Efficacy and safety of linagliptin in persons with type 2 diabetes inadequately controlled by a combination of metformin and sulphonylurea: a 24-week randomized study

Diabet Med. 2011 Nov;28(11):1352-61. doi: 10.1111/j.1464-5491.2011.03387.x.

Abstract

Aims: To examine the efficacy and safety of the dipeptidyl peptidase-4 inhibitor linagliptin in persons with Type 2 diabetes mellitus inadequately controlled [HbA(1c) 53-86 mmol/mol (7.0-10.0%)] by metformin and sulphonylurea combination treatment.

Methods: A multi-centre, 24-week, randomized, double-blind, parallel-group study in 1058 patients comparing linagliptin (5 mg once daily) and placebo when added to metformin plus sulphonylurea. The primary endpoint was the change in HbA(1c) after 24 weeks.

Results: At week 24, the linagliptin placebo-corrected HbA(1c) adjusted mean change from baseline was -7 mmol/mol (-0.62%) [95% CI -8 to -6 mmol/mol (-0.73 to -0.50%); P < 0.0001]. More participants with baseline HbA(1c) ≥ 53 mmol/mol (≥ 7.0%) achieved an HbA(1c) < 53 mmol/mol (<7.0%) with linagliptin compared with placebo (29.2% vs. 8.1%, P< 0.0001). Fasting plasma glucose was reduced with linagliptin relative to placebo (-0.7 mmol/l, 95% CI -1.0 to -0.4; P<0.0001). Improvements in homeostasis model assessment of β-cell function were seen with linagliptin (P<0.001). The proportion of patients who reported a severe adverse event was low in both groups (linagliptin 2.4%; placebo 1.5%). Symptomatic hypoglycaemia occurred in 16.7 and 10.3% of the linagliptin and placebo groups, respectively. Hypoglycaemia was generally mild or moderate; severe hypoglycaemia was reported in 2.7 and 4.8% of the participants experiencing hypoglycaemic episodes in the linagliptin and placebo groups, respectively. No significant weight changes were noted.

Conclusions: In patients with Type 2 diabetes, adding linagliptin to metformin given in combination with a sulphonylurea significantly improved glycaemic control and this was well tolerated. Linagliptin could provide a valuable treatment option for individuals with inadequate glycaemic control despite ongoing combination therapy with metformin and a sulphonylurea.

Trial registration: ClinicalTrials.gov NCT00602472.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers / blood
  • Blood Glucose / metabolism
  • Body Mass Index
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Dipeptidyl-Peptidase IV Inhibitors / administration & dosage
  • Dipeptidyl-Peptidase IV Inhibitors / adverse effects
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use*
  • Double-Blind Method
  • Drug Therapy, Combination
  • Fasting
  • Female
  • Glycated Hemoglobin A / drug effects
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / therapeutic use*
  • Linagliptin
  • Male
  • Metformin / administration & dosage*
  • Middle Aged
  • Purines / administration & dosage
  • Purines / adverse effects
  • Purines / therapeutic use*
  • Quinazolines / administration & dosage
  • Quinazolines / adverse effects
  • Quinazolines / therapeutic use*
  • Sulfonylurea Compounds / administration & dosage*
  • Treatment Outcome
  • Young Adult

Substances

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

Associated data

  • ClinicalTrials.gov/NCT00602472