Do GLP-1 drugs protect the heart, and what else have trials found?
In the SELECT trial, 6.5% of the semaglutide group had a major heart event versus 8% on placebo.
The best evidence so far comes from a large trial, and it points to a benefit for some people. In March 2024 the FDA expanded Wegovy's indication to reducing the risk of cardiovascular death, heart attack and stroke in adults with cardiovascular disease who are obese or overweight, based on a placebo-controlled, randomized, double-blind trial sponsored by Novo. That trial, called SELECT, randomly assigned 17,604 people with existing cardiovascular disease and overweight or obesity, but without diabetes, to semaglutide or placebo. Over a mean follow-up of 39.8 months, major adverse cardiovascular events (cardiovascular death, nonfatal heart attack or nonfatal stroke) occurred in 6.5% of the semaglutide group and 8.0% of the placebo group. The trial reported a hazard ratio of 0.80, the source of the widely quoted 20% lower risk. This lesson reports trial results; it is not medical advice.
Major cardiovascular events in the SELECT trial
% of participants
| With a major event (%) | |
|---|---|
| Semaglutide group | 6.5 % of participants |
| Placebo group | 8 % of participants |
Heart trials do not end there. In a phase III trial in people with obesity and , tirzepatide reduced a combined endpoint of urgent heart-failure visits, hospitalizations, more frequent diuretic treatment and cardiovascular death by 38% over two years compared with placebo. In December 2024 the FDA approved tirzepatide as the first medication for moderate to severe , and in August 2025 it expanded Wegovy's indication to a liver condition, MASH with moderate to advanced .
Not every hope has panned out, and that is part of the human story here. In November 2025 Novo announced results of two large studies, evoke and evoke+, which failed to slow the progression of Alzheimer's disease versus placebo. A 2022 UK study failed to find any advantage of GLP-1 agonists for Parkinson's disease.
Other ideas are early. GLP-1 agonists are under development for substance use disorder, but so far the cited evidence is from non-human animals.
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Recap
SELECT, a Novo-funded trial, found a roughly 20% lower risk of major cardiovascular events in people with heart disease and overweight or obesity, but Alzheimer's trials failed.
💡 A trick to remember it · One heart win, one liver win, one sleep win, and one Alzheimer's miss: count the trials, not the headlines.
Surprising fact · Tirzepatide was the first medication approved in December 2024 for moderate to severe obstructive sleep apnea.
Connects to
- 📈 How did diabetes drugs become weight-loss drugs, and what did the trials find?
- 🩺 What are the side effects of GLP-1 drugs, and do they cost muscle?
- 💭 What is 'food noise', and do GLP-1 drugs quiet it?
- 🫀 How does your heart pump, and what is the "lub-dub" you hear?
- 🚨 What actually happens inside the body during a heart attack?
- Semaglutide
Sources (4)
No source, no claim. Every fact in this lesson (16 claims) cites at least one of these.