GLP-1 Drugs Outperform Metformin in Cutting Diabetes and Death Risk for High-Risk Adults

Adults living with prediabetes and obesity who take GLP-1 medications face significantly lower risks of developing type 2 diabetes and dying from any cause compared to those prescribed metformin, according to a massive new observational study.

Researchers tracked electronic health records for 256,492 adults with prediabetes and obesity, whose average age was 52. Over a three-year follow-up period, patients taking GLP-1 drugs—including semaglutide, tirzepatide, liraglutide, and dulaglutide—showed a 31% lower risk of developing type 2 diabetes and a 41% lower risk of death from any cause compared to those taking metformin. The GLP-1 group also experienced 20% fewer strokes, 15% fewer heart attacks, and 25% fewer cases of heart failure.

The preliminary findings are scheduled for presentation at the American Heart Association’s Scientific Sessions 2026 in Chicago. The data hasn’t yet gone through the full peer-review process.

Targeting Prediabetes Early

Metformin has long served as the standard first-line oral medication to manage blood sugar, often paired with lifestyle changes or prescribed off-label to delay diabetes onset. However, researchers suggest the newer class of injectable weight-loss and diabetes drugs could shift how doctors approach early metabolic care.

“The 41% lower risk of death from any cause surprised me most,” said Dr. Vinicius de Sousa Barzon Serra, a research fellow in cardiovascular medicine at the Mayo Clinic in Scottsdale, Arizona, and lead author of the study. “Most earlier research on these medications focused on people who already had diabetes. Our study suggests the prediabetes stage may be an important time to consider them, rather than waiting until they develop type 2 diabetes.”

According to American Heart Association statistics, nearly 40% of U.S. Adults have prediabetes, a state where blood sugar levels are elevated but remain below the diagnostic threshold for type 2 diabetes. Up to 10% of people with prediabetes progress to full type 2 diabetes every single year.

Study Constraints and Clinical Context

Despite the dramatic numbers, the study relies on observational data, meaning it demonstrates an association rather than direct cause and effect. Researchers noted that electronic records can contain missing or inaccurate data, and unmeasured variables like exact drug dosage or patient compliance could have skewed the results. Plus, the analysis grouped all GLP-1 medications together, preventing a head-to-head comparison between specific drugs.

Dr. Bradley Serwer, an interventional cardiologist and chief medical officer at VitalSolution who wasn’t involved in the research, noted that while traditional preventive care focuses on blood pressure, cholesterol, and smoking cessation, doctors should also aggressively target metabolic dysfunction.

However, medical experts stress that patients shouldn’t make sudden medication changes. Metformin remains a low-cost, safe option with decades of real-world evidence, while lifestyle habits like diet, exercise, and weight management stay essential. Doctors recommend that patients evaluate GLP-1 therapies individually based on their specific cardiovascular risk factors, insurance coverage, and overall health profile.