Aim: To evaluate the efficacy and safety of saxagliptin vs. placebo in patients with type 2 diabetes mellitus (T2DM) and renal impairment.
Methods: In this multicentre, randomized, parallel-group, double-blind, placebo-controlled study, patients with glycated haemoglobin (HbA1c) 7-11% and creatinine clearance <50 ml/min were stratified by baseline renal impairment (moderate, severe or end-stage on haemodialysis), and randomized (1 : 1) to saxagliptin 2.5 mg once daily or placebo for 12 weeks. Oral antihyperglycaemic drugs and insulin therapy present at enrolment were continued throughout the study. The absolute change in HbA1c from baseline to week 12 (primary efficacy end-point) was analysed using an analysis of covariance model with last observation carried forward methodology.
Results: A total of 170 patients were randomized and treated. The adjusted mean decrease from baseline to week 12 in HbA1c was statistically significantly greater in the saxagliptin group than in the placebo group; the difference between treatments was -0.42% (95% confidence interval: -0.71 to -0.12%, p = 0.007). Adjusted mean HbA1c decreases from baseline to week 12 were numerically greater with saxagliptin than with placebo in the subgroups of patients with moderate (-0.64 vs. -0.05%) and severe (-0.95 vs. -0.50%) renal impairment. HbA1c reductions were similar between saxagliptin and placebo in the subgroup with end-stage renal disease on haemodialysis (-0.84 vs. -0.87%). Saxagliptin was generally well tolerated; incidences of adverse events and hypoglycaemic events were similar to placebo.
Conclusions: Saxagliptin 2.5 mg once daily is a well-tolerated treatment option for patients with inadequately controlled T2DM and renal impairment.
Trial registration: ClinicalTrials.gov NCT00614939.
© 2011 Blackwell Publishing Ltd.