Glipizide Linked to Highest MACE-4 Risk in Individuals With Type 2 Diabetes

MONDAY, July 28, 2025 (HealthDay News) — For individuals with type 2 diabetes (T2D) and moderate cardiovascular risk treated with metformin, the risk for major adverse cardiovascular events is highest for glipizide as a second-line therapy compared with other sulfonylureas and dipeptidyl peptidase 4 inhibitors (DPP4is), according to a study published online July 24 in JAMA Network Open.

Alexander Turchin, M.D., from Brigham and Women”s Hospital in Boston, and colleagues conducted a comparative effectiveness research study involving individuals with T2D and moderate cardiovascular risk treated with metformin monotherapy. A total of 48,165 individuals were eligible, of whom 18,147 started glipizide; 14,282 started glimepiride; 1,887 started glyburide; and 13,849 started a DPP4i as a second-line therapy.

The researchers found that during a median follow-up of 37 months, 3,158 individuals (6.6 percent) experienced a 4-point composite of major adverse cardiovascular events (MACE-4; myocardial infarction, ischemic stroke, heart failure hospitalization, or cardiovascular death from any of these conditions). The estimated five-year risks for MACE-4 were 8.1, 8.4, 8.6, and 9.1 percent for DPP4is, glyburide, glimepiride, and glipizide, respectively. The five-year risk ratios (95 percent confidence intervals) of MACE-4 were 1.13 (1.03 to 1.23), 1.07 (0.96 to 1.16), and 1.04 (0.83 to 1.24) for glipizide, glimepiride, and glyburide, respectively, compared with DPP4is.

“While sulfonylureas are popular and affordable diabetes medications, there is a lack of long-term clinical data on how they affect cardiac health in comparison to more neutral alternatives like dipeptidyl peptidase 4 inhibitors,” Turchin said in a statement. “Our study underscores the importance of evaluating each drug in a particular pharmacological class on its own merits.”

Several authors disclosed ties to the biopharmaceutical industry.

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