Four years of semaglutide: what SELECT tells us about maintenance

The short answer

In a large trial of people with established cardiovascular disease, average weight loss with semaglutide was sustained for up to four years. The result is useful for a question the first few months cannot answer: does a lower weight last over the follow-up?

A different kind of study

SELECT enrolled 17,604 adults aged 45 or older with overweight or obesity and existing cardiovascular disease, without diabetes. Participants were randomly assigned weekly semaglutide or placebo. Its main purpose was to study cardiovascular events; this paper reports a planned analysis of weight outcomes.

That distinction matters. Participants were older on average than those in many weight-loss trials, and 72.3% were men. They received standard cardiovascular care and healthy-lifestyle counseling, rather than a program specifically designed around losing weight.

The four-year result

At 208 weeks, estimated average weight change was −10.2% with semaglutide and −1.5% with placebo. Waist circumference decreased by an average of 7.7 cm versus 1.3 cm.

Weight loss with semaglutide continued for roughly 65 weeks and was then maintained. A plateau at a lower weight can represent maintenance; it does not mean people should expect the scale to keep falling indefinitely.

These are estimates for the randomized groups, including people who stopped treatment. Missing measurements were handled statistically. They are not a promise that every person completed four years of uninterrupted treatment or achieved the average result.

Why not compare this number directly with STEP 1?

STEP 1 studied a different population and included structured weight-loss support. In SELECT, investigators could slow escalation, pause treatment or use a lower dose for tolerability. The smaller average reduction does not, by itself, show that the medicine became less effective.

It is a reminder to compare the people, support and analysis behind a percentage—not just the headline number.

The trade-offs and boundaries

Treatment discontinuation was more common with semaglutide, even though serious adverse events were less common overall. Those are different measures: tolerating a medicine and experiencing a serious medical event are not the same question.

SELECT does not establish the same outcome in younger people without cardiovascular disease. This analysis also did not measure fat or lean mass directly. Its strongest contribution here is evidence about sustained average weight reduction in the population actually studied.