GLP-1 Use Tied to Lower Diabetes, CV Risk vs Metformin in Prediabetes

Adults with prediabetes and obesity who took glucagon-like peptide-1 receptor agonists (GLP-1 RAs) were more likely to return to normal blood glucose levels and less likely to develop type 2 diabetes, die, or have a heart attack or stroke than those who took metformin, according to preliminary research to be presented at the American Heart Association (AHA) Scientific Sessions 2026.¹

The retrospective analysis of 256,492 adults is among the largest to compare GLP-1 RAs with metformin, which, along with lifestyle modification, remains the first-line medication for prediabetes. Most prior GLP-1 research has focused on people who already have type 2 diabetes, according to study author Vinicius de Sousa Barzon Serra, MD, a research fellow in the department of cardiovascular medicine at Mayo Clinic in Scottsdale, Arizona. This study looked instead at the earlier prediabetes stage.

Nearly 40% of US adults have prediabetes, and up to 10% of them progress to type 2 diabetes each year, the AHA noted, citing its 2026 Heart Disease and Stroke Statistics and National Institutes of Health data.

“The great news with prediabetes is that it’s still possible to reverse the progression of the disease,” said Serra in a statement. “This research may add to the case for considering GLP-1 medications earlier for certain patients, rather than waiting until they develop Type 2 diabetes.”

GLP-1 Users 1.5 Times More Likely to Reach Normal Blood Glucose

Researchers drew electronic health records from the TriNetX global multicenter network, which included 104 institutions from 2010 to 2023. Patients had an average age of 52 years, 76% were women, and follow-up averaged roughly 3 years. About half were taking a GLP-1-based medication (semaglutide, tirzepatide, liraglutide, or dulaglutide), and the other half were taking metformin. The investigators matched patients on age, comorbidities such as high blood pressure, sleep apnea, and nicotine dependence, and other medications.

Compared with metformin users, GLP-1 users had a 1.5 times higher chance of reverting to normal blood glucose levels, a 31% lower risk of developing type 2 diabetes, and a 41% lower risk of death from any cause.

About 20% Fewer Strokes, 25% Fewer Heart Failure Cases

GLP-1 use was also associated with 15% fewer heart attacks, 20% fewer strokes, 25% fewer cases of heart failure, and 8% fewer cases of atrial fibrillation compared with metformin.

“The main effect these findings could have is on the shared decision-making discussion between doctors and patients exploring various treatment options and the pros and cons for each,” said Serra. “Metformin is still a first-line treatment choice. It is safe, inexpensive, and has a long track record. This is less about replacing one medication with another and more about discussing additional options with specific patients.”

Robert Eckel, MD, FAHA, a past volunteer president of the AHA and professor of medicine emeritus at the University of Colorado Anschutz Medical Campus, who was not involved in the study, said the results were not surprising and likely reflect weight loss, which is known to help prevent type 2 diabetes.

“Preventing the progression from prediabetes to type 2 diabetes keeps patients from having type 2 diabetes, and it also helps prevent heart attack and strokes,” he said in a statement. “GLP-1s provide another option for prevention, perhaps as an add-on therapy. However, costs and access to these medications are important factors.”

Trial Data Support Normoglycemia Signal, but Findings Remain Preliminary

The results echo randomized data on reversion to normoglycemia. In the phase 3 STEP 10 trial, published in 2024 in The Lancet Diabetes & Endocrinology, 81% of adults with obesity and prediabetes who received once-weekly semaglutide 2.4 mg reverted to normoglycemia at 52 weeks vs 14% of those who received placebo.² That trial compared semaglutide with placebo, not metformin.

The new analysis is observational and cannot establish cause and effect.¹ Patients and outcomes were identified through diagnosis codes, which can be incomplete; prescription records did not capture adherence or dose; and GLP-1–based agents were grouped together, so differences between individual drugs were not assessed.

References

1. GLP-1 meds linked to lower diabetes, heart risks than standard diabetes prevention med. News release. American Heart Association. November 2, 2026. Accessed November 2, 2026. https://newsroom.heart.org/news/glp-1-meds-linked-to-lower-diabetes-heart-risks-than-standard-diabetes-prevention-med
2. McGowan BM, Bruun JM, Capehorn M, et al. Efficacy and safety of once-weekly semaglutide 2·4 mg versus placebo in people with obesity and prediabetes (STEP 10): a randomised, double-blind, placebo-controlled, multicentre phase 3 trial. Lancet Diabetes Endocrinol. 2024;12(9):631-642. doi:10.1016/S2213-8587(24)00182-7