The question
Semaglutide, sold for weight loss as Wegovy and for diabetes as Ozempic, reliably helps people lose weight and lowers several risk markers.[2] But losing weight and lowering a cholesterol number are not the same as avoiding a heart attack. The clinically important question is whether the drug actually prevents the events people fear, cardiovascular death, heart attack, and stroke, in people who do not have diabetes. Until this trial, that had not been tested directly.
What they did
The SELECT trial enrolled 17,604 adults aged 45 or older who had a body-mass index of at least 27, a history of cardiovascular disease such as a prior heart attack or stroke, and no diabetes.[1] Participants were randomly assigned to a weekly injection of semaglutide at the 2.4 mg dose or a matching placebo, on top of their usual care. The trial was double-blind, meaning neither patients nor their doctors knew who got the drug, and it ran until enough events had accrued to answer the question, a mean of about 39.8 months of follow-up.[1] The primary outcome was a composite of death from cardiovascular causes, nonfatal heart attack, or nonfatal stroke.
What they found
A primary cardiovascular event occurred in 569 of 8,803 people on semaglutide (6.5%) compared with 701 of 8,801 on placebo (8.0%).[1] That works out to a hazard ratio of 0.80 (95% confidence interval 0.72 to 0.90; P<0.001), or roughly a 20% lower relative risk. In plain terms, the drug prevented about 1.5 events per 100 people over three and a half years. The benefit showed up across the components of the outcome and was not explained by weight loss alone, since the curves began separating earlier than weight change would predict. The cost side is also concrete: 16.6% of the semaglutide group stopped the drug because of side effects, mostly gastrointestinal, versus 8.2% on placebo.[1]
Why it matters
This is the first randomized evidence that a GLP-1 drug lowers hard cardiovascular outcomes in people with obesity but without diabetes, a very large group that previously had no obesity medication proven to prevent heart events. It reframes semaglutide from a weight or cosmetic drug toward a cardiovascular one, and it strengthens the case that treating obesity itself, not just its downstream complications, can change outcomes. For clinicians deciding whom to treat, it offers an evidence-based reason beyond the number on the scale.
What this does not prove
The trial enrolled a specific population, middle-aged and older adults who already had cardiovascular disease, so the results do not automatically extend to younger or lower-risk people taking the drug purely for weight loss. It cannot say whether the same benefit would appear in someone with no prior heart disease. The absolute benefit is modest; most participants in both groups did not have an event, and about 67 people would need treatment for about three years to prevent one. The trial was funded and run by the manufacturer, Novo Nordisk,[1] which does not invalidate the result but is worth noting. It also does not tell us about very long-term safety, effects after stopping the drug, or cost-effectiveness, and it cannot cleanly separate how much of the benefit comes from weight loss versus other actions of the drug.
What happens next
Follow-up analyses are examining kidney outcomes, weight regain after stopping, and which patients benefit most. Independent replication in different populations and health systems, and head-to-head comparisons with other GLP-1 drugs, will sharpen the picture. The open practical questions are less about whether the drug works and more about who should get it, for how long, and at what cost to health systems, given that the benefit, while real, is gradual and the drug is expensive and taken indefinitely.
References
- Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. New England Journal of Medicine. 2023. doi:10.1056/NEJMoa2307563
- Wilding JPH, Batterham RL, Calanna S, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. New England Journal of Medicine. 2021. doi:10.1056/NEJMoa2032183
