GLP-1 Medicines and Stroke: What SUSTAIN-6, REWIND and the Meta-Analyses Show About Stroke Risk

Do GLP-1 medicines lower stroke risk? In people with type 2 diabetes, yes: across the large cardiovascular outcome trials, GLP-1 receptor agonists cut strokes by roughly 15% compared with placebo. The drop comes from ischemic strokes, the kind caused by a blocked artery. Hemorrhagic strokes and deaths from stroke have not clearly fallen, and the case for people without diabetes is still unproven.

Stroke is common enough that a modest relative reduction matters. The CDC counts more than 795,000 strokes a year in the United States, about one every 40 seconds, and about 87% of them are ischemic. Obesity, diabetes and high blood pressure are among the leading causes, which is exactly the territory GLP-1 medicines were built for.

This article walks through the stroke results from SUSTAIN-6 and REWIND, what three meta-analyses found when they pooled the trials, what SELECT and SOUL add, where tirzepatide stands, and what has never been tested at low doses.

Did semaglutide lower stroke risk in SUSTAIN-6?

Marso and colleagues, New England Journal of Medicine, 2016

Yes. SUSTAIN-6 was the first trial to show a clear stroke signal for a GLP-1 medicine. It randomized 3297 people with type 2 diabetes to weekly injectable semaglutide, 0.5 mg or 1.0 mg, or placebo for 104 weeks. Most were high risk: 83.0% already had cardiovascular disease, chronic kidney disease or both.

Nonfatal stroke occurred in 1.6% of the semaglutide group and 2.7% of the placebo group, a hazard ratio of 0.61. The confidence interval ran from 0.38 to 0.99, so the result only just cleared the line for statistical significance. Nonfatal heart attacks also fell, but that difference could have been chance.

SUSTAIN-6 also flagged a safety issue. Complications of diabetic retinopathy were more common on semaglutide (hazard ratio 1.76), which matters for anyone who already has diabetic eye disease. Our article on GLP-1 medicines and eye health covers that signal.

Which kinds of stroke did dulaglutide prevent in REWIND?

Gerstein and colleagues, Lancet Diabetes & Endocrinology, 2020

Dulaglutide prevented ischemic strokes but not hemorrhagic ones. REWIND randomized 9901 adults aged 50 or older with type 2 diabetes to weekly dulaglutide 1.5 mg or placebo and followed them for a median 5.4 years. Participants had type 2 diabetes plus additional cardiovascular risk factors, not necessarily established heart disease.

A stroke occurred in 158 people on dulaglutide (3.2%) and 205 on placebo (4.1%), a hazard ratio of 0.76. Ischemic stroke fell to a similar degree (hazard ratio 0.75), and disabling strokes were also less common (hazard ratio 0.74). Hemorrhagic stroke did not change (hazard ratio 1.05).

One detail is easy to miss. When a stroke did happen, it was no less severe on dulaglutide than on placebo. The drug appeared to lower the chance of a stroke, not to soften one once it started. The authors called this an exploratory analysis, so it supports the pooled findings rather than standing as proof by itself.

What do the meta-analyses show about GLP-1 medicines and stroke?

International Journal of Stroke, 2024; European Stroke Journal, 2024

Pooled trial data put the stroke reduction at about 15%. The largest stroke-specific analysis, published in the International Journal of Stroke in 2024, combined 11 cardiovascular outcome trials with 82,140 participants, 34.6% of them women, and 247,596 person-years of follow-up. Stroke was less common on GLP-1 medicines (risk ratio 0.85), and so was nonfatal stroke (risk ratio 0.87). The result held for daily and weekly drugs and for oral and injected forms.

The number needed to treat was 200: in these trials, about 200 people had to take a GLP-1 medicine to prevent one stroke. That is a population-level figure from high-risk groups, most of them living with type 2 diabetes and existing heart or kidney disease.

A second 2024 analysis in the European Stroke Journal, covering 13 trials and 65,878 people with type 2 diabetes, broke the result down by stroke type. GLP-1 medicines cut ischemic stroke (odds ratio 0.74) but not hemorrhagic stroke (0.92), and fatal stroke did not fall significantly (0.80). That matches what REWIND found in a single trial.

Do GLP-1 medicines reduce deaths from stroke?

International Journal of Cardiology Heart & Vasculature, 2025

Not clearly. A 2025 meta-analysis that added the SELECT and FLOW trials pooled 11 randomized trials and 85,373 patients with a mean age of 63.5. It found a 15% lower risk of any stroke (odds ratio 0.85) and a 13% lower risk of nonfatal stroke (odds ratio 0.87), but fatal stroke was essentially unchanged (odds ratio 0.94).

Fatal strokes are a small slice of all strokes in these trials, so even pooled data may be too thin to settle the question. The fair reading is that GLP-1 medicines reduce how often strokes happen in people with diabetes, and that an effect on stroke deaths has not been shown.

Does semaglutide lower stroke risk in people without diabetes?

SELECT, New England Journal of Medicine, 2023; Stroke, 2026

A stroke benefit has not been shown on its own in people without diabetes. SELECT enrolled 17,604 adults aged 45 or older with established cardiovascular disease and a BMI of 27 or more, none with diabetes, and gave them semaglutide 2.4 mg weekly or placebo. Over a mean 39.8 months, the combined outcome of cardiovascular death, heart attack or stroke occurred in 6.5% on semaglutide against 8.0% on placebo (hazard ratio 0.80).

That combined result is real, but it does not tell you which part of it moved. A 2026 review in the journal Stroke, covering 35 studies (31 in animals, 4 in people), concluded that recent randomized trials have not shown a significant effect on stroke incidence or recovery in patients without diabetes. The same review found GLP-1 drugs reduced the size of brain damage in animal stroke models, a promising lead that has not yet carried over to people.

SELECT also showed the cost of tolerability: 16.6% on semaglutide stopped the drug for adverse events against 8.2% on placebo. Our overview of GLP-1 medicines and cardiovascular health covers the heart side of these trials.

Do oral semaglutide and tirzepatide show the same stroke benefit?

SOUL, New England Journal of Medicine, 2025; European Stroke Journal, 2024

Oral semaglutide lowered combined cardiovascular events, and the stroke meta-analysis found no difference between oral and injected GLP-1 medicines. SOUL randomized 9650 people with type 2 diabetes and heart or kidney disease to oral semaglutide, up to 14 mg daily, or placebo. Over a median 49.5 months, the combined outcome occurred in 12.0% against 13.8% (hazard ratio 0.86). The SOUL abstract did not break out stroke on its own.

Tirzepatide has less stroke-specific evidence. The European Stroke Journal analysis included 4 tirzepatide trials and found no difference in overall cardiovascular benefit between GLP-1 medicines and the dual GIP/GLP-1 drug. The authors were explicit, though, that dedicated trials are needed before anyone can say tirzepatide prevents strokes.

Why would a GLP-1 medicine lower stroke risk?

Risk factors, arteries and the animal data

The likeliest explanation is that GLP-1 medicines act on several stroke risk factors at once. They lower blood sugar, body weight and, in many people, blood pressure, and the CDC lists high blood pressure among the leading causes of stroke. Because the benefit shows up in ischemic strokes and not hemorrhagic ones, researchers suspect a slower build-up of artery disease plays a part. Our article on GLP-1 medicines and blood pressure covers the pressure data.

In animal stroke models, GLP-1 drugs reduced infarct size, and researchers have proposed lower oxidative stress and inflammation as reasons. Those findings come from animals and have not been confirmed as a protective effect in people. Atrial fibrillation is another stroke route, and the evidence there is covered in our article on GLP-1 medicines and atrial fibrillation.

Has a GLP-1 microdose been tested for stroke prevention?

What the evidence can and cannot support

No. Every trial behind the stroke findings used standard doses: semaglutide 0.5 mg or 1.0 mg weekly in SUSTAIN-6, dulaglutide 1.5 mg in REWIND, semaglutide 2.4 mg in SELECT and oral semaglutide up to 14 mg daily in SOUL. SUSTAIN-6 reported its two doses together, so even the lower of them was not tested on its own for stroke.

Stroke trials also need thousands of people and years of follow-up because strokes are uncommon events. Nothing comparable exists for low-dose regimens, so any claim that a microdose protects the brain goes beyond the evidence. For someone worried about stroke, the treatments with direct proof, such as blood pressure control, cholesterol-lowering therapy and anticoagulation for atrial fibrillation, remain the foundation, decided with a clinician.

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