Semaglutide and cardiovascular outcomes in adults with overweight or obesity and established cardiovascular disease without diabetes

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APA 7

Lindholm, A., Okonkwo, C., Varga, M., & Reyes-Ortiz, J. (2026). Semaglutide and cardiovascular outcomes in adults with overweight or obesity and established cardiovascular disease without diabetes. The Lancet.

MLA 9

Lindholm, A., et al. “Semaglutide and cardiovascular outcomes in adults with overweight or obesity and established cardiovascular disease without diabetes.” The Lancet, 2026.

Chicago

Lindholm, A., C. Okonkwo, M. Varga, and J. Reyes-Ortiz. 2026. “Semaglutide and cardiovascular outcomes in adults with overweight or obesity and established cardiovascular disease without diabetes.” The Lancet.

Harvard

Lindholm, A. et al. (2026) ‘Semaglutide and cardiovascular outcomes in adults with overweight or obesity and established cardiovascular disease without diabetes’, The Lancet.

Vancouver

Lindholm A, Okonkwo C, Varga M, Reyes-Ortiz J. Semaglutide and cardiovascular outcomes in adults with overweight or obesity and established cardiovascular disease without diabetes. The Lancet. 2026.

BibTeX

@article{lindholm2026semaglutide,
  title = {{Semaglutide and cardiovascular outcomes in adults with overweight or obesity and established cardiovascular disease without diabetes}},
  author = {Lindholm, A. and Okonkwo, C. and Varga, M. and Reyes-Ortiz, J.},
  year = {2026},
  journal = {The Lancet}
}

RIS

TY  - JOUR
TI  - Semaglutide and cardiovascular outcomes in adults with overweight or obesity and established cardiovascular disease without diabetes
AU  - Lindholm, A.
AU  - Okonkwo, C.
AU  - Varga, M.
AU  - Reyes-Ortiz, J.
PY  - 2026
JO  - The Lancet
ER  -

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Cardiology

Semaglutide and cardiovascular outcomes in adults with overweight or obesity and established cardiovascular disease without diabetes

Lindholm A, Okonkwo C, Varga M, Reyes-Ortiz J

ReadSearch

The Lancet

2026

Overview

A weight-loss drug that also protects the heart

Semaglutide is widely used for diabetes and obesity. Whether it also prevents heart attacks and strokes in people without diabetes has been an open question for cardiologists.

This trial randomised adults with overweight or obesity and established cardiovascular disease, none with diabetes, to weekly semaglutide or placebo, and followed them for major cardiovascular events.

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The Lancet · 2026

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The problem

The gap it addresses

Most cardiovascular outcome trials of GLP-1 drugs enrolled people with type 2 diabetes. For the much larger group with overweight or obesity and established heart disease but no diabetes, the evidence was indirect.

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The Lancet · 2026

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The idea

A placebo-controlled outcomes trial

Lowering weight and inflammation with semaglutide will reduce cardiovascular events even without diabetes.

Earlier diabetes trials showed fewer events than glucose lowering alone would explain, which pointed to effects beyond blood sugar: on weight, blood pressure and inflammation.

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The Lancet · 2026

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The method

Randomised, double-blind, event-driven

Neither participants nor investigators knew who received the drug, and the trial ran until a pre-set number of primary events had accrued, so its size was fixed by events rather than by time.

Adults aged 45 or over with a BMI of 27 or more and prior heart attack, stroke or peripheral artery disease were enrolled.

They were randomised one to one to weekly semaglutide 2.4 mg or placebo, on top of standard care.

The primary outcome was the first of cardiovascular death, heart attack or stroke.

Follow-up continued until enough events had occurred, a mean of 3.3 years.

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The Lancet · 2026

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What they found

The results

20%

Fewer major events

Relative reduction in the primary composite outcome versus placebo.

−9.4%

Weight change

Mean change in body weight with semaglutide, against −0.9% with placebo.

3.3 yrs

Follow-up

Mean time participants were followed.

16.6%

Stopped for side effects

Mostly gastrointestinal, against 8.2% on placebo.

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The Lancet · 2026

6 / 11

What they found

How the groups compared

6.5%

8.0%

Semaglutide

Placebo

Share with a major event, %

Major cardiovascular events occurred in 6.5% of the semaglutide group and 8.0% of the placebo group. The benefit appeared early, before most of the weight loss, which suggests effects beyond weight alone. More people stopped the drug because of side effects.

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The Lancet · 2026

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Use cases

Where it could be used

Secondary prevention

An added option for patients with heart disease and obesity who do not have diabetes.

Guideline updates

Evidence that cardiology and obesity guidelines can weigh when recommending GLP-1 drugs.

Shared decisions

Concrete numbers to discuss benefits against side effects and cost with patients.

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The Lancet · 2026

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In your field

For a cardiologist, this moves semaglutide from a weight drug to a prevention option.

1 in 67

Patients treated over about three years for one fewer major event, from the absolute difference of 1.5 points.

Who might qualify

Patients like those in the trial: established disease, a BMI of 27 or more, no diabetes.

What to watch

Gastrointestinal side effects drove most discontinuations, so follow-up in the first months matters.

Open questions

Whether the benefit holds at lower doses, and how it compares with other risk-lowering drugs.

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The Lancet · 2026

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Next steps

What to do with it

Read the methods and supplement

Check the population, the adjudication of events and the subgroup results.

Compare with the diabetes trials

Set this result beside the earlier GLP-1 outcome trials to see what is new.

Check the guideline response

Look for how cardiology societies have incorporated it.

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The Lancet · 2026

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Read the full paper

Semaglutide and cardiovascular outcomes in adults with overweight or obesity and established cardiovascular disease without diabetes

The Lancet · 2026

ReadSearch

The Lancet

2026