SELECT trial: semaglutide 2.4 mg cuts major cardiovascular events by 20%

Novo Nordisk announced on August 8, 2023 that semaglutide 2.4 mg — the dose sold as Wegovy — reduced the risk of major adverse cardiovascular events by 20% in adults with overweight or obesity in the SELECT trial ^[1]. It was the first time a medicine approved for weight management showed a reduction in heart attacks, strokes and cardiovascular death in a dedicated outcomes trial.

What the company reported

The headline result was a 20% reduction in major adverse cardiovascular events with semaglutide 2.4 mg compared with placebo in adults with overweight or obesity ^[1]. In the language later used on the Wegovy label, "major adverse cardiovascular events" means the combination of cardiovascular death, non-fatal myocardial infarction (heart attack), and non-fatal stroke ^[1].

That combined endpoint matters because it is the standard yardstick regulators use to judge whether a drug protects the heart, rather than just improving a number on a lab report or a scale.

The August 8 announcement was a topline summary, not the full dataset. Detailed results — including how many people were enrolled, how long they were followed, the absolute number of events in each group, and the safety findings — were not part of this initial release ^[1]. Those specifics are not yet known from this announcement alone.

What this dose is

Semaglutide 2.4 mg is delivered by once-weekly injection under the brand name Wegovy ^[1]. Wegovy injection pens deliver doses of 0.25 mg, 0.5 mg, 1 mg, 1.7 mg and 2.4 mg ^[1]. Semaglutide is a GLP-1 receptor agonist that works in obesity by lowering calorie intake through GLP-1 receptors in areas of the brain that regulate appetite ^[1].

The drug's label carries a boxed warning for an increased risk of thyroid C-cell tumors ^[1]. Warnings and precautions include acute pancreatitis, acute gallbladder disease, low blood sugar, acute kidney injury, hypersensitivity reactions, diabetic retinopathy complications in people with type 2 diabetes, increased heart rate, and suicidal behavior and ideation ^[1]. The most common side effects, occurring in at least 5% of people, include nausea, diarrhea, vomiting, constipation, abdominal pain, headache and fatigue ^[1].

Why it matters for patients

Until this result, the case for taking a weight-loss drug rested mainly on weight change and on related measures such as blood pressure or blood sugar. A trial showing fewer heart attacks, strokes and cardiovascular deaths puts semaglutide in a different category — one where the benefit is measured in events people care about avoiding.

That distinction has practical weight with insurers and with the FDA, because a cardiovascular outcomes result can support a separate approved indication rather than a cosmetic or lifestyle framing. On March 8, 2024, Wegovy was approved in the US to reduce cardiovascular risk in people with overweight or obesity and established cardiovascular disease ^[1]. The current label states the injection is indicated, along with a reduced-calorie diet and increased physical activity, to reduce the risk of cardiovascular death, non-fatal heart attack or non-fatal stroke in adults with established cardiovascular disease and either obesity or overweight ^[1].

Whether any individual insurer covers the drug on that basis is not addressed in the available source. Neither is the size of the benefit for people without established heart disease — SELECT enrolled adults who already had cardiovascular disease ^[1].

What happens next

Full SELECT results were presented on November 11, 2023 at the American Heart Association Scientific Sessions and published at the same time in the New England Journal of Medicine ^[1]. The FDA added the cardiovascular risk reduction indication on March 8, 2024 ^[1]. A later analysis, reported May 13, 2025, found that the reduction in cardiovascular events appeared early — before clinically meaningful changes in body weight ^[1].