Highest risk seen with glipizide versus other sulfonylureas and DPP4 inhibitors as second-line therapy<\/p>\n<\/h3>\n
By Elana Gotkine HealthDay Reporter<\/b>
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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<\/em>.<\/p>\n 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.<\/p>\n 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.<\/p>\n “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.”<\/p>\n Several authors disclosed ties to the biopharmaceutical industry.<\/p>\n