Efficacy of GLP-1 RA Approved for Weight Management in Patients With or Without Diabetes: A Narrative Review

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.