title: Efficacy and safety of linagliptin in type 2 diabetes subjects at high risk for renal and cardiovascular disease: a pooled analysis of six phase III clinical trials.
abstract: BACKGROUND
  In patients with type 2 diabetes mellitus (T2DM), hypertension and microalbuminuria are predictive markers for increased renal and cardiovascular risk. This post hoc analysis of data from a global development program aimed to evaluate the efficacy and safety of linagliptin in a population with joint prevalence of these two vascular risk factors.
  
  
  METHODS
  Data for patients with baseline microalbuminuria (urine albumin-to-creatinine ratio 30-300 mg/g) and hypertension (systolic blood pressure ≥ 140 mm Hg and/or diastolic blood pressure ≥ 90 mm Hg and/or a history of hypertension; and/or an antihypertensive treatment at baseline) who participated in any of six randomized, placebo-controlled, phase III trials were analyzed. Participants received linagliptin 5 mg daily (alone or in combination with other oral antidiabetic drugs) or placebo for 18 to 24 weeks.
  
  
  RESULTS
  Of 3,119 patients, 512 had both microalbuminuria and hypertension (linagliptin, 366; placebo, 146). Baseline mean (SD) HbA1c was 8.3 (0.9)% and 8.4 (0.9)%; median (range) urine albumin-to-creatinine ratio was 60 (30-292) mg/g and 64 (30-298) mg/g; mean (SD) systolic blood pressure was 138 (15) mm Hg and 135 (16) mm Hg; and mean (SD) diastolic blood pressure was 81 (10) mm Hg and 81 (10) mm Hg, for linagliptin and placebo, respectively. Placebo-corrected mean change in HbA1c from baseline to week 18 and week 24 was -0.57% (95% CI: -0.75, -0.39; P < 0.0001) and -0.59% (95% CI: -0.80, -0.39; P < 0.0001), respectively. Placebo-corrected mean change in FPG from baseline to week 24 was -21.3 mg/dl (95% CI: -31.0, -11.6; P < 0.0001). The incidence of drug-related adverse events was similar for linagliptin and placebo (10.4% and 8.2%, respectively). Changes in systolic and diastolic blood pressure, cholesterol and triglyceride levels were similar between linagliptin and placebo.
  
  
  CONCLUSIONS
  In T2DM patients with the two common vascular risk factors of hypertension and microalbuminuria, linagliptin achieved significant improvements in glycemic control. In this vulnerable patient population at high risk for micro- and macrovascular complications, linagliptin was well tolerated.
authors.affiliation: Boehringer Ingelheim Pharmaceuticals, 900 Ridgebury Road, P,O, Box 368, Ridgefield, CT 06877, USA. maximilian.eynatten@boehringer-ingelheim.com
authors.forename: Maximilian
authors.initials: M
authors.lastname: von Eynatten
authors.forename: Yan
authors.initials: Y
authors.lastname: Gong
authors.forename: Angela
authors.initials: A
authors.lastname: Emser
authors.forename: Hans-Juergen
authors.initials: HJ
authors.lastname: Woerle
mesh_terms: D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000453:epidemiology; D017326:Clinical Trials, Phase III as Topic / Q000379:methods; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000453:epidemiology; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007674:Kidney Diseases / Q000188:drug therapy* / Q000453:epidemiology; D000069476:Linagliptin; D011687:Purines / Q000627:therapeutic use*; D011799:Quinazolines / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic / Q000379:methods; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D007004:Hypoglycemic Agents; D011687:Purines; D011799:Quinazolines; D000069476:Linagliptin