Safety and tolerability of linagliptin: a pooled analysis of data from randomized controlled trials in 3572 patients with type 2 diabetes mellitus

Diabetes Obes Metab. 2012 May;14(5):470-8. doi: 10.1111/j.1463-1326.2012.01565.x. Epub 2012 Feb 16.

Abstract

Aims: To assess the safety and tolerability of the dipeptidyl peptidase-4 inhibitor linagliptin in patients with type 2 diabetes.

Methods: Data were pooled from eight randomized, double-blind, placebo-controlled Phase III clinical trials lasting ≤24 weeks. Incidences were calculated with descriptive statistics for the overall population and for subgroups of elderly and renally impaired patients.

Results: A total of 2523 patients received linagliptin 5 mg once daily and 1049 patients received placebo. The overall incidence of adverse events (AEs) or serious AEs with linagliptin was similar to placebo (AEs 55.8% vs. 55.0%; serious AEs 2.8% vs. 2.7%). Overall aggregated infection incidence was 19.5% for linagliptin and 21.4% for placebo. Similar or reduced incidence of AEs versus placebo were seen with linagliptin for upper respiratory tract infection (3.3% vs. 4.9%), headache (2.9% vs. 3.1%), urinary tract infection (2.2% vs. 2.7%), blood and lymphatic disorders (1.0% vs. 1.2%), hypersensitivity (0.1% vs. 0.1%), hepatic enzyme increase (0.1% and 0.1%) and serum creatinine increase (0.0% and 0.1%). There was a slight increased frequency of nasopharyngitis (5.9% vs. 5.1%) and cough (1.7% vs. 1.0%) with linagliptin. Hypoglycaemia incidence was 8.2% for linagliptin and 5.1% for placebo; incidence was higher in patients with a background of sulphonylurea therapy (20.7% and 13.3%, respectively). In patients not receiving concomitant sulphonylurea, the hypoglycaemic incidence with linagliptin was very low in both the total population (<1%), and elderly and renally impaired patients (both <1%).

Conclusions: This pooled analysis shows that linagliptin is well tolerated, with a low risk of hypoglycaemia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Glucose / drug effects*
  • Clinical Trials, Phase III as Topic
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use*
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Linagliptin
  • Male
  • Middle Aged
  • Purines / therapeutic use*
  • Quinazolines / therapeutic use*
  • Randomized Controlled Trials as Topic
  • Sulfonylurea Compounds / therapeutic use

Substances

  • Blood Glucose
  • Dipeptidyl-Peptidase IV Inhibitors
  • Hypoglycemic Agents
  • Purines
  • Quinazolines
  • Sulfonylurea Compounds
  • Linagliptin