A Safety Comparison of Metformin vs Sulfonylurea Initiation in Patients With Type 2 Diabetes and Chronic Kidney Disease: A Retrospective Cohort Study

Abstract

Objective: To compare the safety of metformin vs sulfonylureas in patients with type 2 diabetes by chronic kidney disease (CKD) stage.

Patients and methods: This retrospective cohort study included adults in Manitoba, Canada, with type 2 diabetes, an incident monotherapy prescription for metformin or a sulfonylurea, and a serum creatinine measurement from April 1, 2006, to March 31, 2017. Patients were stratified by estimated glomerular filtration rate (eGFR) into the following groups: eGFR of 90 or greater, 60 to 89, 45 to 59, 30 to 44, or less than 30 mL/min/1.73 m². Outcomes included all-cause mortality, cardiovascular events, and major hypoglycemic episodes. Baseline characteristics were used to calculate propensity scores and perform inverse probability of treatment weights analysis, and eGFR group was examined as an effect modifier for each outcome.

Results: The cohort consisted of 21,996 individuals (19,990 metformin users and 2006 sulfonylurea users). Metformin use was associated with lower risk for all-cause mortality (hazard ratio [HR], 0.48; 95% CI, 0.40-0.58; P<.001), cardiovascular events (HR, 0.67; 95% CI, 0.52-0.86; P=.002), and major hypoglycemic episodes (HR, 0.14; 95% CI, 0.09-0.20; P<.001) when compared with sulfonylureas. CKD was a significant effect modifier for all-cause mortality (P=.002), but not for cardiovascular events or major hypoglycemic episodes.

Conclusion: Sulfonylurea monotherapy is associated with higher risk for all-cause mortality, major hypoglycemic episodes, and cardiovascular events compared with metformin. Although the presence of CKD attenuated the mortality benefit, metformin may be a safer alternative to sulfonylureas in patients with CKD.