Saxagliptin Efficacy and Safety in Patients With Type 2 Diabetes and Moderate Renal Impairment.

Abstract

IntroductionType 2 diabetes (T2D) is the leading cause of chronic kidney disease (CKD). The recommended dose of the dipeptidyl peptidase-4 inhibitor saxagliptin is 2.5 mg in patients with moderate or severe renal impairment (creatinine clearance ≤50 mL/min). In this post hoc analysis, we assessed the effect of saxagliptin 2.5 and 5 mg/day versus placebo on glycemic measures in patients with T2D and estimated glomerular filtration rate 45–60 mL/min/1.73 m2.MethodsEfficacy and safety data were pooled from nine 24-week, randomized, placebo-controlled clinical trials.ResultsThe majority (56–61%) of patients were women aged <65 years with glycated hemoglobin (A1C) 8.1–8.2%; half of the patients had a T2D duration ≥5 years. Mean change from baseline in A1C was significantly greater with saxagliptin 2.5 (–0.6%, P = 0.036 vs placebo) and 5 mg/day (–0.9%, P < 0.001 vs placebo) compared with placebo (–0.2%). There were numerically greater reductions in fasting plasma glucose and 2-h postprandial glucose, and a significantly greater proportion of patients achieved A1C <7% with saxagliptin 5 mg/day (44.8%) compared with placebo (20.0%, P = 0.004 vs placebo). The incidence of hypoglycemia was not significantly different across groups (16.2% in the saxagliptin 5-mg/day, 12.2% in the saxagliptin 2.5-mg/day, and 11.3% in the placebo groups).ConclusionThese results suggest that saxagliptin 2.5 and 5 mg/day improve glycemic control and are generally well tolerated in patients with T2D and moderate CKD.Trial registrationClinicalTrials.gov identifier, NCT00121641, NCT00316082, NCT00698932, NCT00918879, NCT00121667, NCT00661362, NCT00313313, NCT00295633, NCT00757588.FundingAstraZeneca, Gaithersburg, MD, USA.