Management
Singh, G., Krauthamer, M., & Bjalme-Evans, M. (2021) · Journal of Investigative Medicine · doi:10.1136/jim-2021-001952 · Cited by 318
Weight Loss Outcomes Associated With Semaglutide Treatment for Patients With Overweight or Obesity
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Semaglutide for the treatment of obesity
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A review of current guidelines for the treatment of obesity
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“4 mg demonstrated substantial, clinically meaningful weight losses and improvements in cardiometabolic parameters and patient-reported outcomes.(8-11) Gastrointestinal (GI) adverse events (AEs), most commonly mild-tomoderate nausea, are a dose-dependent class effect of GLP-1RAs.”
BackgroundMethodSelf-citationObesity in South and Southeast Asia—A new consensus on care and management
Tham, K. W., Abdul Ghani, R., Cua, S. C., Deerochanawong, C., Fojas, M., Hocking, S., Lee, J., Nam, T. Q., Pathan, F., Saboo, B., et al. (2023) · Obesity Reviews · doi:10.1111/obr.13520 · Cited by 187
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Diets and drugs for weight loss and health in obesity – An update
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“…trial in patients with obesity found that semaglutide treatment (2.8 mg weekly) led to a weight loss of 14.9% compared with 2.4% with placebo [101], while another study with similar design and follow-up period found a weight-loss of 16% with semaglutide and 5.7% with placebo [102].”
ResultInfluentialThe Related Metabolic Diseases and Treatments of Obesity
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Dissociable hindbrain GLP1R circuits for satiety and aversion
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The Emerging Role of Glucagon-like Peptide-1 Receptor Agonists for the Management of NAFLD
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New Frontiers in Obesity Treatment: GLP-1 and Nascent Nutrient-Stimulated Hormone-Based Therapeutics
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Central nervous system regulation of organismal energy and glucose homeostasis
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New insights into the treatment of obesity
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“Nevertheless, compared to placebo, semaglutide demonstrated a higher proportion of subjects discontinuing treatment due to side effects (especially gastrointestinal) (101, 111).”
ResultInfluentialNext generation GLP-1/GIP/glucagon triple agonists normalize body weight in obese mice
Knerr, P. J., Mowery, S. A., Douros, J. D., Premdjee, B., Hjøllund, K. R., He, Y., Kruse Hansen, A. M., Olsen, A. K., Perez-Tilve, D., DiMarchi, R. D., et al. (2022) · Molecular Metabolism · doi:10.1016/j.molmet.2022.101533 · Cited by 152
Recent Advances in Incretin-Based Pharmacotherapies for the Treatment of Obesity and Diabetes
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“The STEP clinical program examining semaglutide efficacy in treating obesity showed clear female predominance, with STEP 1 including 74.1% of females [134], STEP 3 including 81% of females [135], STEP 4 including 79% [136], and STEP 5 including 77.6% of females [137].”
InfluentialKloock, S., Ziegler, C. G., & Dischinger, U. (2023) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2023.108549 · Cited by 173
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“…limited direct evidence has evaluated use of GLP-1s with or without RDN-provided MNT, the SCALE [13], STEP 1 [14], SURMOUNT [15], and STEP 3 [169] trials each demonstrated substantial weight reduction by combining GLP-1s with regular counseling sessions by RDNs or other qualified healthcare…”
InfluentialAlkhezi, O. S., Alahmed, A. A., Alfayez, O. M., Alzuman, O. A., Almutairi, A. R., & Almohammed, O. A. (2023) · Obesity Reviews · doi:10.1111/obr.13543 · Cited by 139
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Efficacy and Safety of Tirzepatide in Type 2 Diabetes and Obesity Management
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“4 mg once weekly, showed weight-loss effects comparable with bariatric surgery in three RCTs in patients with obesity [20-22].”
BackgroundMu, Y., Bao, X., Eliaschewitz, F. G., Hansen, M., Kim, B. T., Koroleva, A., Ronald, C. W., Yang, T., Zu, N., & Liu, M. R. (2024) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(23)00388-1 · Cited by 141
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Self-citationMozaffarian, D., Agarwal, M., Aggarwal, M., Alexander, L., Apovian, C. M., Bindlish, S., Bonnet, J., Butsch, W. S., Christensen, S., Gianos, E., et al. (2025) · Obesity · doi:10.1002/oby.24336 · Cited by 143
“…limited direct evidence has evaluated use of GLP-1s with or without RDN-provided MNT, the SCALE [13], STEP 1 [14], SURMOUNT [15], and STEP 3 [178] trials each demonstrated substantial weight reduction by combining GLP-1s with regular counseling sessions by RDNs or other qualified healthcare…”
Novel Noninvasive Approaches to the Treatment of Obesity: From Pharmacotherapy to Gene Therapy
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“The magnitude of the observed changes was generally similar to that in STEP 1, suggesting intensive lifestyle intervention may not be required to achieve beneficial effects with semaglutide.(19) With respect to other GLP-1RAs, s.”
ResultSelf-citationHu, W., Song, R., Cheng, R., Liu, C., Guo, R., Tang, W., Zhang, J., Zhao, Q., Li, X., & Liu, J. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.927859 · Cited by 127
“, 2021 (52) NCT03611582 75 Semaglutide Placebo 1/407 0/204 46.”
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Yang, Z., Lv, Y., Yu, M., Mei, M., Xiang, L., Zhao, S., & Li, R. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.925377 · Cited by 120
“In 2021, STEP 3 (Wadden et al., 2021) and STEP 4 (Rubino et al., 2021) reported the incidence of malignancy in overweight or obese adults as 0.7% (3/ 407) and 1.1% (6/535) in the semaglutide group and 0.5% (1/204) and 0.4% (1/268) in the control group, respectively.”
BackgroundInfluentialGlucagon-Like Peptide 1 Receptor Agonists and Mental Health: A Systematic Review and Meta-Analysis
Pierret, A. C. S., Mizuno, Y., Saunders, P., Lim, E., De Giorgi, R., Howes, O. D., McCutcheon, R. A., McGowan, B., Sen Gupta, P., Smith, D., et al. (2025) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2025.0679 · Cited by 116
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Sibony, R. W., Segev, O., Dor, S., & Raz, I. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242417147 · Cited by 151
“The recently published STEP 1 (Semaglutide Treatment Effect in People with Obesity) [53], STEP 2 [54], STEP 3 [55], and STEP 4 [56], trials demonstrate the tremendous impact of weekly GLP-1RA treatment with semaglutide on weight loss and cardiovascular risk factors.”
BackgroundNew horizons. A new paradigm for treating to target with second-generation obesity medications
Garvey, W. T. (2022) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgab848 · Cited by 110
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Self-citationThe Low-Carbohydrate Diet: Short-Term Metabolic Efficacy Versus Longer-Term Limitations
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Self-citationTargeting the incretin system in obesity and type 2 diabetes mellitus
Ansari, S., Khoo, B. C. E., & Tan, T. (2024) · Nature Reviews Endocrinology · doi:10.1038/s41574-024-00979-9 · Cited by 110
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Self-citationApproach to Obesity Treatment in Primary Care: A Review
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Metadata
- Authors
- Wadden, T. A., Bailey, T. S., Billings, L. K., Davies, M., Frias, J. P., Koroleva, A., Lingvay, I., O’Neil, P. M., Rubino, D. M., Skovgaard, D., Wallenstein, S. O. R., Garvey, W. T., & STEP 3 Investigators
- Affiliations
- University of Pennsylvania (US)
- AMCR Institute (US)
- Endeavor Health (US)
- University of Leicester (GB)
- National Research Institute, Los Angeles, California
- Novo Nordisk (Denmark) (DK)
- The University of Texas Southwestern Medical Center (US)
- Weight Management Center, Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston
- Washington Center for Weight Management and Research (US)
- University of Alabama at Birmingham (US)
- Corresponding author
- Wadden, Thomas A.
- ORCID
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2021-04-13
- Volume
- 325
- Issue
- 14
- Pages
- 1403
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- PMC
- PMC7905697
- OpenAlex
- W3129305070
- Cited by
- 1,114
- References
- 33
- Citations by year
- 2026: 237 · 2025: 287 · 2024: 222 · 2023: 147 · 2022: 132 · 2021: 85
- FWCI
- 85.54
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- JAMA (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Figshare (submittedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK079626)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Pharmacology and Obesity Treatment
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Surgery › Bariatric Surgery and Outcomes
- Keywords
- semaglutide, obesity, overweight, weight loss, hypocaloric diet, GLP-1 receptor agonists, pharmacotherapy, adjunctive therapy, comorbid obesity, cardiometabolic risk factors, weight regain after weight loss
- MeSH terms
- Semaglutide, Adult, Combined Modality Therapy, Diet, Reducing, Double-Blind Method, Glucagon-Like Peptides, Female, Humans, Injections, Subcutaneous, Male, Middle Aged, Obesity, Weight Loss, Cognitive Behavioral Therapy, Anti-Obesity Agents, Overweight, Glucagon-Like Peptide 1
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 2026-10-11, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-11 (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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