Beyond weight: SELECT, SUSTAIN-6 and FLOW, the outcome trials behind the semaglutide labels

Three of the indications on the semaglutide labels have nothing to do with the number on a scale or an A1c. Each comes from one large trial that counted events: heart attacks, strokes, deaths, kidney failure. This page reports those trials the way the labels rely on them.

SUSTAIN-6: the first cardiovascular signal (Ozempic)

Published 2016, before Ozempic's approval. 3,297 adults with type 2 diabetes, 83% with established cardiovascular disease, chronic kidney disease or both, randomised to semaglutide 0.5 or 1 mg weekly or placebo. The primary outcome (cardiovascular death, non-fatal heart attack or non-fatal stroke) occurred in 6.6% on semaglutide and 8.9% on placebo, hazard ratio 0.74 (95% CI 0.58 to 0.95). Non-fatal stroke drove much of it: 1.6% versus 2.7%, hazard ratio 0.61 (95% CI 0.38 to 0.99). Cardiovascular death was similar between groups.

The trial was designed to show non-inferiority and reported superiority as a secondary observation, which is why the cardiovascular indication for Ozempic waited until January 16, 2020 (Drugs@FDA supplement 3). The retinopathy finding, hazard ratio 1.76 (95% CI 1.11 to 2.78), went straight into the label as a warning (PubMed 27633186).

SELECT: cardiovascular outcomes without diabetes (Wegovy)

The largest semaglutide trial. 17,604 adults aged 45 or older with established cardiovascular disease and a BMI of 27 or higher, without diabetes, randomised to semaglutide 2.4 mg weekly or placebo and followed for a mean of 39.8 months. The primary outcome occurred in 6.5% on semaglutide versus 8.0% on placebo, hazard ratio 0.80 (95% CI 0.72 to 0.90). Adverse events leading to permanent discontinuation were 16.6% versus 8.2% (PubMed 37952131).

FDA added the indication on March 8, 2024 (Drugs@FDA supplement 11): to reduce major adverse cardiovascular events in adults with established cardiovascular disease and obesity or overweight. The label's maintenance dose for it is 2.4 mg recommended or 1.7 mg. The same indication was carried over to the Wegovy tablet at its December 22, 2025 approval.

Two ways to say the same result: a 20% relative reduction, or 1.5 fewer events per 100 people treated for about three years and four months. Both are true. The second is the one to hold onto when someone quotes the first.

FLOW: kidney outcomes (Ozempic)

3,533 adults with type 2 diabetes and chronic kidney disease, randomised to semaglutide 1 mg weekly or placebo, stopped early on the recommendation of a prespecified interim analysis after a median 3.4 years. The primary composite (kidney failure, a sustained 50% or greater fall in eGFR, or death from kidney or cardiovascular causes) was 24% lower on semaglutide: 331 versus 410 first events, hazard ratio 0.76 (95% CI 0.66 to 0.88). Kidney-specific components: hazard ratio 0.79 (95% CI 0.66 to 0.94). Cardiovascular death: 0.71 (95% CI 0.56 to 0.89). Major cardiovascular events: 0.82 (95% CI 0.68 to 0.98). Death from any cause: 0.80 (95% CI 0.67 to 0.95). The annual eGFR decline was slower by 1.16 mL/min/1.73 m². Serious adverse events were less frequent on semaglutide, 49.6% versus 53.8% (PubMed 38785209).

FDA added the indication on January 28, 2025 (Drugs@FDA supplement 25): to reduce the risk of sustained eGFR decline, end-stage kidney disease and cardiovascular death in adults with type 2 diabetes and chronic kidney disease, at 1 mg weekly after 4 weeks at 0.5 mg.

What these trials share, and what they do not

All three were placebo-controlled, event-driven and funded by Novo Nordisk. All three enrolled people at high baseline risk, which is where absolute benefits are largest and where the indications are written. None enrolled people at low cardiovascular risk, none tested compounded semaglutide, and none tested a dose other than the one on the label for that indication. Ozempic's cardiovascular and kidney indications rest on 0.5 to 1 mg; Wegovy's rests on 2.4 mg (or 1.7 mg).

The Ozempic and Wegovy dosing guides show how each indication maps to a dose. The FormBlends Research site digests SELECT, FLOW and SUSTAIN-6 alongside the tirzepatide outcome trials, and The Science explains the mechanisms the trials are thought to reflect.