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

• Published in: Diabetes, obesity & metabolism Vol. 14; no. 5; pp. 470 - 478
• Main Authors: Schernthaner, G., Barnett, A. H., Emser, A., Patel, S., Troost, J., Woerle, H.-J., von Eynatten, M.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.05.2012; Wiley Subscription Services, Inc
• Subjects: Blood Glucose - drug effects; Clinical trials; Clinical Trials, Phase III as Topic; Cough; Creatinine; Diabetes; diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - drug therapy; dipeptidyl peptidase-4; Dipeptidyl-Peptidase IV Inhibitors - therapeutic use; Dose-Response Relationship, Drug; DPP-4 inhibitor; elderly; Enzymes; Female; Humans; hypoglycaemia; Hypoglycemia; Hypoglycemic Agents - therapeutic use; infection; Infections; Linagliptin; Male; Metabolism; Middle Aged; Placebos; Purines - therapeutic use; Quinazolines - therapeutic use; Randomized Controlled Trials as Topic; Respiratory tract; Respiratory tract infection; Rhinopharyngitis; safety; Side effects; Statistical analysis; Sulfonylurea Compounds - therapeutic use; type 2 diabetes; Urinary tract; Urine
• ISSN: 1462-8902; 1463-1326
• DOI: 10.1111/j.1463-1326.2012.01565.x

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.