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Efficacy of GLP-1 RA Approved for Weight Management in Patients With or Without Diabetes: A Narrative Review
Open accessAbstract
The approval of once daily liraglutide, 3.0 mg, and once weekly semaglutide, 2.4 mg, for chronic weight management provides a novel effective strategy against obesity. The reliable models that might predict weight reducing potential at the individual level have not been identified yet. However, the coexistence of diabetes has been consistently related with less effective response than in people without this comorbidity. We aimed to review the efficacy of GLP-1 RAs approved for weight management in individuals with and without diabetes and discuss some potential mechanisms for consistently observed differences in efficacy between these two populations. The mean weight loss difference between GLP-1 RAs and placebo as add-on to lifestyle intervention in patients with diabetes was 4% to 6.2% compared to 6.1 to 17.4% in people without diabetes. Semaglutide compared to liraglutide resulted in greater weight loss. Some hypothetical explanations for the weaker anti-obesity response for both GLP-1 RAs in people with diabetes include the background medications that promote weight gain, the fear of hypoglycaemia inherently related to the treatment of diabetes, a decrease in glycosuria and subsequently less weight loss in diabetics, an altered microbiota in patients with obesity and diabetes and a genetic background that predispose to weight gain in patients with diabetes. Moreover, people with diabetes may have had obesity for longer and may be less adherent to exercise, which seems to potentiate the effects of GLP-1 RA. Emerging multimodal approaches combining peptides targeting receptors at different levels might therefore be of additional benefit particularly in patients with diabetes.
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In the paper
“However, the coexistence of diabetes has been consistently related with less effective response than in people without this comorbidity.”
- Also stated in: § Introduction · boosted
“However, the coexistence of diabetes has been consistently related with less weight loss under medication than in patients without diabetes.”
- Also stated in: § Conclusion · boosted
“It is established that people with diabetes have more difficulty losing weight than individuals without diabetes and differences between individuals with and without diabetes were consistently confirmed also for GLP-1RAs.”
§ Efficacy of GLP-1 RA Approved for Weight Management in Patients With or Without Diabetes: A Narrative Review > Abstract
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- Also stated in: § Introduction · boosted
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In the paper
“In summary, participants without diabetes treated with high-dose liraglutide and semaglutide reached both efficacy-benchmark criteria.”
§ Efficacy of GLP-1 RA Approved for Weight Management in Patients With or Without Diabetes: A Narrative Review > Results > Trial on Semaglutide vs. Liraglutide in Persons Without Diabetes
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In the paper
“Both critera were met in phase 2 study [14], SCALE Obesity and Predabetes [10] and SCALE Maintenance [11] trials.”
§ Efficacy of GLP-1 RA Approved for Weight Management in Patients With or Without Diabetes: A Narrative Review > Results > Trials on Liraglutide in Persons Without Diabetes
What the sources say
- Not checked yetcites [14] Astrup A, Rössner S, Van Gaal L, Rissanen A, Niskanen L, Al Hakim M, Madsen J, Rasmussen MF, Lean ME; NN8022–1807 study group. Effects of liraglutide in the treatment of obesity: a randomised, double-blind, placebo-controlled study. Lancet. 2009; 374:1606–1616. source
- Not checked yetcites [10] Pi-Sunyer X, Astrup A, Fujioka K, Greenway F, Halpern A, Krempf M, et al; SCALE obesity and prediabetes NN8022–1839 study group. a randomized, controlled trial of 3.0 mg of liraglutide in weight management. N Engl J Med. 2015; 373:11–22. source
- Not checked yetcites [11] Wadden TA, Hollander P, Klein S, Niswender K, Woo V, Hale PM, et al; NN8022–1923 Investigators. Weight maintenance and additional weight loss with liraglutide after low-calorie-diet-induced weight loss: the SCALE Maintenance randomized study. Int J Obes (Lond). 2013; 37:1443–1451. source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“While some patients with diabetes achieved ≥ 5 or 10% with placebo, higher levels of ≥ 15% in patients with diabetes were achieved almost exclusively with those who received liraglutide or semaglutide and not by those on placebo [20–22].”
- Also stated in: § Conclusion · boosted
“However, higher levels of weight loss of ≥ 15% were achieved almost exclusively by participants with diabetes who received liraglutide or semaglutide, whereas this outcome has not been attainable by any other glucose-lowering intervention or with lifestyle intervention alone.”
§ Efficacy of GLP-1 RA Approved for Weight Management in Patients With or Without Diabetes: A Narrative Review > Results > Trial on Semaglutide vs. Liraglutide in Persons Without Diabetes
What the sources say
- Not checked yetcites [20] Davies MJ, Bergenstal R, Bode B, et al.; NN8022–1922 Study Group. Efficacy of liraglutide for weight loss among patients with type 2 diabetes: the scale diabetes randomized clinical trial. JAMA. 2015; 314:687–699. source
- Not checked yetcites [21] Garvey WT, Birkenfeld AL, Dicker D, et al. Efficacy and safety of liraglutide 3.0 mg in individuals with overweight or obesity and type 2 diabetes treated with basal insulin: the SCALE insulin randomized controlled trial. Diabetes Care. 2020;43:1085–93. source
- Not checked yetcites [22] Davies M, Færch L, Jeppesen OK, et al.; STEP 2 Study Group. 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. 2021; 397:971–984. source
boosteddirect- Asserted: passes — The authors put it forward as true.
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- Also stated in: § Conclusion · boosted
None of the sources cited for this claim have been checked yet.
In the paper
“Liraglutide resulted in 3.4 to 6.1% difference in mean weight loss compared to placebo [10–14, 19].”
§ Efficacy of GLP-1 RA Approved for Weight Management in Patients With or Without Diabetes: A Narrative Review > Results > Trials on Liraglutide in Persons Without Diabetes
What the sources say
- Not checked yetcites [10] Pi-Sunyer X, Astrup A, Fujioka K, Greenway F, Halpern A, Krempf M, et al; SCALE obesity and prediabetes NN8022–1839 study group. a randomized, controlled trial of 3.0 mg of liraglutide in weight management. N Engl J Med. 2015; 373:11–22. source
- Not checked yetcites [11] Wadden TA, Hollander P, Klein S, Niswender K, Woo V, Hale PM, et al; NN8022–1923 Investigators. Weight maintenance and additional weight loss with liraglutide after low-calorie-diet-induced weight loss: the SCALE Maintenance randomized study. Int J Obes (Lond). 2013; 37:1443–1451. source
- Not checked yetcites [12] Blackman A, Foster GD, Zammit G, Rosenberg R, Aronne L, Wadden T, Claudius B, Jensen CB, Mignot E. Effect of liraglutide 3.0 mg in individuals with obesity and moderate or severe obstructive sleep apnea: the SCALE Sleep Apnea randomized clinical trial. Int J Obes (Lond). 2016; 40:1310–1319. source
- Not checked yetcites [13] Wadden TA, Tronieri JS, Sugimoto D, Lund MT, Auerbach P, Jensen C, Rubino D. Liraglutide 3.0 mg and intensive behavioral therapy (IBT) for obesity in primary care: the SCALE IBT randomized controlled trial. Obesity (Silver Spring). 2020; 28:529–536. source
- Not checked yetcites [14] Astrup A, Rössner S, Van Gaal L, Rissanen A, Niskanen L, Al Hakim M, Madsen J, Rasmussen MF, Lean ME; NN8022–1807 study group. Effects of liraglutide in the treatment of obesity: a randomised, double-blind, placebo-controlled study. Lancet. 2009; 374:1606–1616. source
- Not checked yetcites [19] Rubino DM, Greenway FL, Khalid U, et al; STEP 8 Investigators. Effect of weekly subcutaneous semaglutide vs daily liraglutide on body weight in adults with overweight or obesity without diabetes: the STEP 8 randomized clinical trial. JAMA. 2022; 327:138–150. 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
“Semaglutide compared to liraglutide resulted in greater weight loss.”
- Also stated in: § Trial on Semaglutide vs. Liraglutide in Persons Without Diabetes · boosted
“The STEP 8 trial found that weight loss with semaglutide was significantly greater than with liraglutide in adults with overweight or obesity without diabetes [19].”
§ Efficacy of GLP-1 RA Approved for Weight Management in Patients With or Without Diabetes: A Narrative Review > Abstract
What the sources say
- Not checked yetcites [19] Rubino DM, Greenway FL, Khalid U, et al; STEP 8 Investigators. Effect of weekly subcutaneous semaglutide vs daily liraglutide on body weight in adults with overweight or obesity without diabetes: the STEP 8 randomized clinical trial. JAMA. 2022; 327:138–150. source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Trial on Semaglutide vs. Liraglutide in Persons Without Diabetes · boosted
None of the sources cited for this claim have been checked yet.
In the paper
“The proportion of subjects who lost ≥ 5% of baseline body weight was 50.5–73% [10–14, 19].”
§ Efficacy of GLP-1 RA Approved for Weight Management in Patients With or Without Diabetes: A Narrative Review > Results > Trials on Liraglutide in Persons Without Diabetes
What the sources say
- Not checked yetcites [10] Pi-Sunyer X, Astrup A, Fujioka K, Greenway F, Halpern A, Krempf M, et al; SCALE obesity and prediabetes NN8022–1839 study group. a randomized, controlled trial of 3.0 mg of liraglutide in weight management. N Engl J Med. 2015; 373:11–22. source
- Not checked yetcites [11] Wadden TA, Hollander P, Klein S, Niswender K, Woo V, Hale PM, et al; NN8022–1923 Investigators. Weight maintenance and additional weight loss with liraglutide after low-calorie-diet-induced weight loss: the SCALE Maintenance randomized study. Int J Obes (Lond). 2013; 37:1443–1451. source
- Not checked yetcites [12] Blackman A, Foster GD, Zammit G, Rosenberg R, Aronne L, Wadden T, Claudius B, Jensen CB, Mignot E. Effect of liraglutide 3.0 mg in individuals with obesity and moderate or severe obstructive sleep apnea: the SCALE Sleep Apnea randomized clinical trial. Int J Obes (Lond). 2016; 40:1310–1319. source
- Not checked yetcites [13] Wadden TA, Tronieri JS, Sugimoto D, Lund MT, Auerbach P, Jensen C, Rubino D. Liraglutide 3.0 mg and intensive behavioral therapy (IBT) for obesity in primary care: the SCALE IBT randomized controlled trial. Obesity (Silver Spring). 2020; 28:529–536. source
- Not checked yetcites [14] Astrup A, Rössner S, Van Gaal L, Rissanen A, Niskanen L, Al Hakim M, Madsen J, Rasmussen MF, Lean ME; NN8022–1807 study group. Effects of liraglutide in the treatment of obesity: a randomised, double-blind, placebo-controlled study. Lancet. 2009; 374:1606–1616. source
- Not checked yetcites [19] Rubino DM, Greenway FL, Khalid U, et al; STEP 8 Investigators. Effect of weekly subcutaneous semaglutide vs daily liraglutide on body weight in adults with overweight or obesity without diabetes: the STEP 8 randomized clinical trial. JAMA. 2022; 327:138–150. 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.
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None of the sources cited for this claim have been checked yet.
In the paper
“The proportion of subjects who lost ≥ 5% of baseline body weight was 86.4–88.7% [15–17, 19].”
§ Efficacy of GLP-1 RA Approved for Weight Management in Patients With or Without Diabetes: A Narrative Review > Results > Trials on Semaglutide in Persons Without Diabetes
What the sources say
- Not checked yetcites [15] Wilding JPH, Batterham RL, Calanna S, et al.; STEP 1 Study group. Once-weekly semaglutide in adults with overweight or obesity. N Engl J Med. 2021; 384(11):989. source
- Not checked yetcites [16] Wadden TA, Bailey TS, Billings LK, et al.; STEP 3 Investigators. 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. 2021; 325:1403–1413. source
- Not checked yetcites [17] Rubino D, Abrahamsson N, Davies M, et al.; STEP 4 Investigators. 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. 2021; 325:1414–1425. source
- Not checked yetcites [19] Rubino DM, Greenway FL, Khalid U, et al; STEP 8 Investigators. Effect of weekly subcutaneous semaglutide vs daily liraglutide on body weight in adults with overweight or obesity without diabetes: the STEP 8 randomized clinical trial. JAMA. 2022; 327:138–150. 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.
None of the sources cited for this claim have been checked yet.
In the paper
“Both efficacy benchmark criteria for weight management products were met in STEP 1, 3, 4 and 8 trials [15–17, 19].”
§ Efficacy of GLP-1 RA Approved for Weight Management in Patients With or Without Diabetes: A Narrative Review > Results > Trials on Semaglutide in Persons Without Diabetes
What the sources say
- Not checked yetcites [15] Wilding JPH, Batterham RL, Calanna S, et al.; STEP 1 Study group. Once-weekly semaglutide in adults with overweight or obesity. N Engl J Med. 2021; 384(11):989. source
- Not checked yetcites [16] Wadden TA, Bailey TS, Billings LK, et al.; STEP 3 Investigators. 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. 2021; 325:1403–1413. source
- Not checked yetcites [17] Rubino D, Abrahamsson N, Davies M, et al.; STEP 4 Investigators. 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. 2021; 325:1414–1425. source
- Not checked yetcites [19] Rubino DM, Greenway FL, Khalid U, et al; STEP 8 Investigators. Effect of weekly subcutaneous semaglutide vs daily liraglutide on body weight in adults with overweight or obesity without diabetes: the STEP 8 randomized clinical trial. JAMA. 2022; 327:138–150. source
plain- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“Semaglutide resulted in 10.3–17.4% difference in mean weight compared to placebo [15–17, 19].”
§ Efficacy of GLP-1 RA Approved for Weight Management in Patients With or Without Diabetes: A Narrative Review > Results > Trials on Semaglutide in Persons Without Diabetes
What the sources say
- Not checked yetcites [15] Wilding JPH, Batterham RL, Calanna S, et al.; STEP 1 Study group. Once-weekly semaglutide in adults with overweight or obesity. N Engl J Med. 2021; 384(11):989. source
- Not checked yetcites [16] Wadden TA, Bailey TS, Billings LK, et al.; STEP 3 Investigators. 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. 2021; 325:1403–1413. source
- Not checked yetcites [17] Rubino D, Abrahamsson N, Davies M, et al.; STEP 4 Investigators. 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. 2021; 325:1414–1425. source
- Not checked yetcites [19] Rubino DM, Greenway FL, Khalid U, et al; STEP 8 Investigators. Effect of weekly subcutaneous semaglutide vs daily liraglutide on body weight in adults with overweight or obesity without diabetes: the STEP 8 randomized clinical trial. JAMA. 2022; 327:138–150. source
plaindirect- Asserted: passes — The authors put it forward as true.
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- It may state two separate claims as one. 16
- Probably not a substantial claim. 2
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The mean weight loss difference between GLP-1 RAs and placebo as add-on to lifestyle intervention in patients with diabetes was 4% to 6.2% compared to 6.1 to 17.4% in people without diabetes.”
- Also stated in: § Conclusion · plain
“The mean weight loss difference between GLP-1 RAs and placebo in patients with diabetes was 4–6.2% compared to 6.1 up to 17.4% in individuals without diabetes.”
§ Efficacy of GLP-1 RA Approved for Weight Management in Patients With or Without Diabetes: A Narrative Review > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Also stated in: § Conclusion · plain
None of the sources cited for this claim have been checked yet.
In the paper
“In patients with diabetes, both efficacy benchmarks were achieved by semaglutide [22], while the efficacy of liraglutide did not meet the criteria in mean difference between active product vs. placebo [20, 21].”
§ Efficacy of GLP-1 RA Approved for Weight Management in Patients With or Without Diabetes: A Narrative Review > Results > Trial on Semaglutide vs. Liraglutide in Persons Without Diabetes
What the sources say
- Not checked yetcites [22] Davies M, Færch L, Jeppesen OK, et al.; STEP 2 Study Group. 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. 2021; 397:971–984. source
- Not checked yetcites [20] Davies MJ, Bergenstal R, Bode B, et al.; NN8022–1922 Study Group. Efficacy of liraglutide for weight loss among patients with type 2 diabetes: the scale diabetes randomized clinical trial. JAMA. 2015; 314:687–699. source
- Not checked yetcites [21] Garvey WT, Birkenfeld AL, Dicker D, et al. Efficacy and safety of liraglutide 3.0 mg in individuals with overweight or obesity and type 2 diabetes treated with basal insulin: the SCALE insulin randomized controlled trial. Diabetes Care. 2020;43:1085–93. source
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“In both trials the difference in mean weight loss between the liraglutide and placebo-treated groups was < 5% after 1 year of treatment, but the proportion of subjects who lost ≥ 5% of baseline body weight in the liraglutide group was > 35%, from 51.8 to 54.3% [20, 21].”
§ Efficacy of GLP-1 RA Approved for Weight Management in Patients With or Without Diabetes: A Narrative Review > Results > Trials on Liraglutide in Persons with Diabetes
What the sources say
- Not checked yetcites [20] Davies MJ, Bergenstal R, Bode B, et al.; NN8022–1922 Study Group. Efficacy of liraglutide for weight loss among patients with type 2 diabetes: the scale diabetes randomized clinical trial. JAMA. 2015; 314:687–699. source
- Not checked yetcites [21] Garvey WT, Birkenfeld AL, Dicker D, et al. Efficacy and safety of liraglutide 3.0 mg in individuals with overweight or obesity and type 2 diabetes treated with basal insulin: the SCALE insulin randomized controlled trial. Diabetes Care. 2020;43:1085–93. source
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
In the paper
“Both efficacy benchmark criteria for weight management products were met in a STEP 2 trial [22]. Semaglutide resulted in 6.2% difference in mean weight loss vs. placebo [22]. The proportion of subjects who lost ≥ 5% of baseline body weight with semaglutide was 68.8% [22].”
§ Efficacy of GLP-1 RA Approved for Weight Management in Patients With or Without Diabetes: A Narrative Review > Results > Trial on Semaglutide in Persons with Diabetes
What the sources say
- Not checked yetcites [22] Davies M, Færch L, Jeppesen OK, et al.; STEP 2 Study Group. 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. 2021; 397:971–984. source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
In the paper
“The placebo-adjusted weight loss and adverse effect profiles were similar to those in STEP 1 for semaglutide and to SCALE Obesity and Prediabetes for liraglutide [19].”
§ Efficacy of GLP-1 RA Approved for Weight Management in Patients With or Without Diabetes: A Narrative Review > Results > Trial on Semaglutide vs. Liraglutide in Persons Without Diabetes
What the sources say
- Not checked yetcites [19] Rubino DM, Greenway FL, Khalid U, et al; STEP 8 Investigators. Effect of weekly subcutaneous semaglutide vs daily liraglutide on body weight in adults with overweight or obesity without diabetes: the STEP 8 randomized clinical trial. JAMA. 2022; 327:138–150. source
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the 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].”
§ Efficacy of GLP-1 RA Approved for Weight Management in Patients With or Without Diabetes: A Narrative Review > Discussion
What the sources say
- Not checked yetcites [15] Wilding JPH, Batterham RL, Calanna S, et al.; STEP 1 Study group. Once-weekly semaglutide in adults with overweight or obesity. N Engl J Med. 2021; 384(11):989. source
- Not checked yetcites [16] Wadden TA, Bailey TS, Billings LK, et al.; STEP 3 Investigators. 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. 2021; 325:1403–1413. source
- Not checked yetcites [17] Rubino D, Abrahamsson N, Davies M, et al.; STEP 4 Investigators. 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. 2021; 325:1414–1425. source
- Not checked yetcites [22] Davies M, Færch L, Jeppesen OK, et al.; STEP 2 Study Group. 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. 2021; 397:971–984. source
plain- Asserted: passes — The authors put it forward as true.
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- 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
“Lifestyle intervention alone is generally associated with moderate weight loss of around 5–7% that is gradually regained and yields a great proportion of poor responders [24].”
§ Efficacy of GLP-1 RA Approved for Weight Management in Patients With or Without Diabetes: A Narrative Review > Discussion
What the sources say
- Not checked yetcites [24] Acosta A, Abu Dayyeh BK, Port JD, Camilleri M. Recent advances in clinical practice challenges and opportunities in the management of obesity. Gut. 2014;63:687–95. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The baseline BMI, BMI change at 1 month, incidence of nausea and vomiting, delayed gastric emptying shortly after intervention, baseline appetite and satiety measures and some polymorphisms in GLP-1 receptor were suggested as potential predictors by some smaller studies, but the results are inconclusive [7–9].”
§ Efficacy of GLP-1 RA Approved for Weight Management in Patients With or Without Diabetes: A Narrative Review > Introduction
What the sources say
- Not checked yetcites [7] Nathan BM, Rudser KD, Abuzzahab MJ, Fox CK, Coombes BJ, Bomberg EM, Kelly AS. Predictors of weight-loss response with glucagon-like peptide-1 receptor agonist treatment among adolescents with severe obesity. Clin Obes. 2016;6:73–8. source
- Not checked yetcites [8] Jensterle M, Pirš B, Goričar K, Dolžan V, Janež A. Genetic variability in GLP-1 receptor is associated with inter-individual differences in weight lowering potential of liraglutide in obese women with PCOS: a pilot study. Eur J Clin Pharmacol. 2015;71:817–24. source
- Not checked yetcites [9] Halawi H, Khemani D, Eckert D, O’Neill J, Kadouh H, Grothe K, Clark MM, Burton DD, Vella A, Acosta A, Zinsmeister AR, Camilleri M. Effects of liraglutide on weight, satiation, and gastric functions in obesity: a randomised, placebo-controlled pilot trial. Lancet Gastroenterol Hepatol. 2017;2:890–9. source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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- 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 approval of once daily liraglutide, 3.0 mg, and once weekly semaglutide, 2.4 mg, for chronic weight management provides a novel effective strategy against obesity.”
- Also stated in: § Introduction · plain
“The first drug for weight management approved by the Food and Drug Administration (FDA) and European Medicine Agency (EMA) is GLP-1 RA liraglutide 3.0 mg with once daily administration [4].”
- Also stated in: § Introduction · plain
“The next generation GLP-1 RA semaglutide 2.4 mg is the latest anti-obesity medication, approved by the FDA in June 2021.”
§ Efficacy of GLP-1 RA Approved for Weight Management in Patients With or Without Diabetes: A Narrative Review > Abstract
What the sources say
- Not checked yetcites [4] United States Food and Drug Administration. FDA NEWS RELEASE. FDA Approves New Drug Treatment for Chronic Weight Management, First Since 2014. Avaiable at: https://www.fda.gov/news-events/press-announcements/fda-approves-new-drug-treatment-chronic-weight-management-first-2014 [6. 9. 2021].
- Not checked yetcites [5] Lau J, Bloch P, Schäffer L, et al. Discovery of the once-weekly Glucagon-Like Peptide-1 (GLP-1) analogue semaglutide. J Med Chem. 2015;155:3484–92.
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.
- Also stated in: § Introduction · plain
In the paper
“One limitation that could have impact on the inter-trial comparations is that the studies with and without diabetes were not well balanced regarding sex and race [27].”
§ Efficacy of GLP-1 RA Approved for Weight Management in Patients With or Without Diabetes: A Narrative Review > Discussion
What the sources say
- Not checked yetcites [27] Bradley CL, McMillin SM, Hwang AY, Sherrill CH. High-dose once-weekly semaglutide: a new option for obesity management. Ann Pharmacother. 2021. https://doi.org/10.1177/10600280211053867. 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.
It may state two separate claims as one.
In the paper
“Bariatric surgery is the most effective antiobesity management strategy characterized by average of 30–40% weight loss, but it comes at a cost of irreversibility, surgery-related complications and considerable percentage of late complications [2].”
§ Efficacy of GLP-1 RA Approved for Weight Management in Patients With or Without Diabetes: A Narrative Review > Discussion
What the sources say
- Not checked yetcites [2] Jepsen MM, Christensen MB. Emerging glucagon-like peptide 1 receptor agonists for the treatment of obesity. Expert Opin Emerg Drugs. 2021;26:231–43. 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
“Notably, SCALE Insulin trial explored the antiobesity efficacy of liraglutide in diabetics treated with basal insulin that has well-established weight gain potential [21].”
§ Efficacy of GLP-1 RA Approved for Weight Management in Patients With or Without Diabetes: A Narrative Review > Results > Trials on Liraglutide in Persons with Diabetes
What the sources say
- Not checked yetcites [21] Garvey WT, Birkenfeld AL, Dicker D, et al. Efficacy and safety of liraglutide 3.0 mg in individuals with overweight or obesity and type 2 diabetes treated with basal insulin: the SCALE insulin randomized controlled trial. Diabetes Care. 2020;43:1085–93. source
boosteddirect- 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
“Given that it has been previously reported that females respond to GLP-1 RAs better than men, this limitation should be taken into consideration [28].”
§ Efficacy of GLP-1 RA Approved for Weight Management in Patients With or Without Diabetes: A Narrative Review > Discussion
What the sources say
- Not checked yetcites [28] Wilding JP, Overgaard RV, Jacobsen LV, Jensen CB, le Roux CW. Exposure-response analyses of liraglutide 3.0 mg for weight management. Diabetes Obes Metab. 2016;18:491–9. source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
In the paper
“Compared with liraglutide, semaglutide has been subjected to some minor structural changes that resulted in greater efficacy and gained pharmacokinetic properties that allow once weekly dosing of semaglutide vs. once daily administration of liraglutide [5].”
§ Efficacy of GLP-1 RA Approved for Weight Management in Patients With or Without Diabetes: A Narrative Review > Introduction
What the sources say
- Not checked yetcites [5] Lau J, Bloch P, Schäffer L, et al. Discovery of the once-weekly Glucagon-Like Peptide-1 (GLP-1) analogue semaglutide. J Med Chem. 2015;155:3484–92.
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
“A recently published study performed in the real-world setting complemented the data obtained from clinical trials and reinforced the benefits of liraglutide for obese patients with type 2 diabetes, showing beneficial actions on glycaemic parameters as well as cardiometabolic risk factors in both non-obese and obese patients with type 2 diabetes, with a greater efficacy in the latter [30].”
§ Efficacy of GLP-1 RA Approved for Weight Management in Patients With or Without Diabetes: A Narrative Review > Conclusion
What the sources say
- Not checked yetcites [30] Nikolic D, Patti AM, Giglio RV, Chianetta R, Castellino G, Magán-Fernández A, Citarrella R, Papanas N, Janez A, Stoian AP, Rizvi AA, Rizzo M. Liraglutide improved cardiometabolic parameters more in obese than in non-obese patients with type 2 diabetes: a real-world 18-month prospective study. Diabetes Ther. 2022. https://doi.org/10.1007/s13300-022-01217-z. Online ahead of print. source
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
“Weight loss increased with greater exposure and appeared to level off at the highest exposures associated with GLP-1 RAs in most individuals, but did not fully plateau in men at the doses approved for weight management [29].”
§ Efficacy of GLP-1 RA Approved for Weight Management in Patients With or Without Diabetes: A Narrative Review > Discussion
What the sources say
- Not checked yetcites [29] Patel Smith Patel D, Smith A. Patient initiation and maintenance of GLP-1 RAs for treatment of obesity. Expert Rev Clin Pharmacol. 2021; 14:1193–1204. source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The authors emphasized that this has a particular clinical relevance during the current pandemic, since patients with diabetes and obesity are exposed to the most severe forms of COVID-19, related complications and death; in addition, cardiometabolic complications have increased globally in the last 2 years because of the reduced access to healthcare facilities for patients with chronic diseases,”
§ Efficacy of GLP-1 RA Approved for Weight Management in Patients With or Without Diabetes: A Narrative Review > Conclusion
What the sources say
- Not checked yetcites [31] Al Mahmeed W, Al-Rasadi K, Banerjee Y, Ceriello A, Cosentino F, Galia M, Goh SY, Kempler P, Lessan N, Papanas N, Rizvi AA, Santos RD, Stoian AP, Toth PP, Rizzo M; CArdiometabolic Panel of International experts on Syndemic COvid-19 (CAPISCO). Promoting a Syndemic Approach for Cardiometabolic Disease Management During COVID-19: The CAPISCO International Expert Panel. Front Cardiovasc Med 2021; 8:787761. 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
“STEP 1 and STEP 2 were designed to have Asians as at least 10% of the population and have a greater proportion of Asians than the other trials [23].”
§ Efficacy of GLP-1 RA Approved for Weight Management in Patients With or Without Diabetes: A Narrative Review > Discussion
What the sources say
- Not checked yetcites [23] Kushner RF, Calanna S, Davies M, et al. Semaglutide 2.4 mg for the Treatment of Obesity: Key Elements of the STEP Trials 1 to 5. Obesity (Silver Spring). 2020; 28:1050–1061. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper relies on this without support.
Weight loss of 15% or more has a disease-modifying effect in people with diabetes.
“This observation is of clinical importance since loss of 15% or more of body weight can have a disease-modifying effect in people with diabetes.”
The paper relies on this without support.
Weight loss of at least 10% to 15% leads to significant health benefits.
“Until recently, the treatment gap existed in the therapeutic strategy to achieve ≥ 10 to ≥ 15% of weight loss, which leads to significant health benefits.”
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 source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Glucagon-like peptide 1-receptor agonists (GLP-1RA)s like liraglutide, exenatide, and the most recent addition, semaglutide, are a newer class of drugs with proven efficacy in the management of obesity in the general population. 17”
From Semaglutide for the treatment of antipsychotic-associated weight gain in patients not responding to metformin – a case series (2023) · cites this paper as [17]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) are used widely for the management of obesity and type 2 diabetes [1].”
From Association between glucagon-like peptide-1 receptor agonist use and peri-operative pulmonary aspiration: a systematic review and meta-analysis (2025) · cites this paper as [1]
In the citing paper
“Due to their significant contribution to weight loss, they have been recently approved for the treatment of obesity in patients with or without T2DM [16,17].”
From GLP-1 Receptor Agonists in Non-Alcoholic Fatty Liver Disease: Current Evidence and Future Perspectives (2023) · cites this paper as [16]
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
§ Efficacy of GLP-1 RA Approved for Weight Management in Patients With or Without Diabetes: A Narrative Review > Results
“DaviesSCALE Diabetes [19]”
§ Efficacy of GLP-1 RA Approved for Weight Management in Patients With or Without Diabetes: A Narrative Review > References
“19. Rubino DM, Greenway FL, Khalid U, et al; STEP 8 Investigators. Effect of weekly subcutaneous semaglutide vs daily liraglutide on body weight in adults with overweight or obesity without diabetes: the STEP 8 randomized clinical trial.”
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
§ Efficacy of GLP-1 RA Approved for Weight Management in Patients With or Without Diabetes: A Narrative Review > Results > Trials on Semaglutide in Persons Without Diabetes
“in one small short-term, single-centre, double-blind, parallel-group short RTC investigating the effects of once-weekly subcutaneous (s.c.) semaglutide 2.4 mg on gastric emptying, appetite and energy intake in adults with obesity [20].”
§ Efficacy of GLP-1 RA Approved for Weight Management in Patients With or Without Diabetes: A Narrative Review > References
“20. Davies MJ, Bergenstal R, Bode B, et al.; NN8022–1922 Study Group. Efficacy of liraglutide for weight loss among patients with type 2 diabetes: the scale diabetes randomized clinical trial.”
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
§ Efficacy of GLP-1 RA Approved for Weight Management in Patients With or Without Diabetes: A Narrative Review > Results > Trials on Semaglutide in Persons Without Diabetes
“Semaglutide resulted in 10.3–17.4% difference in mean weight compared to placebo [15–17, 19].”
§ Efficacy of GLP-1 RA Approved for Weight Management in Patients With or Without Diabetes: A Narrative Review > Results
“− 17.4% vs. -5% from week 0 to 68− 7.9% vs. + 6.9% from week 20—68 | − 12.4%from week 0− 14.8% from week 20–68”
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
“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%).”
§ Efficacy of GLP-1 RA Approved for Weight Management in Patients With or Without Diabetes: A Narrative Review > Discussion
Reported 25.9 · recomputed 27
Citations
Cites
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
A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management
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“That may also explain some of the response differences [26].”
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MANAGEMENT OF ENDOCRINE DISEASE: Are all GLP-1 agonists equal in the treatment of type 2 diabetes?
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High-Dose Once-Weekly Semaglutide: A New Option for Obesity Management
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Metadata
- Authors
- Jensterle, M., Rizzo, M., Haluzík, M., & Janež, A.
- Affiliations
- University of Ljubljana (SI)
- University of Palermo (IT)
- Corresponding author
- Janež, Andrej
- Venue
- Advances in Therapy
- Published
- 2022-05-03
- Volume
- 39
- Issue
- 6
- Pages
- 2452-2467
- ISSN
- 0741-238X (ISSN-L)
- 1865-8652
- PMC
- PMC9063254
- OpenAlex
- W4225300035
- Cited by
- 215
- References
- 29
- Citations by year
- 2026: 39 · 2025: 66 · 2024: 62 · 2023: 39 · 2022: 9
- FWCI
- 6.32
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Advances in Therapy (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Nova Science Publishers (Nova Science Publishers, Inc.) (submittedVersion, other-oa)
- Funders
- Javna Agencija za Raziskovalno Dejavnost RS (P1-0170, P3-0298)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Pharmacology and Obesity Treatment
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- GLP-1 receptor agonists, obesity, weight management, liraglutide, semaglutide, diabetes mellitus, weight loss efficacy, lifestyle intervention, hypoglycemia, glycosuria, gut microbiota, exercise adherence
- MeSH terms
- Glucagon-Like Peptide-1 Receptor, Liraglutide, Diabetes Mellitus, Type 2, Glucagon-Like Peptides, Humans, Hypoglycemic Agents, Obesity, Weight Gain, Weight Loss, Glucagon-Like Peptide 1
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