Comparative safety of sulfonylureas among U.S. nursing home residents

Abstract

Background: The comparative safety of sulfonylureas (SUs) in nursing home (NH) residents remains understudied despite widespread use. We compared the effects of three SU medications and initial SU doses on adverse glycemic and cardiovascular events among NH residents.

Methods: This national retrospective cohort study linked Medicare claims with Minimum Data Set 2.0 assessments for long-stay NH residents aged ≥65 years between January 2008 and September 2010. Exposures were the SU medication initiated (glimepiride, glipizide, or glyburide) and doses (standard or reduced). One-year outcomes were hospitalizations or emergency department visits for severe hypoglycemia, heart failure (HF), stroke, and acute myocardial infarction (AMI). After the inverse probability of treatment and inverse probability of censoring by death weighting, we estimated hazard ratios (HR) using Cox regression models with robust 95% confidence intervals (CI).

Results: The cohort (N = 6821) included 3698 new glipizide, 1754 glimepiride, and 1369 glyburide users. Overall, the mean (standard deviation) age was 81.4 (8.2) years, 4816 (70.6%) were female, and 5164 (75.7%) were White non-Hispanic residents. The rates of severe hypoglycemia were 30.3 (95% CI 22.3-40.1), 49.0 (95% CI 34.5-67.5), and 35.9 (95% CI 22.2-54.9) events per 1000 person-years among new glipizide, glimepiride, and glyburide users, respectively (glimepiride versus glipizide HR 1.6, 95% CI 1.0-2.4, p = 0.04; glyburide versus glipizide HR 1.2, 95% CI 0.7-1.9, p = 0.59). The rates of severe hypoglycemia were 27.1 (95% CI 18.6-38.0) and 42.8 (95% CI 33.6-53.8) events per 1000 person-years among new users of reduced and standard SU doses, respectively (HR 2.2, 95% CI 1.4-3.5, p < 0.01). Rates of HF, stroke, and AMI were similar between medications and doses.

Conclusions: Among long-stay NH residents, new use of glimepiride and standard SU doses resulted in higher rates of severe hypoglycemic events. Cardiovascular outcomes may not be affected by the choice of SU medication or dose.

Keywords: diabetes mellitus; frailty; nursing homes; sulfonylurea compounds.

Figure 1.. Comparative Safety of New Glipizide, Glimepiride, and Glyburide Use among Nursing Home Residents.

Presents hazard ratios with robust 95% confidence intervals before and after inverse probably of treatment and censoring weighting based on 203 covariates (see Supplementary Table S4). New use of glipizide was the reference group. Abbreviations: AMI, acute myocardial infarction; HF, heart failure; HR, hazard ratio; IPW, inverse probably of treatment and censoring weighting.

Figure 2.. Comparative Safety of Initial Standard versus Reduced Sulfonylurea Dose among Nursing Home Residents.

Presents hazard ratios with robust 95% confidence intervals before and after inverse probably of treatment and censoring weighting based on 203 covariates (see Supplementary Table S5). Initial reduced dose was the reference group. Abbreviations: AMI, acute myocardial infarction; HF, heart failure; HR, hazard ratio; IPW, inverse probably of treatment and censoring weighting.