Predictors of Peak Body Weight Loss With Semaglutide in the SELECT Trial

OBJECTIVE To evaluate whether clinically available baseline characteristics predict peak percentage body weight loss (%BWL) achieved with chronic use of semaglutide. RESEARCH DESIGN AND METHODS SELECT (Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity Trial) evaluated the cardiovascular benefits of semaglutide in adults (mean age 62, 72% men) with obesity and preexisting atherosclerotic disease without diabetes. This prespecified analysis evaluated participants randomized to semaglutide who continued treatment for a minimum of 1 year. Baseline demographics, medical history, laboratory variables, and clinical measurements were candidate predictors of peak %BWL evaluated in a general linear model estimated with ordinary least squares. RESULTS Among the 7,594 SELECT participants continuously treated with semaglutide for ≥1 year (representing 86.3% of those randomized to semaglutide), median peak %BWL was 12.5% (interquartile range [IQR] 7.9–17.9), achieved after a median of 19 months (IQR 10–30) of treatment. The full model predicted <10% of the variability in peak %BWL; female sex accounted for 85.3% of this model (explaining ≈8% of the variability). Semaglutide dose was associated with peak %BWL (median 6.0% [IQR 1.9–10.9] vs. 13.3% [IQR 9.0–18.4] for those with a maximum dose of 0.24 mg vs. 2.4 mg). The highest median peak %BWL was achieved by women (16.6% [IQR 10.9–23.4]) versus men (12.4% [IQR 8.4–16.9]). CONCLUSIONS The peak amount of weight loss expected following initiation of semaglutide cannot be predicted based on clinically available baseline characteristics; unmeasured biological, behavioral, or genetic differences are likely responsible for variability in individual response. Women treated with the highest dose of semaglutide experienced the largest %BWL.