Semaglutide weight loss held for four years in SELECT trial analysis

Adults with heart disease and overweight or obesity who took semaglutide lost weight for more than a year and kept most of it off for four years, according to a prespecified analysis of the SELECT trial published in Nature Medicine. At 208 weeks, mean weight was down 10.2% with semaglutide versus 1.5% with placebo ^[2].

SELECT enrolled 17,604 adults who had existing cardiovascular disease and were overweight or obese, but who did not have diabetes ^[2]. The trial previously reported that semaglutide reduced major adverse cardiovascular events by 20% compared with placebo (hazard ratio 0.80, 95% confidence interval 0.72 to 0.90; P < 0.001) ^[2]. Participants received semaglutide or placebo on top of standard-of-care recommendations for preventing a second cardiovascular event, and the trial was not focused on weight loss ^[2]. Semaglutide is a GLP-1 receptor agonist; the article notes that once-weekly subcutaneous semaglutide 2.4 mg (Wegovy) is approved for chronic weight management in the United States, and that semaglutide at doses up to 2.0 mg (Ozempic) is approved for type 2 diabetes ^[2].

In this analysis, weight loss continued for 65 weeks and was then sustained through the end of the trial at 208 weeks ^[2]. Other body measurements moved in the same direction. Waist circumference fell by a mean of 7.7 cm with semaglutide versus 1.3 cm with placebo, and waist-to-height ratio fell 6.9% versus 1.0% ^[2]. All comparisons against placebo were statistically significant (P < 0.0001) ^[2]. The article reports that clinically meaningful weight loss occurred in both sexes and across all races, body sizes and regions studied ^[2].

Serious adverse events were less common among people taking semaglutide than among those taking placebo, and that pattern held in every BMI category. Rates, expressed as events per 100 years of observation, were 43.23 versus 50.48 for BMI under 30; 43.54 versus 49.66 for BMI 30 to under 35; 51.07 versus 52.73 for BMI 35 to under 40; and 47.06 versus 60.85 for BMI 40 or higher, with semaglutide listed first ^[2]. The analysis also found that semaglutide was associated with increased rates of stopping the trial product, and that discontinuations increased as BMI class decreased ^[2]. The percentage of participants who stopped has not been reported.

Why it matters for patients

Most weight-loss medication trials run for a year or two. This analysis followed participants for four years and found that weight lost early in treatment was largely still gone at the end ^[2]. For anyone weighing whether a long-term injectable medication is worth starting or continuing, duration of effect is the main new piece of information here.

The population studied shapes how far the results travel. Everyone in SELECT had established cardiovascular disease, and none had diabetes ^[2]. Whether the same weight and waist results would appear in people without heart disease, or in people with type 2 diabetes, has not been reported in this analysis. The measurements also come from a clinical trial in which participants received standard cardiovascular care; how closely the pattern would match routine practice is not established by these data.

The tolerability finding is the other practical point. More people on semaglutide stopped taking the trial product than people on placebo, and stopping was more common among those with lower BMI ^[2]. Gastrointestinal side effects are the most common reason people discontinue GLP-1 medications, but this analysis summary does not break down why participants stopped or how the two groups differed in specific side effects. How weight behaved after participants stopped the drug is also not reported here.

The article notes that improvements in cardiovascular risk factors, blood sugar and quality-of-life measures generally begin with weight loss of about 5%, and that larger losses are linked to larger improvements ^[2]. The average 10.2% reduction seen at four years sits above that threshold, though individual results in the trial varied and averages describe groups rather than any one person.

SELECT is registered as ClinicalTrials.gov identifier NCT03574597 ^[2].

What happens next

No follow-up milestones for this analysis have been disclosed. The trial's cardiovascular results were published separately, and no additional analyses beyond the ones described here have been reported.