The DOI matches its Crossref record, with a small difference in title or year; 53 of the 53 references it cites were found in a registry or an index; 2 of the 88 sources its claims cite were checked for support.
Semaglutide for the treatment of obesity
Open accessAbstract
Semaglutide is a glucagon-like peptide-1 receptor agonist that was recently approved by the US Food and Drug Administration for chronic weight management. This paper reviews data on the mechanism of action, weight-loss and cardiometabolic efficacy, and safety of semaglutide 2.4 mg/week for obesity. Semaglutide has demonstrated the largest weight loss of any obesity medication to date with reductions of approximately 15% of initial weight at 68 weeks, accompanied by improvements in cardiovascular risks factors and physical functioning. The approval of this medication provides patients with greater options for weight management.
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Claims the paper makes
62 Not checked yet · 6 Own interpretation · 1 Supported · 1 Partly supported · accuracy not yet measured
In the paper
“The mean weight loss was significantly greater with all doses of liraglutide relative to placebo (4.8 kg, 5.5 kg, 6.3 kg, and 7.2 kg for liraglutide 1.2 mg, 1.8 mg, 2.4 mg, and 3.0 mg, respectively, versus 2.8 kg for placebo).”
§ Semaglutide for the Treatment of Obesity > Liraglutide
What the sources say
- Not checked yetcites [17] Astrup, 2009, Effects of liraglutide in the treatment of obesity: a randomised, double-blind, placebo-controlled study, Lancet source
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.
In the paper
“Liraglutide induces weight loss by reducing energy intake.(16)”
§ Semaglutide for the Treatment of Obesity > Liraglutide
What the sources say
- Not checked yetcites [16] Van Can, 2014, Effects of the once-daily GLP-1 analog liraglutide on gastric emptying, glycemic parameters, appetite and energy metabolism in obese, non-diabetic adults, Int J Obes source
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.
In the paper
“Compared to placebo, liraglutide lowers ad libitum energy intake by 16%, as shown with a laboratory meal paradigm.(16)”
§ Semaglutide for the Treatment of Obesity > Liraglutide
What the sources say
- Not checked yetcites [16] Van Can, 2014, Effects of the once-daily GLP-1 analog liraglutide on gastric emptying, glycemic parameters, appetite and energy metabolism in obese, non-diabetic adults, Int J Obes source
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.
In the paper
“Participants who received liraglutide 2.4 mg or 3.0 mg also lost significantly more weight than those assigned to orlistat (4.1 kg).”
§ Semaglutide for the Treatment of Obesity > Liraglutide
What the sources say
- Not checked yetcites [17] Astrup, 2009, Effects of liraglutide in the treatment of obesity: a randomised, double-blind, placebo-controlled study, Lancet source
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.
In the paper
“Compared to placebo, semaglutide 2.4 mg (i.e., once-weekly for 20 weeks) reduced ad libitum energy intake by 35%, as shown with a laboratory meal paradigm.(30)”
§ Semaglutide for the Treatment of Obesity > Semaglutide > Mechanisms of Action for Weight Loss
What the sources say
- Not checked yetcites [30] Friedrichsen, 2021, 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 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Fully 32.0% of semaglutide-treated participants lost 20% or more of baseline weight, compared with only 1.7% of the placebo group.”
§ Semaglutide for the Treatment of Obesity > Semaglutide > Weight-Loss and Cardiometabolic Efficacy
What the sources say
- Not checked yetcites [34] Wilding, 2021
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.
In the paper
“However, only a very small proportion (<1 percentage point) of weight loss is explained by nausea or vomiting.(32)”
§ Semaglutide for the Treatment of Obesity > Semaglutide > Mechanisms of Action for Weight Loss
What the sources say
- Not checked yetcites [32] Wharton, 2021, Gastrointestinal tolerability of once-weekly semaglutide 2.4 mg in adults with overweight or obesity, and the relationship between gastrointestinal adverse events and weight loss, Diabetes Obes and Metab
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.
In the paper
“However, studies have shown that semaglutide tends to have minimal effects on gastric emptying.(30)”
§ Semaglutide for the Treatment of Obesity > Semaglutide > Mechanisms of Action for Weight Loss
What the sources say
- Not checked yetcites [30] Friedrichsen, 2021, 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 source
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.
In the paper
“Semaglutide results in weight loss via reduced energy intake with minimal effects on energy expenditure.(29)”
§ Semaglutide for the Treatment of Obesity > Semaglutide > Mechanisms of Action for Weight Loss
What the sources say
- Not checked yetcites [29] Blundell, 2017, Effects of once-weekly semaglutide on appetite, energy intake, control of eating, food preference and body weight in subjects with obesity, Diabetes Obes Metab source
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.
In the paper
“As measured from the start of the run-in period, the two groups achieved mean cumulative weight losses at week 68 of 17.4% and 5.7%, respectively (see Figures 2 and 3).”
§ Semaglutide for the Treatment of Obesity > Semaglutide > Weight-Loss and Cardiometabolic Efficacy
What the sources say
- Not checked yetcites [37] Rubino, 2021, Effect of continued weekly subcutaneous semaglutide vs placebo on weight loss maintenance in adults with overweight or obesity: the STEP 4 randomized clinical trial, JAMA source
plainn = 803- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- It may state two separate claims as one. 37
- Probably not a substantial claim. 9
Every source the paper cites for this claim was checked and supports it.
In the paper
“Continued semaglutide, relative to the switch to placebo, was associated with better outcomes for waist circumference, systolic blood pressure, hemoglobin A1c, fasting plasma glucose, fasting serum insulin, lipid profile, and physical functioning on the SF-36 (Table 1).”
§ Semaglutide for the Treatment of Obesity > Semaglutide > Weight-Loss and Cardiometabolic Efficacy
What the sources say
- Supportedcites [37] Rubino, 2021, Effect of continued weekly subcutaneous semaglutide vs placebo on weight loss maintenance in adults with overweight or obesity: the STEP 4 randomized clinical trial, JAMA source
The Confirmatory and Supportive Secondary End Points section reports better waist circumference, systolic blood pressure, HbA1c, fasting plasma glucose, lipid profile, and SF-36 physical functioning outcomes with continued semaglutide versus placebo. Table 2 also reports a greater reduction in fasting serum insulin with continued semaglutide (-18% versus 0%; P < .001). (LLM, conf=0.95)
plaincorrelationaln = 803 ·- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the 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.”
§ Semaglutide for the Treatment of Obesity > Semaglutide > Safety
What the sources say
- Not checked yetcites [34] Wilding, 2021
- Not checked yetcites [35] Davies, 2021, Semaglutide 2• 4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial, Lancet source
- Partly supportedcites [36] Wadden, 2021, 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, JAMA sourceExperimental — accuracy not yet measured
The Adverse Events section reports that gallbladder-related disorders, mainly cholelithiasis, occurred in 4.9% of semaglutide participants versus 1.5% of placebo participants in STEP 3. The paper’s passages do not provide the stated gallbladder-disorder percentages for STEP 1 or STEP 2, so this source supports only the STEP 3 portion of the sentence. 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: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The half-life of GLP-1 is 1 to 2 minutes due to N-terminal degradation by the enzyme dipeptidyl peptidase 4 (DPP-4).(8, 9)”
§ Semaglutide for the Treatment of Obesity > Introduction
What the sources say
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.
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
“Semaglutide has demonstrated the largest weight loss of any obesity medication to date with reductions of approximately 15% of initial weight at 68 weeks, accompanied by improvements in cardiovascular risks factors and physical functioning.”
§ Semaglutide for the Treatment of Obesity > Abstract
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Liraglutide, relative to placebo, resulted in declines of 15.7 mg/dL in fasting blood glucose, 0.5% in hemoglobin A1c, and 2.8 mmHg in systolic blood pressure.(24)”
§ Semaglutide for the Treatment of Obesity > Liraglutide
What the sources say
- Not checked yetcites [24] Khera, 2018, Effects of weight-loss medications on cardiometabolic risk profiles: a systematic review and network meta-analysis, Gastroenterology source
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.
None of the sources cited for this claim have been checked yet.
In the paper
“It stimulates insulin release and secretion in hyperglycemic states, inhibits glucagon release in hyperglycemic or euglycemic states, slows gastric emptying, and reduces food intake.(6, 7)”
§ Semaglutide for the Treatment of Obesity > Introduction
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“A meta-analysis showed that liraglutide produced a mean 5.2 kg placebo-subtracted weight loss at 1 year, with 63% of participants achieving a ≥5% weight loss, inclusive of 34% of participants who lost ≥10% of initial weight.(23)”
§ Semaglutide for the Treatment of Obesity > Liraglutide
What the sources say
- Not checked yetcites [23] Khera, 2016, Association of pharmacological treatments for obesity with weight loss and adverse events: a systematic review and meta-analysis, JAMA source
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.
In the paper
“Weight losses of 5% or more of initial weight help to ameliorate these complications, with larger losses producing greater health benefits.(3)”
§ Semaglutide for the Treatment of Obesity > Introduction
What the sources say
- Not checked yetcites [3] 2013, Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes, NEJM source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Glucagon-like peptide 1 (GLP-1) is a hormone released from the proglucagon gene in L-cells of the distal small intestine and colon in response to oral nutrient intake.(5)”
§ Semaglutide for the Treatment of Obesity > Introduction
What the sources say
- Not checked yetcites [5] Koliaki, 2011, Incretin-based therapy: a powerful and promising weapon in the treatment of type 2 diabetes mellitus, Diabetes Ther 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.
In the paper
“It has little known effect on energy expenditure.(16)”
§ Semaglutide for the Treatment of Obesity > Liraglutide
What the sources say
- Not checked yetcites [16] Van Can, 2014, Effects of the once-daily GLP-1 analog liraglutide on gastric emptying, glycemic parameters, appetite and energy metabolism in obese, non-diabetic adults, Int J Obes source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“The hormone binds to GLP-1 receptors expressed in tissues such as the pancreatic beta cells, gastric mucosa, kidney, heart, and hypothalamus.(6, 7)”
§ Semaglutide for the Treatment of Obesity > Introduction
What the sources say
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.
In the paper
“Semaglutide-treated participants, relative to placebo, achieved larger reductions in waist circumference, systolic and diastolic blood pressure, hemoglobin A1c, fasting blood glucose, total cholesterol, LDL cholesterol, triglycerides, and c-reactive protein.”
- Also stated in: § Weight-Loss and Cardiometabolic Efficacy · plain
“They also experienced greater improvements in HDL cholesterol, and in physical functioning as assessed by the 36-item Short Form Health Survey (SF-36) and by the Impact of Weight on Quality of Life–Lite Clinical Trials Version (IWQOL-Lite-CT) questionnaires (Table 1).”
§ Semaglutide for the Treatment of Obesity > Semaglutide > Weight-Loss and Cardiometabolic Efficacy
What the sources say
- Not checked yetcites [34] Wilding, 2021
plaindirectn = 1,961- 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.
- Also stated in: § Weight-Loss and Cardiometabolic Efficacy · plain
None of the sources cited for this claim have been checked yet.
In the paper
“This formulation results in slower degradation and a half-life 155 to 184 hours, allowing for once-weekly subcutaneous dosing without compromising weight loss efficacy.(11, 26)”
§ Semaglutide for the Treatment of Obesity > Semaglutide > Mechanisms of Action for Weight Loss
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“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).”
§ Semaglutide for the Treatment of Obesity > Semaglutide > Weight-Loss and Cardiometabolic Efficacy
What the sources say
- Not checked yetcites [36] Wadden, 2021, 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, JAMA source
plaindirectn = 611- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“It has structural modifications to allow for reversible albumin binding, reducing renal clearance and decreasing degradation by DPP-4, while also allowing for sufficiently high GLP-1R affinity.(11, 26)”
§ Semaglutide for the Treatment of Obesity > Semaglutide > Mechanisms of Action for Weight Loss
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Most gastrointestinal events were mild-to-moderate in severity, transient, and occurred during the first 20 weeks of treatment during dose escalation.”
§ Semaglutide for the Treatment of Obesity > Semaglutide > Safety
What the sources say
- Not checked yetcites [34] Wilding, 2021
- Not checked yetcites [35] Davies, 2021, Semaglutide 2• 4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial, Lancet source
- Not checked yetcites [36] Wadden, 2021, 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, JAMA source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Semaglutide promotes insulin secretion from beta cells in the pancreas and decreases glucagon secretion in a glucose-dependent manner.(27, 28)”
§ Semaglutide for the Treatment of Obesity > Semaglutide > Mechanisms of Action for Weight Loss
What the sources say
- Not checked yetcites [27] Ahmann, 2018, 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 source
- Not checked yetcites [28] Ahrén, 2017, 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 source
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.
None of the sources cited for this claim have been checked yet.
In the 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%.”
§ Semaglutide for the Treatment of Obesity > Semaglutide > Safety
What the sources say
- Not checked yetcites [34] Wilding, 2021
- Not checked yetcites [35] Davies, 2021, Semaglutide 2• 4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial, Lancet source
- Not checked yetcites [36] Wadden, 2021, 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, JAMA 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.
It may state two separate claims as one.
In the paper
“Those who remained on semaglutide lost 7.9 percentage points of their randomization weight from weeks 20 to 68, whereas those switched to placebo gained 6.9 percentage points (estimated treatment differences = −14.8; 95% CI=−16.0 to −13.5 percentage points; p<0.001).”
§ Semaglutide for the Treatment of Obesity > Semaglutide > Weight-Loss and Cardiometabolic Efficacy
What the sources say
- Not checked yetcites [37] Rubino, 2021, Effect of continued weekly subcutaneous semaglutide vs placebo on weight loss maintenance in adults with overweight or obesity: the STEP 4 randomized clinical trial, JAMA source
plaindirectn = 803 ·- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Significantly more participants in the semaglutide than in the placebo group achieved reductions of ≥5%, ≥10%, and ≥15% (Figure 3).”
§ Semaglutide for the Treatment of Obesity > Semaglutide > Weight-Loss and Cardiometabolic Efficacy
What the sources say
- Not checked yetcites [34] Wilding, 2021
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“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).”
§ Semaglutide for the Treatment of Obesity > Semaglutide > Weight-Loss and Cardiometabolic Efficacy
What the sources say
- Not checked yetcites [36] Wadden, 2021, 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, JAMA source
plaindirectn = 611- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The estimated treatment difference for semaglutide 2.4 mg vs placebo was −6.2 percentage points (95% CI −7.3 to −5.2, p<0.001), and for semaglutide 2.4 mg vs semaglutide 1.0 mg was 2.7 percentage points (95% CI −3.7 to −1.6, p<0.0001).”
§ Semaglutide for the Treatment of Obesity > Semaglutide > Weight-Loss and Cardiometabolic Efficacy
What the sources say
- Not checked yetcites [35] Davies, 2021, Semaglutide 2• 4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial, Lancet source
plainn = 1,210 ·- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Semaglutide is a long-acting GLP-1 receptor agonist with 94 percent homology with native human GLP-1.”
§ Semaglutide for the Treatment of Obesity > Semaglutide > Mechanisms of Action for Weight Loss
What the sources say
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.
In the paper
“Semaglutide-treated patients lost 14.9% of baseline weight compared with 2.4% for placebo (estimated treatment difference = −12.4 percentage points, 95% CI −13.4 to −11.5; Table 1).”
§ Semaglutide for the Treatment of Obesity > Semaglutide > Weight-Loss and Cardiometabolic Efficacy
What the sources say
- Not checked yetcites [34] Wilding, 2021
plaindirectn = 1,961- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The semaglutide 2.4 mg group, compared with placebo, had significantly greater reductions in waist circumference, A1c, fasting glucose, systolic blood pressure, triglycerides, c-reactive protein, and physical functioning scores on the SF-36 and IWQOL-Lite-CT (Table 1).”
§ Semaglutide for the Treatment of Obesity > Semaglutide > Weight-Loss and Cardiometabolic Efficacy
What the sources say
- Not checked yetcites [35] Davies, 2021, Semaglutide 2• 4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial, Lancet source
plaindirectn = 1,210 ·- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Cholelithiasis formation may also be a result of the direct action of GLP-1 and its agonist on biliary secretion and/or drug-induced modification of gallbladder motility.(56)”
§ Semaglutide for the Treatment of Obesity > Discussion
What the sources say
- Not checked yetcites [56] Nexøe-Larsen, 2018, Effects of liraglutide on gallbladder emptying: A randomized, placebo-controlled trial in adults with overweight or obesity, Diabetes Obes Metab source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“STEP 4 revealed two very important findings, the first which is that patients will lose substantial amounts of weight during the 16-week upward titration period but will not achieve their maximum weight loss until taking the full dose for 1 year.”
§ Semaglutide for the Treatment of Obesity > Discussion
What the sources say
- Not checked yetcites [37] Rubino, 2021, Effect of continued weekly subcutaneous semaglutide vs placebo on weight loss maintenance in adults with overweight or obesity: the STEP 4 randomized clinical trial, JAMA source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
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
“While participants only need to inject themselves once a week, this may limit use for some individuals who are reluctant to inject a medication.”
§ Semaglutide for the Treatment of Obesity > Discussion
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Mechanisms responsible for smaller weight losses in patients with diabetes may include reductions in resting metabolic rate, which occur with improved glycemic control (accompanying weight loss), decreased dietary adherence and “defensive snacking” related to fears of hypoglycemia, as well as reduced glycosuria.(49, 50)”
§ Semaglutide for the Treatment of Obesity > Discussion
What the sources say
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.
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
“More than half of participants in STEP 1 lost 15% or more of baseline weight, and 30% of participants lost 20% of initial weight, a loss that approaches that produced by sleeve gastrectomy.”
§ Semaglutide for the Treatment of Obesity > Discussion
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“They could be the result of the effect of the medication on gastrointestinal functions such as gastric emptying, intestinal motility, secondary changes in the secretion of other gastrointestinal peptide hormones, and/or direct or indirect effects on the central nervous system.(51)”
§ Semaglutide for the Treatment of Obesity > Discussion
What the sources say
- Not checked yetcites [51] Baraboi, 2011, Brain activation following peripheral administration of the GLP-1 receptor agonist exendin-4, Am J Physiol Regul Integr Comp Physiol source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“STEP 1 found that semaglutide increased this value to 12.5 kg, with a mean 14.9% reduction in baseline weight at 68 weeks, compared with to 7%−8% for most other AOM.”
§ Semaglutide for the Treatment of Obesity > Discussion
What the sources say
- Not checked yetcites [34] Wilding, 2021
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.
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 oral formulation may improve convenience, acceptance, and adherence.”
§ Semaglutide for the Treatment of Obesity > Discussion
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“The exact mechanism of development of cholelithiasis in GLP1-RAs is unknown but may be attributable to large, rapid weight losses experienced by some patients.(53)”
§ Semaglutide for the Treatment of Obesity > Discussion
What the sources say
- Not checked yetcites [53] Erlinger, 2000, Gallstones in obesity and weight loss, Eur J Gastroenterol Hepatol source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“The primary composite outcome -- death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke -- occurred in significantly fewer participants treated by semaglutide (6.6%) than by placebo (8.9%) (HR, 0.74; 95% CI, 0.58 to 0.95; p<0.001 for noninferiority; p=0.02 for superiority).”
§ Semaglutide for the Treatment of Obesity > Semaglutide > Cardiovascular Safety
What the sources say
- Not checked yetcites [39] Marso, 2016, Semaglutide and cardiovascular outcomes in patients with type 2 diabetes, NEJM source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“However, the week-68 loss of 9.6% was approximately one-third less than that observed in participants without diabetes in the three other STEP trials reviewed.”
§ Semaglutide for the Treatment of Obesity > Discussion
What the sources say
- Not checked yetcites [35] Davies, 2021, Semaglutide 2• 4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial, Lancet 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.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Greater weight loss reliably produces greater improvements in several cardiometabolic risk factors,(3) as well as quality of life,(41) as was observed in the STEP trials.”
§ Semaglutide for the Treatment of Obesity > Discussion
What the sources say
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“As with all GLP-1 medications, gastrointestinal side effects were common in participants who took semaglutide 2.4 mg, though most were mild-to-moderate, and the majority of participants recovered without treatment discontinuation.”
§ Semaglutide for the Treatment of Obesity > Discussion
What the sources say
- Not checked yetcites [32] Wharton, 2021, Gastrointestinal tolerability of once-weekly semaglutide 2.4 mg in adults with overweight or obesity, and the relationship between gastrointestinal adverse events and weight loss, Diabetes Obes and Metab
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.
None of the sources cited for this claim have been checked yet.
In the paper
“Several studies in patients with type 2 diabetes (in different countries) have shown absolute cost savings with semaglutide 1.0 mg, as well as the cost effectiveness of semaglutide 1.0 mg compared to other diabetes pharmacotherapies.(58, 59)”
§ Semaglutide for the Treatment of Obesity > Discussion
What the sources say
- Not checked yetcites [58] Viljoen, 2019, Evaluation of the long-term cost-effectiveness of once-weekly semaglutide versus dulaglutide for treatment of type 2 diabetes mellitus in the UK, Diabetes Obes Metab source
- Not checked yetcites [59] Wilkinson, 2018, Cost of achieving HbA1c treatment targets and weight loss responses with once-weekly semaglutide versus dulaglutide in the United States, Diabetes Ther source
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.
In the paper
“Thus, the study did not suggest the occurrence of fully additive weight loss, which had been observed when IBT was combined with AOM that produced a mean reduction of only 5%−6% of initial weight.(43)”
§ Semaglutide for the Treatment of Obesity > Discussion
What the sources say
- Not checked yetcites [43] Wadden, 2005, Randomized trial of lifestyle modification and pharmacotherapy for obesity, NEJM source
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“HbA1c improved markedly in both groups – by 1.5–1.6% - but did not differ significantly, affirming the different doses prescribed for the management of obesity vs type 2 diabetes.”
§ Semaglutide for the Treatment of Obesity > Discussion
What the sources say
- Not checked yetcites [35] Davies, 2021, Semaglutide 2• 4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial, Lancet source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“However, few cost evaluations have been conducted for AOM specifically for weight management; one study suggested that semaglutide may not be cost-effective because of its high price.(60)”
§ Semaglutide for the Treatment of Obesity > Discussion
What the sources say
- Not checked yetcites [60] Lee, 2020, The cost-effectiveness of pharmacotherapy and lifestyle intervention in the treatment of obesity, Obes Sci Pract 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.
The paper relies on this without support.
Comprehensive lifestyle intervention remains the cornerstone of obesity treatment, but suboptimal weight losses and weight regain are common with this approach.
“Comprehensive lifestyle intervention remains the cornerstone of obesity treatment, but suboptimal weight losses and weight regain are common with this approach.”
The paper relies on this without support.
The efficacy and safety results from the STEP trials apply to the broader population of adults with obesity or overweight.
“Taken together, the first four STEP trials have revealed several critical findings concerning the induction and maintenance of weight loss.”
The paper relies on this without support.
The cardiovascular outcome results from SUSTAIN-6 with semaglutide 0.5 or 1.0 mg in patients with type 2 diabetes apply to semaglutide 2.4 mg in patients with obesity without diabetes.
“The small mean increase in pulse rate does not appear to adversely affect cardiovascular outcomes, as revealed by results of the Trial to Evaluate Cardiovascular and Other Long-term Outcomes with Semaglutide in Subjects with Type 2 Diabetes (SUSTAIN-6).(39)”
The paper relies on this without support.
For most people, obesity is a chronic condition that can be managed but not cured.
“with the recognition that obesity, for most individuals, is a chronic condition that can be managed by not cured.”
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 says what the claim attributes to it.
In the citing paper
“Semaglutide, administered once weekly at a dose of 2.4 mg, has demonstrated significant weight loss outcomes in clinical trials, with reductions in body weight exceeding 15% in many patients. 5 , 6”
From Impact of Semaglutide on fat mass, lean mass and muscle function in patients with obesity: The SEMALEAN study (2026) · cites this paper as [5]
In the citing paper
“It effectively lowers glucose levels and promotes significant weight loss, making it widely adopted for the treatment of diabetes and obesity.3,4”
From Semaglutide Therapy and Accelerated Sarcopenia in Older Adults with Type 2 Diabetes: A 24-Month Retrospective Cohort Study (2025) · cites this paper as [4]
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
§ Semaglutide for the Treatment of Obesity > Introduction
“Five medications are currently approved for weight management in the US”
§ Semaglutide for the Treatment of Obesity > Introduction
“(liraglutide, orlistat, phentermine, naltrexone/bupropion, phentermine/topiramate, and semaglutide)”
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
§ Semaglutide for the Treatment of Obesity > Semaglutide > Weight-Loss and Cardiometabolic Efficacy
“for semaglutide 2.4 mg vs semaglutide 1.0 mg was 2.7 percentage points”
§ Semaglutide for the Treatment of Obesity > Semaglutide > Weight-Loss and Cardiometabolic Efficacy
“95% CI −3.7 to −1.6”
Citations
Cites
Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes
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Once-Weekly Semaglutide in Adults with Overweight or Obesity
Wilding, J. P. H., Batterham, R. L., Calanna, S., Davies, M., Van Gaal, L. F., Lingvay, I., McGowan, B. M., Rosenstock, J., Tran, M. T. D., Wadden, T. A., et al. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2032183 · Cited by 5,205
Self-citationThe Physiology of Glucagon-like Peptide 1
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Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes
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Self-citationA Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management
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Cholelithiasis in patients treated with a very-low-calorie diet
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Pearl, R. L., Wadden, T. A., Tronieri, J. S., Berkowitz, R. I., Chao, A. M., Alamuddin, N., Leonard, S. M., Carvajal, R., Bakizada, Z. M., Pinkasavage, E., et al. (2018) · Obesity · doi:10.1002/oby.22187 · Cited by 38
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Is Type 2 Diabetes in Adults Associated With Impaired Capacity for Weight Loss?
Antoun, G., Nikpay, M., McPherson, R., Harper, M., & Dent, R. (2017) · Canadian Journal of Diabetes · doi:10.1016/j.jcjd.2017.06.010 · Cited by 6
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Cited by
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Once-Weekly Semaglutide in Adults With Alcohol Use Disorder: A Randomized Clinical Trial
Hendershot, C. S., Bremmer, M. P., Paladino, M. B., Kostantinis, G., Gilmore, T. A., Sullivan, N. R., Tow, A. C., Dermody, S. S., Prince, M. A., Jordan, R., et al. (2025) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2024.4789 · Cited by 287
Wadden, T. A., Chao, A. M., Moore, M., Tronieri, J. S., Gilden, A., Amaro, A., Leonard, S., & Jakicic, J. M. (2023) · Current Obesity Reports · doi:10.1007/s13679-023-00534-z · Cited by 129
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A systematic review of the effect of semaglutide on lean mass: insights from clinical trials
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“Existing pharmaceutical interventions for obesity management like orlistat, naltrexone-bupropion, and glucagon-like peptide-1 receptor agonists (GLP1-RAs), including liraglutide and semaglutide, have received approvals from both the FDA and the EMA [7].”
BackgroundSpotlight on the Mechanism of Action of Semaglutide
Papakonstantinou, I. P., Tsioufis, K. P., & Katsi, V. K. (2024) · Current Issues in Molecular Biology · doi:10.3390/cimb46120872 · Cited by 89
“The body weight reduction in people with obesity with semaglutide 2.4 mg once weekly is approximately 15%, with simultaneous improvement in cardiometabolic risk factors and physical functioning [10,11].”
Influential
Metadata
- Authors
- Chao, A. M., Tronieri, J. S., Amaro, A., & Wadden, T. A.
- Affiliations
- University of Pennsylvania (US)
- Corresponding author
- Chao, Ariana M.
- Venue
- Trends in Cardiovascular Medicine
- Publisher
- Elsevier BV
- Published
- 2023-04
- Volume
- 33
- Issue
- 3
- Pages
- 159-166
- ISSN
- 1050-1738 (ISSN-L)
- PMC
- PMC9209591
- OpenAlex
- W4200213833
- Cited by
- 227
- References
- 50
- Citations by year
- 2026: 71 · 2025: 83 · 2024: 48 · 2023: 19
- FWCI
- 2.31
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Trends in Cardiovascular Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Nursing Research
- National Institutes of Health (K23NR017209)
- 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, GLP-1 receptor agonists, weight loss, cardiometabolic risk, cardiovascular risk factors, drug safety, mechanism of action, weight management
- MeSH terms
- Semaglutide, Diabetes Mellitus, Type 2, Glucagon-Like Peptides, Humans, Hypoglycemic Agents, Obesity, Weight Loss
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.
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Statistics and arithmetic are recomputed, not judged.
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