GLP‑1 and heart health: the cardiovascular benefits explained

Introduction

Some GLP‑1 medicines have proven cardiovascular benefits, but the evidence and approved uses differ by product. In SELECT, weekly semaglutide 2.4 mg reduced the relative risk of major cardiovascular events by 20% compared with placebo in adults with established cardiovascular disease and overweight or obesity, without diabetes. Tirzepatide also has completed cardiovascular trial results, discussed below. [1]

The SELECT trial: what it found

Published in the New England Journal of Medicine in 2023, SELECT enrolled 17,604 adults aged 45 or older with a BMI of at least 27, established cardiovascular disease, and no history of diabetes. Participants received semaglutide 2.4 mg or placebo by weekly injection, with average follow-up of about 40 months. [1]

The primary outcome combined cardiovascular death, nonfatal heart attack, and nonfatal stroke, known as major adverse cardiovascular events (MACE). It occurred in 6.5% of the semaglutide group and 8.0% of the placebo group. The hazard ratio was 0.80 (95% confidence interval 0.72 to 0.90), reported as a 20% relative risk reduction. The observed event rates differed by 1.5 percentage points; this was not a 20-percentage-point reduction. [1]

How GLP‑1 medicines may support heart health

Researchers are studying several overlapping pathways. The clinical benefits are better established than the contribution of each proposed mechanism:

• Weight reduction: Losing excess weight may reduce cardiovascular strain and improve several risk factors. It does not fully explain the observed cardiovascular benefit.
• Reduced inflammation: Some GLP‑1 medicines lower inflammatory markers such as C-reactive protein. This may contribute to effects against atherosclerosis, the buildup of plaque in arteries.
• Metabolic changes: Blood pressure and some blood-fat measurements may improve, all of which contribute to a healthier cardiovascular profile. Do not assume every medicine produces the same change in HDL cholesterol.
• Vascular and heart-tissue effects: Laboratory and animal studies suggest effects on blood vessels and heart tissue. Direct protection of human heart muscle remains incompletely defined. [2]

SELECT enrolled people without diabetes. In a separate analysis, researchers found that semaglutide reduced cardiovascular events regardless of participants’ starting HbA1c, a measure of average blood sugar, or changes in HbA1c during treatment. That does not establish identical protection from every GLP‑1 medicine or for every patient. [11]

Wegovy’s cardiovascular approval

In March 2024, the FDA approved Wegovy injection to reduce cardiovascular death, heart attack, and stroke risk in adults with established cardiovascular disease and either overweight or obesity. It was the first weight-management medicine approved for this purpose. [3] The FDA has approved Wegovy tablets for the same use. [4]

An approved indication is specific to the medicine and patient population. For example, Ozempic also has a cardiovascular indication for adults with type 2 diabetes and established cardiovascular disease. Ask your clinician which indication applies to your situation. [5]

What studies show about stopping treatment

A 2026 BMJ Medicine study used U.S. Veterans Affairs records to examine people with type 2 diabetes who continued, discontinued, or interrupted GLP‑1 receptor agonist treatment. It studied the medication class, not only semaglutide. Compared with continued use, stopping for one year was associated with a 14% higher relative risk of major cardiovascular events over the study’s three-year follow-up. [6]

This was an observational analysis designed to emulate a trial, not a randomized trial of stopping treatment. It cannot prove that stopping caused the difference or establish the same risk for people without diabetes. [6]

Separately, the STEP 1 extension found that participants regained about two-thirds of their prior weight loss in the year after semaglutide and structured lifestyle support were withdrawn, with several cardiometabolic measures moving back toward baseline. Discuss a stopping or switching plan with your prescriber, including alternatives if cost or side effects make treatment difficult. [7]

Tirzepatide and cardiovascular outcomes

SURPASS-CVOT is complete, with results published in 2025. It compared tirzepatide with dulaglutide, a medicine with established cardiovascular benefits, in people with type 2 diabetes and atherosclerotic cardiovascular disease. [8]

The primary cardiovascular outcome occurred in 12.2% of participants taking tirzepatide and 13.1% taking dulaglutide (hazard ratio 0.92; 95.3% confidence interval 0.83 to 1.01). Tirzepatide met the trial’s noninferiority criterion: its results stayed within a prespecified margin of dulaglutide’s. Because the upper end of the confidence interval was above 1.0, the trial did not show that tirzepatide worked better than dulaglutide for the primary cardiovascular outcome. The trial compared two active medicines and had no placebo or semaglutide group. [8]

In August 2026, the FDA approved Mounjaro to reduce the risk of major cardiovascular events in adults with type 2 diabetes who are at high risk for those events. Zepbound contains the same medicine, tirzepatide, but the FDA has approved it for weight reduction and obstructive sleep apnea, with no cardiovascular indication. [9] [10]

Share your progress with Shotsy

Shotsy lets you record doses and weight trends and export a PDF summary for appointments. Use the record to discuss treatment with your care team; it cannot measure cardiovascular protection or establish eligibility for insurance coverage.

Conclusion

SELECT and SURPASS-CVOT provide evidence for specific medicines in specific populations. Review the benefits, side effects, and long-term plan with your prescriber. If you need to stop or switch treatment, ask how your cardiovascular and diabetes care should be managed.