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Stroke Risk Reduction in Diabetes Care
Stroke Risk Reduction and Outcomes With Novel Therapies in Diabetes Care

Released: August 26, 2024

Expiration: August 25, 2025

Alejandro A. Rabinstein
Alejandro A. Rabinstein, MD, FAHA
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Key Takeaways
  • There is a clinical association between diabetes and increased risk of both first and recurrent stroke, and the stroke risk doubles among patients with diabetes vs those without diabetes.
  • Diabetes increases stroke risk through mechanisms like atherosclerosis, small vessel disease, and cardiac embolism, and this risk is potentiated by comorbidities, such as hypertension, dyslipidemia, and obesity.
  • New guidelines recommend the use GLP-1 receptor agonist and SGLT2 inhibitors in patients with type 2 diabetes to reduce the risk of cardiovascular events, including first and recurrent stroke.

Diabetes Effect on Stroke Risk
The association between stroke and diabetes is both significant and clinically relevant at multiple levels. Patients with diabetes have approximately twice the risk of experiencing a stroke compared with those without diabetes. In addition, up to one third of patients with a history of stroke also have concomitant diabetes, and these patients are more likely to experience a stroke at a younger age. The likelihood of stroke recurrence is 50% higher in those with diabetes and a history of stroke compared with those without diabetes who have had a previous stroke.

Diabetes can increase the risk of ischemic stroke through various mechanisms, including large artery atherosclerosis, an increased prevalence of small vessel disease in the brain, and cardiac embolism through an increased risk of atrial fibrillation.

Impact of Diabetes on Stroke Outcomes
In addition to the increased risk of both first and recurrent stroke in patients with diabetes, those who experience a stroke tend to have worse outcomes post stroke. This includes higher mortality rates, worse functional outcomes in survivors, and greater cognitive performance over time post stroke.

Diabetes is associated with other metabolic and vascular risk factors, most notably obesity, hypertension, and dyslipidemia. These factors contribute to increased arterial wall stiffness, reduced vasomotor reactivity, diminished endothelial function, and activation of the inflammatory cascade, both before and during a stroke.

Pharmacological Interventions and Guidelines
Although stricter glycemic control has not been associated with a decreased risk of cardiovascular events, including stroke and other macrovascular complications, newer pharmacologic agents for type 2 diabetes are effective at reducing cardiovascular morbidity. Of note, glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) have been shown to reduce the risk of cardiovascular events and are associated with a reduction in nonfatal ischemic stroke. Overall, both GLP-1 RAs and sodium-glucose co-transporter-2 (SGLT2) inhibitors are effective in lowering the risk of cardiovascular events in general. Yet, the data for stroke reduction is more convincing for GLP-1 RAs.

All international guidelines now recommend the use of GLP-1 RAs or SGLT2 inhibitors to reduce the risk of cardiovascular events, including stroke. However, the evidence for stroke reduction is weaker for SGLT2 inhibitors. Furthermore, the American Heart Association’s secondary stroke prevention guidelines recommend adding pioglitazone—a thiazolidinedione with a different mechanism of action—for stroke prevention, as it has been shown in several randomized controlled trials to reduce the risk of stroke as well.

Finally, and of importance, the SELECT trial studied the effect of semaglutide (a GLP-1 RA) in patients with overweight or obesity and without diabetes. The trial found a reduction in the combined endpoint of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke. However, the risk reduction for nonfatal stroke did not reach statistical significance.

Overall, the key takeaway is that GLP-1 RAs can reduce the risk of cardiovascular events in both patients with diabetes and those with obesity without diabetes. Healthcare professionals, including neurologists, primary care providers, and endocrinologists, treating patients with a history of stroke, should prescribe GLP-1 RAs to patients with type 2 diabetes, regardless of glycemic control, to help reduce the risk of subsequent strokes.

Go online to learn more about GLP-1 RAs and stroke risk reduction, including a roundtable webinar where I will discuss this topic in more detail with 2 other expert faculty.

Your Thoughts?
In your clinical practice, how often are you prescribing GLP-1 RAs for patients with type 2 diabetes and a history of stroke? You can join the conversation by answering the polling question and posting a comment below.

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