Efficacy and safety of vildagliptin in patients with type 2 diabetes mellitus inadequately controlled with dual combination of metformin and sulphonylurea

Diabetes Obes Metab. 2014 May;16(5):403-9. doi: 10.1111/dom.12229. Epub 2013 Dec 2.

Abstract

Aim: The broadly used combination of metformin and sulphonylurea (SU) often fails to bring patients to glycaemic goal. This study assessed the efficacy and safety of vildagliptin as add-on therapy to metformin plus glimepiride combination in patients with type 2 diabetes mellitus (T2DM) who had inadequate glycaemic control.

Methods: A multicentre, double-blind, placebo-controlled study randomized patients to receive treatment with vildagliptin 50 mg bid (n = 158) or placebo (n = 160) for 24 weeks.

Results: After 24 weeks, the adjusted mean change in haemoglobin A1c (HbA1c) was -1.01% with vildagliptin (baseline 8.75%) and -0.25% with placebo (baseline 8.80%), with a between-treatment difference of -0.76% (p < 0.001). Significantly more patients on vildagliptin achieved the HbA1c target <7% (28.3% vs. 5.6%; p < 0.001). The difference in fasting plasma glucose reduction between vildagliptin and placebo was -1.13 mmol/l (p < 0.001). In subgroup of patients with baseline HbA1c ≤8%, vildagliptin reduced HbA1c by 0.74% from baseline 7.82% (between-treatment difference: -0.97%; p < 0.001) with significantly more patients achieving the HbA1c target <7% (38.6% vs. 13.9%; p = 0.014). Vildagliptin was well tolerated with low incidence of hypoglycaemia, slightly higher than with placebo (5.1% vs. 1.9%) and no clinically relevant weight gain.

Conclusions: Vildagliptin significantly improved glycaemic control in patients with T2DM inadequately controlled with metformin plus glimepiride combination. The addition of vildagliptin was well tolerated with low risk of hypoglycaemia and weight gain. This makes vildagliptin an attractive treatment option for patients failing on metformin plus SU particularly in patients with baseline HbA1c ≤8%.

Keywords: DPP-4 inhibitor; glimepiride; metformin; oral antidiabetic drug; type 2 diabetes; vildagliptin.

Publication types

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

MeSH terms

  • Adamantane / administration & dosage
  • Adamantane / adverse effects
  • Adamantane / analogs & derivatives*
  • Adamantane / therapeutic use
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Body Weight / drug effects
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Glycated Hemoglobin / drug effects*
  • Glycated Hemoglobin / metabolism
  • Humans
  • Hypoglycemia / blood
  • Hypoglycemia / drug therapy*
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / therapeutic use*
  • Male
  • Metformin / therapeutic use*
  • Middle Aged
  • Nitriles / administration & dosage
  • Nitriles / adverse effects
  • Nitriles / therapeutic use*
  • Pyrrolidines / administration & dosage
  • Pyrrolidines / adverse effects
  • Pyrrolidines / therapeutic use*
  • Sulfonylurea Compounds / therapeutic use*
  • Treatment Outcome
  • Vildagliptin

Substances

  • Blood Glucose
  • Dipeptidyl-Peptidase IV Inhibitors
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Nitriles
  • Pyrrolidines
  • Sulfonylurea Compounds
  • hemoglobin A1c protein, human
  • Metformin
  • Vildagliptin
  • Adamantane