Glucagon-like peptide-1 receptor agonists (GLP-1RAs) such as semaglutide improve glycemic control and are associated with weight reduction and cardiovascular benefit in people with type 2 diabetes mellitus (T2DM). However, whether the magnitude of weight loss influences major adverse cardiovascular event (MACE) risk during semaglutide treatment remains uncertain.

A post hoc analysis of the SUSTAIN-6 trial published in Diabetes Therapy evaluated the relationship between semaglutide-associated weight loss at 56 weeks and subsequent MACE risk in people with T2DM. The analysis included 1,479 participants assigned to semaglutide in the randomized, double-blind, placebo-controlled cardiovascular outcomes trial. Participants were categorized according to percentage body weight change from baseline to week 56: no loss or weight gain, less than 5% loss, 5%-10% loss, and greater than 10% loss.

Point estimates of MACE incidence did not differ significantly across weight loss categories (P = 0.73). MACE event rates were 1.05% among participants with no weight loss or weight gain, 1.69% in those with less than 5% weight loss, 1.06% in those with 5%-10% weight loss, and 0.89% in those with greater than 10% weight loss. After adjustment for age and sex, no category of weight loss was associated with lower odds of MACE compared with the no loss/gain group.

The analysis did not identify an association between the magnitude of semaglutide-associated weight loss at 56 weeks and subsequent MACE risk in people with T2DM.