Summary: In a prespecified analysis of the SELECT trial (17,604 adults with established cardiovascular disease and overweight or obesity but without diabetes), semaglutide 2.4 mg weekly produced a mean weight reduction of 10.2% versus 1.5% with placebo at 208 weeks, with weight loss sustained over four years and fewer serious adverse events but more treatment discontinuations on semaglutide.
PICO Summary
| Element | Detail |
|---|---|
| Population | 17,604 adults with preexisting cardiovascular disease and overweight or obesity, without diabetes; prespecified analysis of the double-blind, placebo-controlled SELECT randomised trial (multinational, multicentre). |
| Intervention | Subcutaneous semaglutide 2.4 mg once weekly, with treatment and follow-up to 208 weeks (about 4 years). |
| Comparison | Matching placebo once weekly over the same period, on a background of standard cardiovascular care. |
| Outcome | At 208 weeks, mean weight change was -10.2% with semaglutide versus -1.5% with placebo. Waist circumference fell by -7.7 cm versus -1.3 cm, and waist-to-height ratio by -6.9% versus -1.0% (P<0.0001 for all comparisons). Serious adverse event rates were lower with semaglutide across every BMI category, but trial product discontinuation was more frequent with semaglutide and increased as baseline BMI class fell. The analysis reported descriptive between-group differences; no 95% confidence intervals, absolute risk reduction or number needed to treat were provided for these anthropometric outcomes. |
SELECT: long-term weight loss with semaglutide
RCT (prespecified analysis) · CVD + obesity, no diabetes · 208 weeks
In adults with cardiovascular disease and obesity but no diabetes, semaglutide 2.4 mg weekly cut body weight by 10.2% versus 1.5% with placebo, sustained over four years. Reported descriptively without confidence intervals.
Expert Commentary
This prespecified analysis of SELECT is reassuring on durability: a mean weight reduction of about 10% was reached by roughly 65 weeks and held for four years, the longest controlled weight-loss follow-up reported for this agent. Because randomisation was preserved and the trial was double-blind and placebo-controlled, the headline weight, waist circumference and waist-to-height comparisons are credible, and the consistent benefit across sexes, races and BMI strata strengthens generalisability. Several cautions temper the message. The trial was funded by the manufacturer, with sponsor employees among the authors, so independent confirmation of the magnitude of effect is desirable. The single most important limitation is that this is a secondary analysis of anthropometric endpoints, reported descriptively without confidence intervals or numbers needed to treat, so the precision of the between-group differences cannot be judged from the data shown. Discontinuation rose as baseline BMI fell, which matters when extrapolating to leaner patients. Can I use this with my patients? Yes, for the SELECT-type patient, an adult with established cardiovascular disease and obesity but no diabetes, this supports semaglutide as a durable adjunct to lifestyle measures, while monitoring tolerability and the higher discontinuation seen at lower BMI. Clinicians should set expectations around sustained adherence and counsel on likely weight regain if treatment stops.
References
Ryan DH, Lingvay I, Deanfield J, Kahn SE, Barros E, Burguera B, et al. Long-term weight loss effects of semaglutide in obesity without diabetes in the SELECT trial. Nat Med. 2024;30(7):2049-2057. doi:10.1038/s41591-024-02996-7