Vildagliptin plus metformin combination therapy provides superior glycaemic control to individual monotherapy in treatment-naive patients with type 2 diabetes mellitus

E. Bosi, F. Dotta, Y. Jia, Matthew Goodman

Research output: Contribution to journalArticlepeer-review

Abstract

Aim: To compare the efficacy and safety of vildagliptin and metformin initial combination therapy with individual monotherapies in treatment-naive patients with type 2 diabetes mellitus (T2DM). Methods: This was a 24-week, randomized, double-blind, active-controlled study. Treatment-naive patients with T2DM who had a glycated haemoglobin (HbA1c) of 7.5-11% (N = 1179) were randomized equally to receive vildagliptin plus high-dose metformin combination therapy (50 mg + 1000 mg twice daily), vildagliptin plus low-dose metformin combination therapy (50 mg + 500 mg twice daily), vildagliptin monotherapy (50 mg twice daily) or high-dose metformin monotherapy (1000 mg twice daily). The primary objective was to demonstrate that HbA1c reduction from baseline with either combination therapy is superior to both monotherapies at the week 24 endpoint. Patients who failed glycaemic-screening criteria [HbA1c >11% or fasting plasma glucose (FPG) >15 mmol/l (270 mg/dl)] could enter a 24-week, single-arm substudy. These patients (N = 94) received open-label vildagliptin plus high-dose metformin combination therapy (100 mg + 1000 mg twice daily). Results: From comparable baseline values (8.6-8.7%), HbA1c decreased in all four treatment groups, to the greatest extent with vildagliptin plus high-dose metformin combination therapy. Mean (SE) HbA1c change from baseline was -1.8% (0.06%), -1.6% (0.06%), -1.1% (0.06%) and -1.4% (0.06%) with vildagliptin plus high-dose metformin combination therapy, vildagliptin plus low-dose metformin combination therapy, and vildagliptin and metformin monotherapies respectively. The between-group difference was superior with vildagliptin plus high-dose metformin combination therapy (p <0.001 vs. both monotherapies) and vildagliptin plus low-dose metformin combination therapy (p <0.001 and p = 0.004, vs. vildagliptin and metformin monotherapies, respectively). Higher baseline HbA 1c values were linked to greater HbA1creductions, with changes of -3.2% (0.22%), -2.7% (0.22%), -1.5% (0.24%) and -2.6% (0.26%) respectively, occurring in patients with baseline HbA1c ≥10%. Reductions in FPG were superior with vildagliptin plus high-dose metformin combination therapy [change from baseline -2.63 (0.13) mmol/l] compared with both monotherapies [-1.26 (0.13) mmol/l and -1.92 (0.13) mmol/l, respectively; p <0.001]. There was no incidence of hypoglycaemia or severe hypoglycaemia with either combination therapy, and neither was associated with weight gain. All treatments were well tolerated and displayed a comparable incidence of adverse events overall. Despite superior HbA1c lowering, the vildagliptin plus low-dose metformin combination therapy group demonstrated a favourable gastrointestinal (GI) tolerability profile compared with metformin monotherapy. Conclusions: In treatment-naive patients, combinations of vildagliptin and both high-dose and low-dose metformin provide superior efficacy to monotherapy treatments with a comparable overall tolerability profile and low risk of hypoglycaemia. The potential dose-sparing effect of adding vildagliptin to low-dose metformin in preference to the up-titration of metformin may allow patients to achieve equivalent or superior HbA 1c lowering without the GI tolerability issues associated with higher doses of metformin.

Original languageEnglish
Pages (from-to)506-515
Number of pages10
JournalDiabetes, Obesity and Metabolism
Volume11
Issue number5
DOIs
Publication statusPublished - 2009

Keywords

  • DPP-4 inhibitor
  • Initial combination therapy
  • Metformin
  • Type 2 diabetes mellitus
  • Vildagliptin

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Fingerprint

Dive into the research topics of 'Vildagliptin plus metformin combination therapy provides superior glycaemic control to individual monotherapy in treatment-naive patients with type 2 diabetes mellitus'. Together they form a unique fingerprint.

Cite this