Initial combination of linagliptin and metformin improves glycaemic control in type 2 diabetes: a randomized, double-blind, placebo-controlled study

Diabetes Obes Metab. 2012 Jun;14(6):565-74. doi: 10.1111/j.1463-1326.2012.01590.x. Epub 2012 Mar 21.

Abstract

Aims: To evaluate the efficacy and safety of initial combination therapy with linagliptin plus metformin versus linagliptin or metformin monotherapy in patients with type 2 diabetes.

Methods: In this 24-week, double-blind, placebo-controlled, Phase III trial, 791 patients were randomized to one of six treatment arms. Two free combination therapy arms received linagliptin 2.5 mg twice daily (bid) + either low (500 mg) or high (1000 mg) dose metformin bid. Four monotherapy arms received linagliptin 5 mg once daily, metformin 500 mg or 1000 mg bid or placebo. Patients with haemoglobin A1c (HbA1c) ≥11.0% were not eligible for randomization and received open-label linagliptin + high-dose metformin.

Results: The placebo-corrected mean (95% confidence interval) change in HbA1c from baseline (8.7%) to week 24 was -1.7% (-2.0, -1.4) for linagliptin + high-dose metformin, -1.3% (-1.6, -1.1) for linagliptin + low-dose metformin, -1.2% (-1.5, -0.9) for high-dose metformin, -0.8% (-1.0, -0.5) for low-dose metformin and -0.6 (-0.9, -0.3) for linagliptin (all p < 0.0001). In the open-label arm, the mean change in HbA1c from baseline (11.8%) was -3.7%. Hypoglycaemia occurred at a similar low rate with linagliptin + metformin (1.7%) as with metformin alone (2.4%). Adverse event rates were comparable across treatment arms. No clinically significant changes in body weight were noted.

Conclusions: Initial combination therapy with linagliptin plus metformin was superior to metformin monotherapy in improving glycaemic control, with a similar safety and tolerability profile, no weight gain and a low risk of hypoglycaemia.

Publication types

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

MeSH terms

  • Blood Glucose / drug effects
  • Blood Glucose / metabolism*
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Dipeptidyl-Peptidase IV Inhibitors / administration & dosage*
  • Dipeptidyl-Peptidase IV Inhibitors / pharmacology
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Glycated Hemoglobin A / drug effects
  • Glycated Hemoglobin A / metabolism*
  • Humans
  • Hypoglycemic Agents / administration & dosage*
  • Hypoglycemic Agents / pharmacology
  • Linagliptin
  • Male
  • Metformin / administration & dosage*
  • Metformin / pharmacology
  • Middle Aged
  • Purines / administration & dosage*
  • Purines / pharmacology
  • Quinazolines / administration & dosage*
  • Quinazolines / pharmacology
  • Treatment Outcome

Substances

  • Blood Glucose
  • Dipeptidyl-Peptidase IV Inhibitors
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Purines
  • Quinazolines
  • hemoglobin A1c protein, human
  • Linagliptin
  • Metformin