Abstract
INTRODUCTION: Impaired renal function is a major complication of type 2 diabetes mellitus (T2DM). Mild renal impairment is present in 38% of patients with T2DM and may impact choice of antihyperglycemic agent. Sulfonylureas and dipeptidyl peptidase-4 (DPP-4) inhibitors are commonly used to treat hyperglycemia in patients with T2DM and renal impairment. Although in general sulfonylurea use is associated with an increased risk of hypoglycemia and weight gain, while DPP-4 inhibitor use is associated with a low risk of hypoglycemia, and is weight neutral, the relative efficacy and tolerability of these agents in patients with mild renal impairment has not been evaluated. METHODS: In a post hoc analysis, data from 1,211 subjects with T2DM and mild renal impairment (estimated glomerular filtration rates of 60 to <90 mL/min/1.73 m(2)), who completed 25 or 30 weeks of one of three double-blind clinical trials comparing the DPP-4 inhibitor sitagliptin 100 mg/day with sulfonylureas in titrated doses, were pooled. The analysis compared change from baseline in glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), body weight, incidence of symptomatic hypoglycemia and the percentages of subjects meeting a composite endpoint of HbA1c decrease >0.5% without symptomatic hypoglycemia or body weight gain between sitagliptin and sulfonylurea treatment groups. RESULTS: HbA1c and FPG decreased similarly with sitagliptin or sulfonylurea. A lower incidence of hypoglycemia was observed with sitagliptin. Body weight decreased with sitagliptin but increased with sulfonylurea. A greater percentage of subjects treated with sitagliptin (41.1%) than treated with sulfonylurea (16.9%) achieved the composite endpoint of >0.5% HbA1c reduction with no symptomatic hypoglycemia or body weight gain. CONCLUSION: In this analysis of subjects with T2DM and mild renal impairment, treatment with sitagliptin provided glycemic efficacy similar to sulfonylurea, with less hypoglycemia and with body weight loss compared to body weight gain seen with sulfonylurea. TRIAL REGISTRATIONS: ClinicalTrials.gov #NCT00482079, #NCT00094770, #NCT00701090.