Summary: In a prespecified anthropometric analysis of the SELECT trial (17,604 adults with established cardiovascular disease and overweight or obesity but without diabetes), once-weekly semaglutide produced a placebo-subtracted weight reduction of 10.2% at week 208 (semaglutide -11.7% versus placebo -1.5%; P<0.0001), with sustained loss across four years. Waist circumference and waist-to-height ratio also fell more with semaglutide, and serious adverse events were fewer than with placebo.
PICO Summary
| Element | Detail |
|---|---|
| Population | 17,604 adults aged 45 years or older with preexisting cardiovascular disease and overweight (BMI 27 kg/m2 or higher) or obesity, without diabetes; double-blind, randomised, placebo-controlled multicentre trial (SELECT), 41 countries. |
| Intervention | Once-weekly subcutaneous semaglutide 2.4 mg, titrated over 16 weeks (n=8,803), followed for a mean of 208 weeks. |
| Comparison | Matching once-weekly placebo injection (n=8,801) over the same period; both arms received standard cardiovascular care. |
| Outcome | At week 208: mean weight change -11.7% with semaglutide versus -1.5% with placebo (treatment difference -10.2%; 95% CI -11.0 to -9.4; P<0.0001). Waist circumference fell -7.7 cm versus -1.3 cm and waist-to-height ratio -6.9% versus -1.0% (P<0.0001 for both). Weight loss continued to about week 65 and was sustained to four years. Serious adverse events were fewer with semaglutide across all BMI categories; trial product discontinuation was higher with semaglutide and rose as BMI class fell. No absolute risk reduction or NNT reported (this analysis addresses weight, not a binary clinical event). |
Semaglutide and long-term weight loss (SELECT)
RCT · CVD + overweight/obesity, no diabetes · 208 weeks
Once-weekly semaglutide produced a placebo-subtracted weight loss of about 10% that was reached by week 65 and sustained across four years, with parallel reductions in central adiposity.
Expert Commentary
This prespecified analysis confirms that the weight benefit of semaglutide 2.4 mg seen in shorter obesity trials is durable: a placebo-subtracted reduction of roughly 10% was reached by about 65 weeks and held across four years, the longest randomised follow-up reported for this agent in a non-diabetic population. Because SELECT was double-blinded and randomised, the comparison is internally robust, and the parallel falls in waist circumference and waist-to-height ratio are reassuring markers of central adiposity rather than lean-mass loss alone. The verdict is that semaglutide delivers clinically meaningful, sustained weight reduction in this group. The principal limitation is that weight here is a secondary, prespecified endpoint of a cardiovascular outcomes trial, not the registration objective, and the analysis was funded by the manufacturer, with several authors employed by the sponsor; the higher discontinuation rate, increasing as baseline BMI fell, also tempers the headline figures and signals real-world tolerability friction. Can I use this with my patients? Yes, for an adult with established cardiovascular disease and overweight or obesity but no diabetes, this is directly applicable and supports long-term continuation rather than short courses. Clinicians should counsel on tolerability and the likelihood of weight regain if the drug is stopped, and future work should report body-composition and cost-effectiveness data to guide who benefits most.
References
Ryan DH, Lingvay I, Deanfield J, 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
