title: Efficacy and Cardiovascular Safety of Linagliptin as an Add-On to Insulin in Type 2 Diabetes: A Pooled Comprehensive Post Hoc Analysis.
abstract: OBJECTIVE
  With the expanding armamentarium of noninsulin therapies for type 2 diabetes mellitus, the use of insulin with various oral agents is becoming more common. In this study, we assessed the efficacy and cardiovascular (CV) safety of the dipeptidyl peptidase-4 inhibitor linagliptin as add-on to insulin in patients with type 2 diabetes.
  
  
  METHODS
  In this post hoc analysis, data for patients receiving basal or basal-bolus insulin were pooled from 4 randomized, double-blind, phase 3 clinical trials of linagliptin 5 mg once daily or placebo given as add-on to background glucose-lowering treatment. Changes in glycated hemoglobin (A1C) and CV risk factors were assessed from baseline to end of trial. The primary CV endpoint was a composite of CV death, nonfatal myocardial infarction, nonfatal stroke and hospitalization due to unstable angina.
  
  
  RESULTS
  The number of patients receiving basal or basal-bolus insulin as background therapy was 1613 (linagliptin: n=811; placebo: n=802). The placebo-adjusted mean (SE) change from baseline in A1C was -0.41 (0.05)% (95% CI -0.50, -0.32; p<0.0001). Treatment with linagliptin provided a relative weight benefit and reduced insulin requirements without affecting blood pressure, heart rate or lipids. The incidence of hypoglycemia with linagliptin was similar to that for placebo (38.7% vs. 39.4%, respectively). The hazard ratio (HR) for the primary endpoint showed that treatment with linagliptin was not associated with an increased CV risk (HR 1.07 [95% CI 0.62, 1.85]).
  
  
  CONCLUSIONS
  Linagliptin, when added to ongoing insulin treatment in patients with type 2 diabetes, improves glycemic control and has a neutral impact on major adverse CV events.
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada; University of Toronto, Toronto, Ontario, Canada. Electronic address: zinman@lunenfeld.ca.
authors.forename: Bernard
authors.initials: B
authors.lastname: Zinman
authors.affiliation: Department of Clinical Sciences, Lund University, Lund, Sweden.
authors.forename: Bo
authors.initials: B
authors.lastname: Ahrén
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Neubacher
authors.affiliation: Boehringer Ingelheim Ltd, Bracknell, United Kingdom.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Patel
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
authors.forename: Hans-Juergen
authors.initials: HJ
authors.lastname: Woerle
authors.affiliation: Boehringer Ingelheim Norway KS, Asker, Norway.
authors.forename: Odd Erik
authors.initials: OE
authors.lastname: Johansen
mesh_terms: D000368:Aged; D002318:Cardiovascular Diseases / Q000150:complications / Q000453:epidemiology / Q000401:mortality / Q000517:prevention & control*; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D003925:Diabetic Angiopathies / Q000453:epidemiology / Q000401:mortality / Q000517:prevention & control; D058065:Diabetic Cardiomyopathies / Q000453:epidemiology / Q000401:mortality / Q000517:prevention & control; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D006943:Hyperglycemia / Q000517:prevention & control*; D007003:Hypoglycemia / Q000139:chemically induced / Q000517:prevention & control*; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use; D007328:Insulin / Q000009:adverse effects / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D000069476:Linagliptin / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009026:Mortality; D012307:Risk Factors
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D000069476:Linagliptin; C517652:hemoglobin A1c protein, human
keywords: DPP-4 inhibitor; cardiovascular risk; diabète sucré de type 2; inhibiteur de la DPP-4; insulin; insuline; linagliptin; linagliptine; risque cardiovasculaire; type 2 diabetes mellitus