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

Int J Clin Pract. 2011 Dec;65(12):1230-9. doi: 10.1111/j.1742-1241.2011.02812.x. Epub 2011 Oct 7.

Abstract

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 HbA(1c) 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 HbA(1c) was greater with saxagliptin than placebo (difference, -0.73%, p < 0.001 [ANCOVA]). Reductions in adjusted mean HbA(1c) 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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adamantane / administration & dosage
  • Adamantane / adverse effects
  • Adamantane / analogs & derivatives*
  • Aged
  • Analysis of Variance
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetic Nephropathies / blood
  • Diabetic Nephropathies / drug therapy*
  • Dipeptides / administration & dosage*
  • Dipeptides / adverse effects
  • Double-Blind Method
  • Fasting / blood
  • Glycated Hemoglobin / metabolism
  • Humans
  • Hypoglycemia / chemically induced
  • Hypoglycemic Agents / administration & dosage*
  • Hypoglycemic Agents / adverse effects
  • Kidney Failure, Chronic / blood
  • Kidney Failure, Chronic / drug therapy*
  • Treatment Outcome

Substances

  • Blood Glucose
  • Dipeptides
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • saxagliptin
  • Adamantane