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Comparative Study
. 2018 Jan;27(1):9-18.
doi: 10.1002/pds.4337. Epub 2017 Nov 6.

Comparative risk of serious hypoglycemia with oral antidiabetic monotherapy: A retrospective cohort study

Charles E Leonard  1   2 , Xu Han  1   2 , Colleen M Brensinger  1   2 , Warren B Bilker  1   2   3 , Serena Cardillo  2   4 , James H Flory  2   5   6 , Sean Hennessy  1   2   7
Affiliations
Comparative Study

Comparative risk of serious hypoglycemia with oral antidiabetic monotherapy: A retrospective cohort study

Charles E Leonard et al. Pharmacoepidemiol Drug Saf. 2018 Jan.

Abstract

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.

Keywords: hypoglycemia; meglitinide; metformin; pharmacoepidemiology; sulfonylurea compounds; thiazolidinedione.

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Conflict of interest statement

Conflicts of interest: Dr. Leonard, Dr. Han, Dr. Bilker, Dr. Cardillo, Dr. Flory, and Ms. Brensinger have no conflicts of interest to disclose. Dr. Hennessy has received salary support through his employer for research funded by Bristol-Myers Squibb, directs a pharmacoepidemiology training program that receives support from Pfizer Inc and Sanofi US, and has consulted for GlaxoSmithKline, Merck Sharp & Dohme Corp, Novo Nordisk Pharmaceuticals Inc, and Sanofi US, all unrelated to this research.

Figures

Figure 1
Figure 1
Propensity score-adjusted hazard ratios for serious hypoglycemia, using metformin as the referent
See this image and copyright information in PMC

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