Long-term treatment with the dipeptidyl peptidase-4 inhibitor saxagliptin in patients with type 2 diabetes mellitus and renal impairment: a randomised controlled 52-week efficacy and safety study

Objective: Therapeutic options are limited for diabetes patients with renal disease. This report presents 52-week results from a study assessing the dipeptidyl peptidase-4 inhibitor saxagliptin in patients with type 2 diabetes mellitus (T2DM) and renal impairment. Design: Double-blind study in patients stratified by baseline renal impairment (moderate, severe or end-stage renal disease [ESRD] on haemodialysis) randomised to saxagliptin 2.5 mg once daily or placebo added to other antidiabetic drugs in use at baseline, including insulin. Patients: A total of 170 adults with glycated haemoglobin (HbA(1c)) 7-11% and creatinine clearance <50 ml/min or ESRD were randomised and treated. Measurements: Absolute changes in HbA1c and fasting plasma glucose (FPG) from baseline to week 52 were evaluated using analysis of covariance (ANCOVA) with last observation carried forward. Repeated-measures analyses were also performed. Results: Adjusted mean decrease in HbA1c was greater with saxagliptin than placebo (difference,) -0.73%, p < 0.001 [ANCOVA]). Reductions in adjusted mean HbA1c were numerically greater with saxagliptin than placebo in patients with renal impairment rated as moderate ( -0.94% vs. 0.19% respectively) or severe (-0.81% vs. -0.49%), but similar to placebo for those with ESRD (-1.13% vs. -0.99%). Reductions in adjusted mean FPG were numerically greater with saxagliptin in patients with moderate or severe renal impairment. Saxagliptin was generally well tolerated; similar proportions of patients in the saxagliptin and placebo groups reported hypoglycaemic events (28% and 29% respectively). Conclusions: Saxagliptin 2.5 mg once daily offers sustained efficacy and good tolerability for patients with T2DM and renal impairment.