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Basal insulin, sulfonylureas increase risk for CV events

Insured, adult patients with type 2 diabetes that received sulfonylureas or basal insulin as a second-line antidiabetic medication therapy were at increased risk for certain CV events, according to findings recently published in JAMA Network Open.

“There is a lack of consensus about choosing subsequent [antidiabetic medications] among patients who do not achieve adequate glycemic control with metformin or do not tolerate it,” Matthew J. O’Brien, MD, MSc, of the division of general internal medicine and geriatrics, at Northwestern University Feinberg School of Medicine, and colleagues wrote.

“Comparing cardiovascular outcomes of second-line antidiabetic medications during this early transition in diabetes pharmacotherapy may help improve treatment decisions after metformin or in place of it,” they added.

Researchers investigated occurrence of stroke, ischemic heart disease, peripheral artery disease or heart failure in 132,737 insured adult patients with type 2 diabetes who had received GLP-1 receptor agonists, DPP-4 inhibitors, thiazolidinediones, SGLT2 inhibitors, sulfonylureas and basal insulin as a second-line treatment. The majority of patients were aged 45 to 64 years, men, and white.

O’Brien and colleagues found that 3,480 incident CV events occurred during 169,384 person-years of follow-up. The comparative risk for a CV event was higher after receiving basal insulin (HR = 2.03; 95% CI, 1.81-2.27) or sulfonylureas (HR = 1.36; 95% CI, 1.23-1.49) compared with a DPP-4 inhibitor.

“Collectively, these findings raise concerns about the cardiovascular safety of sulfonylureas and basal insulin compared with newer antidiabetic medications and suggest that short-term cardiovascular outcomes of newer antidiabetic medication classes may be similar among patients starting second-line treatment,” O’Brien and colleagues wrote.

“Although our findings should be interpreted with some caution due to the observational design of this study, they were robust to several rigorous sensitivity analyses and are supported by prior mechanistic and clinical evidence. Future research should compare antidiabetic medication classes on glycemic effectiveness and additional metabolic end points,” they added. – by Janel Miller

Disclosures: O’Brien reports receiving personal fees from Novo Nordisk outside the submitted work. Please see the study for all other authors' relevant financial disclosures.