title: Safety and tolerability of linagliptin: a pooled analysis of data from randomized controlled trials in 3572 patients with type 2 diabetes mellitus.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Medicine I, Rudolfstiftung Hospital, Vienna, Austria. guntram@schernthaner.eu
authors.forename: G
authors.initials: G
authors.lastname: Schernthaner
authors.forename: A H
authors.initials: AH
authors.lastname: Barnett
authors.forename: A
authors.initials: A
authors.lastname: Emser
authors.forename: S
authors.initials: S
authors.lastname: Patel
authors.forename: J
authors.initials: J
authors.lastname: Troost
authors.forename: H-J
authors.initials: HJ
authors.lastname: Woerle
authors.forename: M
authors.initials: M
authors.lastname: von Eynatten
mesh_terms: D001786:Blood Glucose / Q000187:drug effects*; D017326:Clinical Trials, Phase III as Topic; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D000069476:Linagliptin; D008297:Male; D008875:Middle Aged; D011687:Purines / Q000627:therapeutic use*; D011799:Quinazolines / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D013453:Sulfonylurea Compounds / Q000627:therapeutic use
chemical_list: D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D011687:Purines; D011799:Quinazolines; D013453:Sulfonylurea Compounds; D000069476:Linagliptin