Compared to other oral antidiabetic monotherapies, sulfonylureas were associated with the highest rates of serious hypoglycemia, according to a study published in Pharmacoepidemiology & Drug Safety.

Researchers performed a retrospective cohort study to evaluate the risks of serious hypoglycemia among adults with diabetes receiving metformin, a sulfonylurea, a meglitinide, or a thiazolidinedione as monotherapy. Specifically, Medicaid patients newly initiated on metformin, glimepiride, glipizide, glyburide, pioglitazone, rosiglitazone, nateglinide, or repaglinide from California, Florida, New York, Ohio, and Pennsylvania were included. 

Patients who were using dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 agonists, or sodium-glucose co-transporter 2 inhibitors were not included in the analysis. 

Study authors looked at the incidence of serious hypoglycemia within 180 days after treatment initiation using a diagnosis-based algorithm. They quantified incidence rates based on age and gender for each drug and calculated propensity score-adjusted hazard ratios vs. metformin using Cox proportional hazards regression. 

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The data showed glyburide had the highest standardized occurrence rate of serious hypoglycemia, followed by glimepiride, glipizide, repaglinide, nateglinide, rosiglitazone, pioglitazone, and metformin. Occurrence rates were higher for all study drugs taken at higher average daily doses. 

Compared to metformin, the adjusted hazard ratios were as follows: glyburide 3.95 (95% CI: 3.66–4.26), glimepiride 2.57 (95% CI: 2.38–2.78), glipizide 2.03 (95% CI: 1.64–2.52), repaglinide 1.21 (95% CI: 0.89–1.66), nateglinide 0.90 (95% CI: 0.75–1.07), and pioglitazone 0.80 (95% CI: 0.68–0.93).

Overall, the findings indicate the highest rate of serious hypoglycemia was seen with glyburide; a lower adjusted risk was noted with pioglitazone compared to metformin. Nateglinide and rosiglitazone exhibited similar risks to that of metformin. 

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