Serious Hypoglycemia Risk Compared Among Oral SU and Repaglinide Antidiabetics in T2DM
Sulfonylureas were associated with the highest rates
 
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.
 
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.
 
ABSTRACTS
Purpose
To examine and compare risks of serious hypoglycemia among antidiabetic monotherapy-treated adults receiving metformin, a sulfonylurea, a meglitinide, or a thiazolidinedione.
 
Methods
We performed a retrospective cohort study of apparently new users of monotherapy with metformin, glimepiride, glipizide, glyburide, pioglitazone, rosiglitazone, nateglinide, or repaglinide within a dataset of Medicaid beneficiaries from California, Florida, New York, Ohio, and Pennsylvania. We did not include users of dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 agonists, or sodium-glucose co-transporter 2 inhibitors. We identified serious hypoglycemia outcomes within 180 days following new use using a validated, diagnosis-based algorithm. We calculated age- and sex-standardized outcome occurrence rates for each drug and generated propensity score–adjusted hazard ratios vs metformin using Cox proportional hazards regression.
 
Results
The ranking of standardized occurrence rates of serious hypoglycemia was glyburide > glimepiride > glipizide > repaglinide > nateglinide > rosiglitazone > pioglitazone > metformin. Rates were increased for all study drugs at higher average daily doses. Adjusted hazard ratios (95% confidence intervals) vs metformin were 3.95 (3.66-4.26) for glyburide, 3.28 (2.98-3.62) for glimepiride, 2.57 (2.38-2.78) for glipizide, 2.03 (1.64-2.52) for repaglinide, 1.21 (0.89-1.66) for nateglinide, 0.90 (0.75-1.07) for rosiglitazone, and 0.80 (0.68-0.93) for pioglitazone.
 
Conclusions
Sulfonylureas were associated with the highest rates of serious hypoglycemia. Among all study drugs, the highest rate was seen with glyburide. Pioglitazone was associated with a lower adjusted hazard for serious hypoglycemia vs metformin, while rosiglitazone and nateglinide had hazards similar to that of metformin.
 
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