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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- Findingreasoning
Having diabetes is consistently associated with a smaller weight-loss response to GLP-1 receptor agonists than not having diabetes.
“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.”
Quote in the paperSubstantial claim - Also stated in: § Introduction · boosted
- Findingnone given
In participants without diabetes, high-dose liraglutide and semaglutide both met the FDA efficacy benchmark criteria.
“In summary, participants without diabetes treated with high-dose liraglutide and semaglutide reached both efficacy-benchmark criteria.”
Quote in the paperSubstantial claim - Findingcitation
The FDA efficacy benchmark criteria for weight-management products were met in the phase 2 liraglutide study, SCALE Obesity and Prediabetes, and SCALE Maintenance.
“Both critera were met in phase 2 study [14], SCALE Obesity and Predabetes [10] and SCALE Maintenance [11] trials.”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [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 in the free run.
- cites [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 in the free run.
- cites [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 in the free run.
- Findingcitation
In patients with diabetes, weight loss of at least 15% was achieved almost exclusively by those receiving liraglutide or semaglutide, not by those receiving placebo.
“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.”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [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 in the free run.
- cites [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 in the free run.
- cites [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 in the free run.
- Also stated in: § Conclusion · boosted
- Findingcitation
In people without diabetes, liraglutide 3.0 mg produces a mean weight loss 3.4% to 6.1% greater than placebo.
“Liraglutide resulted in 3.4 to 6.1% difference in mean weight loss compared to placebo [10–14, 19].”
Quote in the paperSubstantial claim0 of 6 sources checked- cites [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 in the free run.
- cites [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 in the free run.
- cites [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 in the free run.
- cites [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 in the free run.
- cites [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 in the free run.
- cites [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
Not checked in the free run.
- Findingcitation
Semaglutide leads to greater weight loss than liraglutide.
“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].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [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
Not checked in the free run.
- Also stated in: § Trial on Semaglutide vs. Liraglutide in Persons Without Diabetes · boosted
- Findingcitation
In people without diabetes, 50.5% to 73% of those treated with liraglutide lose at least 5% of baseline body weight.
“The proportion of subjects who lost ≥ 5% of baseline body weight was 50.5–73% [10–14, 19].”
Quote in the paperSubstantial claim0 of 6 sources checked- cites [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 in the free run.
- cites [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 in the free run.
- cites [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 in the free run.
- cites [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 in the free run.
- cites [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 in the free run.
- cites [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
Not checked in the free run.
- Findingcitation
In people without diabetes, 86.4% to 88.7% of those treated with semaglutide lose at least 5% of baseline body weight.
“The proportion of subjects who lost ≥ 5% of baseline body weight was 86.4–88.7% [15–17, 19].”
Quote in the paperSubstantial claim0 of 4 sources checked- cites [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 in the free run.
- cites [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 in the free run.
- cites [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 in the free run.
- cites [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
Not checked in the free run.
- Findingcitation
The FDA efficacy benchmark criteria for weight-management products were met in the STEP 1, STEP 3, STEP 4, and STEP 8 trials of semaglutide.
“Both efficacy benchmark criteria for weight management products were met in STEP 1, 3, 4 and 8 trials [15–17, 19].”
Quote in the paperSubstantial claim0 of 4 sources checked- cites [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 in the free run.
- cites [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 in the free run.
- cites [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 in the free run.
- cites [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
Not checked in the free run.
- Findingcitation
In people without diabetes, semaglutide 2.4 mg produces a mean weight loss 10.3% to 17.4% greater than placebo.
“Semaglutide resulted in 10.3–17.4% difference in mean weight compared to placebo [15–17, 19].”
Quote in the paperSubstantial claim0 of 4 sources checked- cites [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 in the free run.
- cites [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 in the free run.
- cites [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 in the free run.
- cites [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
Not checked in the free run.
- Findingcitation
No new safety signals were identified when comparing participants with diabetes to non-diabetic cohorts.
“No new safety signals were identified comparing participants with diabetes to non-diabetic cohorts [29].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [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
Not checked in the free run.
- Findingcitation
In the SCALE Insulin trial, fewer hypoglycaemic episodes were reported with liraglutide 3 mg than with placebo.
“In the SCALE Insulin trial, fewer hypoglycaemic episodes were reported with liraglutide 3 mg than with placebo.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [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 in the free run.
- Findingcitation
Rates of dehydration and renal impairment as consequences of nausea, vomiting, or diarrhoea leading to volume depletion were comparable between GLP-1 receptor agonists and placebo across the SCALE and STEP trials.
“Other adverse events of special interest were dehydration and renal impairment as consequences of nausea, vomiting or diarrhoea leading to volume depletion. The rates of these adverse events across SCALE and STEP trials were comparable between GLP-1 RAs and placebo.”
Quote in the paperSubstantial claim - Interpretationreasoning
Liraglutide 3.0 mg and semaglutide 2.4 mg, when combined with lifestyle intervention, are effective treatments for chronic weight management in adults with and without diabetes.
“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: § Key Summary Points · plain
“Liraglutide, 3.0 mg, and semaglutide, 2.4 mg, added to lifestyle intervention, provide a novel effective strategy against obesity in patients with and without diabetes.”
Quote in the paperSubstantial claim - Also stated in: § Key Summary Points · plain
- Study design and conductcitation
STEP 2 had a greater proportion of men (49.1%) than STEP 1, STEP 3, and STEP 4 (19.0% to 25.9%).
“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%).”
Quote in the paperSubstantial claim0 of 4 sources checked- cites [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 in the free run.
- cites [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 in the free run.
- cites [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 in the free run.
- cites [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 in the free run.
- Interpretationreasoning
GLP-1 receptor agonists approved for weight management can fill the treatment gap for achieving at least 10% to 15% weight loss in a substantial proportion of treated individuals.
“Until recently, the treatment gap existed in the therapeutic strategy to achieve ≥ 10 to ≥ 15% of weight loss, which leads to significant health benefits. GLP-1 RAs approved for weight management can fill this gap in a significant proportion of treated individuals.”
Quote in the paperSubstantial claim- Rests on an assumption: Weight loss of at least 10% to 15% leads to significant health benefits.
- Premisecitation
The reasons for the weaker response to GLP-1 receptor agonists in people with diabetes compared with those without diabetes are unclear.
“The underlying reasons for the weaker response for both GLP-1 RAs in people with diabetes compared to cohorts without diabetes are unclear, although there are some hypothetical explanations [1].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [1] Lancet Lingvay I, Sumithran P, Cohen RV, le Roux CW. Obesity management as a primary treatment goal for type 2 diabetes: time to reframe the conversation. Lancet. 2021 Sep 30: S0140–6736(21)01919-X.
Not checked in the free run.
- Premisecitation
No reliable models exist to predict an individual's weight-loss response to GLP-1 receptor agonists.
“The reliable models that might predict weight reducing potential at the individual level have not been identified yet.”
- Also stated in: § Introduction · plain
“there are currently almost no reliable predictive models to assess the weight reducing potential at the individual level.”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [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 in the free run.
- cites [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 in the free run.
- cites [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
Not checked in the free run.
- Also stated in: § Introduction · plain
- Interpretationreasoning
Background therapy and fear of hypoglycaemia do not explain the differential GLP-1 receptor agonist effect in patients treated with metformin or SGLT-2 inhibitors, because these drugs do not promote hypoglycaemia or weight gain.
“However, the background therapy and the fear of hypoglycaemia do not explain the differential effect of GLP-1 RA in patients treated with metformin or SGLP-2 inhibitors because these drugs do not promote hypoglycaemia or weight gain.”
Quote in the paperSubstantial claim - Interpretationnone given
Variations in race and ethnicity across the trials could affect differences in efficacy.
“The variations in the race and ethnicity of participants across the trials could also have an impact on the differences in efficacy.”
Quote in the paperNot a substantial claim - Premisecitation
Weight loss with GLP-1 receptor agonists shows substantially more interindividual variability than glycaemic control does.
“For both drugs, there is substantially more interindividual variability regarding weight loss than there is for glycaemic control [6].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [6] Nauck MA, Meier JJ. Management of endocrine disease: are all GLP-1 agonists equal in the treatment of type 2 diabetes? Eur J Endocrinol. 2019;181:R211-234. source
Not checked in the free run.
- May combine two claims. 16
- Classified as probably not a substantial claim. 2
May combine two claims.
Findingnone givenIn people with diabetes, the mean placebo-subtracted weight loss with GLP-1 receptor agonists added to lifestyle intervention is 4% to 6.2%, whereas in people without diabetes it is 6.1% to 17.4%.
“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.”
Quote in the paperSubstantial claim- Also stated in: § Conclusion · plain
May combine two claims.
FindingcitationIn patients with diabetes, semaglutide met both FDA efficacy benchmark criteria, whereas liraglutide did not meet the mean-difference criterion versus placebo.
“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].”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [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 in the free run.
- cites [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 in the free run.
- cites [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 in the free run.
May combine two claims.
FindingcitationIn the SCALE Diabetes and SCALE Insulin trials, liraglutide's mean weight-loss difference versus placebo was below 5% after one year, but 51.8% to 54.3% of liraglutide-treated participants lost at least 5% of baseline body weight.
“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].”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [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 in the free run.
- cites [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 in the free run.
May combine two claims.
FindingcitationIn the STEP 2 trial, both FDA efficacy benchmark criteria were met; semaglutide produced a mean weight loss 6.2% greater than placebo, and 68.8% of participants lost at least 5% of baseline body weight.
“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].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [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 in the free run.
May combine two claims.
FindingcitationThe placebo-adjusted weight loss and adverse effect profiles in STEP 8 were similar to those in STEP 1 for semaglutide and to SCALE Obesity and Prediabetes for liraglutide.
“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].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [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
Not checked in the free run.
May combine two claims.
FindingcitationThe percentage of Caucasian participants was 76%, 62%, 76%, and 84% in STEP 1 through STEP 4, respectively.
“The percentage of Caucasian participants in each study was 76%, 62%, 76% and 84% for the STEP 1–4 trials, respectively [15–17, 22].”
Quote in the paperSubstantial claim0 of 4 sources checked- cites [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 in the free run.
- cites [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 in the free run.
- cites [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 in the free run.
- cites [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 in the free run.
May combine two claims.
PremisecitationLifestyle intervention alone typically produces about 5% to 7% weight loss, which is gradually regained and leaves many poor responders.
“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].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [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
Not checked in the free run.
May combine two claims.
PremisecitationSmaller studies have suggested several potential predictors of weight-loss response to GLP-1 receptor agonists, including baseline BMI, early BMI change, nausea and vomiting, delayed gastric emptying, appetite and satiety measures, and GLP-1 receptor polymorphisms, but the findings are inconclusive.
“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].”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites [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 in the free run.
- cites [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 in the free run.
- cites [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
Not checked in the free run.
May combine two claims.
PremisecitationLiraglutide 3.0 mg and semaglutide 2.4 mg are approved for chronic weight management.
“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.”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [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 in the free run.
- cites [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.
Not checked in the free run.
- Also stated in: § Introduction · plain
May combine two claims.
Study design and conductcitationThe studies with and without diabetes were not well balanced regarding sex and race, which could affect inter-trial comparisons.
“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].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [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
Not checked in the free run.
May combine two claims.
PremisecitationBariatric surgery is the most effective antiobesity strategy, producing average weight loss of 30% to 40%, but it carries risks of irreversibility, surgical complications, and late complications.
“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].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [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
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationBasal insulin has well-established weight gain potential.
“Notably, SCALE Insulin trial explored the antiobesity efficacy of liraglutide in diabetics treated with basal insulin that has well-established weight gain potential [21].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [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 in the free run.
Classified as probably not a substantial claim.
PremisecitationFemales respond better to GLP-1 receptor agonists than males.
“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].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [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
Not checked in the free run.
May combine two claims.
PremisecitationSemaglutide has structural changes relative to liraglutide that increase efficacy and allow once-weekly dosing.
“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].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [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.
Not checked in the free run.
May combine two claims.
PremisecitationA real-world study found that liraglutide improved glycaemic parameters and cardiometabolic risk factors in both non-obese and obese patients with type 2 diabetes, with greater efficacy in obese patients.
“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].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [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
Not checked in the free run.
May combine two claims.
PremisecitationWeight loss increases with greater GLP-1 receptor agonist exposure and appears to level off at the highest exposures in most individuals, but does not fully plateau in men at approved weight-management doses.
“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].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [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
Not checked in the free run.
May combine two claims.
PremisecitationPatients with diabetes and obesity are at risk for the most severe forms of COVID-19, related complications, and death, and cardiometabolic complications have increased globally over the last two years because of reduced healthcare access for chronic disease patients.
“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,”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [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
Not checked in the free run.
May combine two claims.
Study design and conductcitationSTEP 1 and STEP 2 were designed to include Asians as at least 10% of the population and had a greater proportion of Asians than the other trials.
“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].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [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
Not checked in the free run.
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?
Glucagon-like peptide-1 receptor agonists have proven efficacy in the management of obesity in the general population.
“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]
The Key Summary Points and Results report effective weight management with liraglutide and semaglutide in people with and without diabetes, supporting the general efficacy claim. The citing sentence also names exenatide, but the review’s Methods and Results cover liraglutide and semaglutide, not exenatide; our copy therefore does not support that example. (LLM, conf=0.87)
Experimental — accuracy not yet measuredGlucagon-like peptide-1 receptor agonists are used widely for the management of obesity and type 2 diabetes.
“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]
GLP-1 RAs have been approved for the treatment of obesity in patients with or without T2DM.
“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.
Table 2 misnumbers its trial references
MinorTable 2 cites reference 19 for SCALE Diabetes, but reference 19 is the STEP 8 trial in people without diabetes. Its SCALE Insulin and STEP 2 rows are likewise cited as references 20 and 21, although their entries in the reference list are 21 and 22.
“DaviesSCALE Diabetes [19]”
“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.”
A semaglutide study is cited as a liraglutide diabetes trial
MinorThe cited reference 20 describes SCALE Diabetes and liraglutide, not the short semaglutide study described here. The semaglutide study appears as reference 18.
“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].”
“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.”
Baseline loss is presented as a placebo-adjusted semaglutide effect
MinorThe claimed upper treatment-placebo difference of 17.4% is the STEP 4 semaglutide group's loss from baseline. Table 1 instead gives its difference from placebo as 12.4% from week 0.
“Semaglutide resulted in 10.3–17.4% difference in mean weight compared to placebo [15–17, 19].”
“− 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”
The stated range of male participation excludes STEP 1
MinorThe text reports that 73% of STEP 1 participants were female, implying 27% were male. That exceeds the stated maximum of 25.9% male participants in the other trials.
Reported 25.9 · recomputed 27
“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%).”
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A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management
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Davies, M. J., Bergenstal, R., Bode, B., Kushner, R. F., Lewin, A., Skjøth, T. V., Andreasen, A. H., Jensen, C. B., DeFronzo, R. A., & for the NN8022-1922 Study Group (2015) · JAMA · doi:10.1001/jama.2015.9676 · Cited by 1,198 · see citing works
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on behalf of the NN8022-1923 Investigators, Wadden, T. A., Hollander, P., Klein, S., Niswender, K., Woo, V, Hale, P. M., & Aronne, L. (2013) · International Journal of Obesity · doi:10.1038/ijo.2013.120 · Cited by 842 · see citing works
on behalf of the SCALE study group, Blackman, A., Foster, G. D., Zammit, G., Rosenberg, R., Aronne, L., Wadden, T., Claudius, B., Jensen, C. B., & Mignot, E. (2016) · International Journal of Obesity · doi:10.1038/ijo.2016.52 · Cited by 583 · see citing works
Obesity management as a primary treatment goal for type 2 diabetes: time to reframe the conversation
Lingvay, I., Sumithran, P., Cohen, R. V., & le Roux, C. W. (2022) · The Lancet · doi:10.1016/s0140-6736(21)01919-x · Cited by 581 · see citing works
Healthy Weight Loss Maintenance with Exercise, Liraglutide, or Both Combined
Lundgren, J. R., Janus, C., Jensen, S. B. K., Juhl, C. R., Olsen, L. M., Christensen, R. M., Svane, M. S., Bandholm, T., Bojsen-Møller, K. N., Blond, M. B., et al. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2028198 · Cited by 536 · cited 1× · see citing works
“That may also explain some of the response differences [26].”
BackgroundFriedrichsen, M., Breitschaft, A., Tadayon, S., Wizert, A., & Skovgaard, D. (2021) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.14280 · Cited by 427 · see citing works
Semaglutide 2.4 mg for the treatment of obesity: key elements of the STEP trials 1 to 5
Kushner, R. F., Calanna, S., Davies, M., Dicker, D., Garvey, W. T., Goldman, B., Lingvay, I., Thomsen, M., Wadden, T. A., Wharton, S., et al. (2020) · Obesity · doi:10.1002/oby.22794 · Cited by 288 · see citing works
MANAGEMENT OF ENDOCRINE DISEASE: Are all GLP-1 agonists equal in the treatment of type 2 diabetes?
Nauck, M. A., & Meier, J. J. (2019) · European Journal of Endocrinology · doi:10.1530/eje-19-0566 · Cited by 254 · see citing works
Halawi, H., Khemani, D., Eckert, D., O'Neill, J., Kadouh, H., Grothe, K., Clark, M. M., Burton, D. D., Vella, A., Acosta, A., et al. (2017) · The Lancet Gastroenterology & Hepatology · doi:10.1016/s2468-1253(17)30285-6 · Cited by 224 · see citing works
Wadden, T. A., Tronieri, J. S., Sugimoto, D., Lund, M. T., Auerbach, P., Jensen, C., & Rubino, D. (2020) · Obesity · doi:10.1002/oby.22726 · Cited by 200 · see citing works
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Exposure-response analyses of liraglutide 3.0 mg for weight management
Wilding, J. P. H., Overgaard, R. V., Jacobsen, L. V., Jensen, C. B., & le Roux, C. W. (2016) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.12639 · Cited by 102 · see citing works
Emerging glucagon-like peptide 1 receptor agonists for the treatment of obesity
Jepsen, M. M., & Christensen, M. B. (2021) · Expert Opinion on Emerging Drugs · doi:10.1080/14728214.2021.1947240 · Cited by 96 · see citing works
Recent advances in clinical practice challenges and opportunities in the management of obesity
Acosta, A., Abu Dayyeh, B. K., Port, J. D., & Camilleri, M. (2014) · Gut · doi:10.1136/gutjnl-2013-306235 · Cited by 91 · see citing works
Jensterle, M., Pirš, B., Goričar, K., Dolžan, V., & Janež, A. (2015) · European Journal of Clinical Pharmacology · doi:10.1007/s00228-015-1868-1 · Cited by 86 · see citing works
Self-citationAl Mahmeed, W., Al-Rasadi, K., Banerjee, Y., Ceriello, A., Cosentino, F., Galia, M., Goh, S.-Y., Kempler, P., Lessan, N., Papanas, N., et al. (2021) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2021.787761 · Cited by 48 · see citing works
Self-citationMedication use for the treatment of diabetes in obese individuals
Wilding, J. P. H. (2017) · Diabetologia · doi:10.1007/s00125-017-4288-1 · Cited by 43 · see citing works
Nathan, B. M., Rudser, K. D., Abuzzahab, M. J., Fox, C. K., Coombes, B. J., Bomberg, E. M., & Kelly, A. S. (2016) · Clinical Obesity · doi:10.1111/cob.12128 · Cited by 39 · see citing works
Nikolic, D., Patti, A. M., Giglio, R. V., Chianetta, R., Castellino, G., Magán-Fernández, A., Citarrella, R., Papanas, N., Janez, A., Stoian, A. P., et al. (2022) · Diabetes Therapy · doi:10.1007/s13300-022-01217-z · Cited by 38 · see citing works
Self-citationPatient initiation and maintenance of GLP-1 RAs for treatment of obesity
Patel, D., & Smith, A. (2021) · Expert Review of Clinical Pharmacology · doi:10.1080/17512433.2021.1947796 · Cited by 16 · see citing works
High-Dose Once-Weekly Semaglutide: A New Option for Obesity Management
Bradley, C. L., McMillin, S. M., Hwang, A. Y., & Sherrill, C. H. (2022) · Annals of Pharmacotherapy · doi:10.1177/10600280211053867 · Cited by 16 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Marx, N., Husain, M., Lehrke, M., Verma, S., & Sattar, N. A. (2022) · Circulation · doi:10.1161/circulationaha.122.059595 · Cited by 500 · see citing works
Nevola, R., Epifani, R., Imbriani, S., Tortorella, G., Aprea, C., Galiero, R., Rinaldi, L., Marfella, R., & Sasso, F. C. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24021703 · Cited by 286 · see citing works
Glucagon-Like Peptide-1 Receptor Agonist Use and Residual Gastric Content Before Anesthesia
Sen, S., Potnuru, P. P., Hernandez, N., Goehl, C., Praestholm, C., Sridhar, S., & Nwokolo, O. O. (2024) · JAMA Surgery · doi:10.1001/jamasurg.2024.0111 · Cited by 202 · see citing works
Martins, F. F., Marinho, T. D. S., Cardoso, L. E. M., Barbosa‐da‐Silva, S., Souza‐Mello, V., Águila, M. B., & Mandarim‐de‐Lacerda, C. A. (2022) · Cell Biochemistry and Function · doi:10.1002/cbf.3751 · Cited by 115 · see citing works
SGLT2i and GLP-1 RA therapy in type 1 diabetes and reno-vascular outcomes: a real-world study
Anson, M., Zhao, S. S., Austin, P. J., Hernández, G., Malik, R. A., & Alam, U. (2023) · Diabetologia · doi:10.1007/s00125-023-05975-8 · Cited by 103 · see citing works
Muzurović, E. M., Volčanšek, Š., Zibar, K., Janež, A., Mikhailidis, D. P., Rizzo, M., & Mantzoros, C. S. (2022) · Journal of Cardiovascular Pharmacology and Therapeutics · doi:10.1177/10742484221146371 · Cited by 99 · see citing works
Self-citationObesity: pathophysiology and therapeutic interventions
Kong, Y., Yang, H., Nie, R., Zhang, X., Zuo, F., Zhang, H., & Nian, X. (2025) · Molecular Biomedicine · doi:10.1186/s43556-025-00264-9 · Cited by 89 · see citing works
Prasad, F., De, R., Korann, V., Chintoh, A. F., Remington, G., Ebdrup, B. H., Siskind, D., Knop, F. K., Vilsbøll, T., Fink-Jensen, A., et al. (2023) · Therapeutic Advances in Psychopharmacology · doi:10.1177/20451253231165169 · Cited by 88 · see citing works
“17 28 Across these trials, semaglutide demonstrated significant body weight reductions from baseline to end of treatment versus all comparators.”
BackgroundGLP-1 agonists for weight loss: pharmacology and clinical implications.
Moore, P. W., Malone, K., VanValkenburg, D., Rando, L. L., Williams, B. C., Matejowsky, H. G., Ahmadzadeh, S., Shekoohi, S., Cornett, E. M., & Kaye, A. D. (2023) · Advances in Therapy · doi:10.1007/s12325-022-02394-w · Cited by 86 · see citing works
Aldhaleei, W. A., Abegaz, T. M., & Bhagavathula, A. S. (2024) · Pharmaceuticals · doi:10.3390/ph17020199 · Cited by 80 · see citing works
Obesity accelerates cardiovascular ageing
Ruperez, C., Madeo, F., de Cabo, R., Kroemer, G., & Abdellatif, M. (2025) · European Heart Journal · doi:10.1093/eurheartj/ehaf216 · Cited by 73 · see citing works
One-Year Weight Reduction With Semaglutide or Liraglutide in Clinical Practice
Gasoyan, H., Pfoh, E. R., Schulte, R., Le, P., Butsch, W. S., & Rothberg, M. B. (2024) · JAMA Network Open · doi:10.1001/jamanetworkopen.2024.33326 · Cited by 71 · see citing works
Milder, D. A., Milder, T. Y., Liang, S. S., & Kam, P. C. A. (2024) · Anaesthesia · doi:10.1111/anae.16306 · Cited by 62 · see citing works
Alkabbani, W., Suissa, K., Gu, K. D., Cromer, S. J., Paik, J. M., Bykov, K., Hobai, I., Thompson, C. C., Wexler, D. J., & Patorno, E. (2024) · BMJ · doi:10.1136/bmj-2024-080340 · Cited by 60 · see citing works
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“4 mg is a once-weekly glucagon-like peptide-1 (GLP-1) receptor agonist (RA) that was approved for chronic weight management in June 2021.(3) The phase 3 STEP 1 trial showed that, in”
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- 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 › 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
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.
Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-04.
Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-04.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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