Safety and efficacy of vildagliptin versus placebo in patients with type 2 diabetes and moderate or severe renal impairment: a prospective 24-week randomized placebo-controlled trial

Diabetes Obes Metab. 2011 Oct;13(10):947-54. doi: 10.1111/j.1463-1326.2011.01467.x.

Abstract

Aim: Assess safety/tolerability and efficacy of the DPP-4 inhibitor vildagliptin in 515 patients with type 2 diabetes mellitus (T2DM) and moderate or severe renal impairment (RI).

Methods: Double-blind, randomized, parallel-group, placebo-controlled, 24-week clinical trial assessing safety and efficacy of vildagliptin (50 mg qd) added to current antidiabetic therapy, in patients with T2DM and moderate or severe RI (GFR ≥ 30 to <50 or <30 ml/min/1.73 m(2) ).

Results: The study population comprised of 165 and 129 patients with moderate RI and 124 and 97 patients with severe RI randomized to vildagliptin and placebo, respectively, with most patients receiving background insulin therapy (68 and 81% for moderate and severe RI, respectively). After 24 weeks, the between-treatment difference in the adjusted mean change in A1C was -0.5 ± 0.1% (p < 0.0001) in moderate RI (baseline A1C = 7.9%) and -0.6 ± 0.1% (p < 0.0001) in severe RI (baseline A1C = 7.7%). In patients with moderate RI, similar proportions of those receiving vildagliptin or placebo experienced any AE (68 vs. 73%), any SAE (9 vs. 9%), any AE leading to discontinuation (3 vs. 5%) or death (1 vs. 1%). This was also true for patients with severe RI: AEs (73 vs. 74%), SAEs (19 vs. 21%), AEs leading to discontinuation (9 vs. 6%) and death (2 vs. 4%).

Conclusions: In this 24-week study of 515 patients with T2DM and moderate or severe RI, vildagliptin added to ongoing antidiabetic therapy had a safety profile similar to placebo. Further, relative to placebo, vildagliptin elicited a statistically and clinically significant decrease in A1C in patients with moderate or severe RI.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adamantane / administration & dosage
  • Adamantane / adverse effects
  • Adamantane / analogs & derivatives*
  • Adamantane / pharmacology
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetic Nephropathies / metabolism*
  • Dipeptidyl-Peptidase IV Inhibitors / administration & dosage
  • Dipeptidyl-Peptidase IV Inhibitors / adverse effects
  • Dipeptidyl-Peptidase IV Inhibitors / pharmacology*
  • Double-Blind Method
  • Female
  • Glycated Hemoglobin / drug effects*
  • Humans
  • Kidney Failure, Chronic / metabolism*
  • Male
  • Middle Aged
  • Nitriles / administration & dosage
  • Nitriles / adverse effects
  • Nitriles / pharmacology*
  • Prospective Studies
  • Pyrrolidines / administration & dosage
  • Pyrrolidines / adverse effects
  • Pyrrolidines / pharmacology*
  • Treatment Outcome
  • Vildagliptin
  • Young Adult

Substances

  • Dipeptidyl-Peptidase IV Inhibitors
  • Glycated Hemoglobin A
  • Nitriles
  • Pyrrolidines
  • Vildagliptin
  • Adamantane