title: Linagliptin treatment in subjects with type 2 diabetes with and without mild-to-moderate renal impairment.
abstract: OBJECTIVE
  Renal disease is a frequent comorbidity of type 2 diabetes mellitus (T2DM) and an important factor complicating the choice of glucose-lowering drugs. The aim of this analysis was to evaluate the efficacy and safety of the dipeptidyl peptidase (DPP)-4 inhibitor linagliptin (5 mg/day) in mono, dual or triple oral glucose-lowering regimens in subjects with T2DM and mild or moderate renal impairment (RI).
  
  
  METHODS
  In this pooled analysis of three 24-week, placebo-controlled, phase 3 trials, subjects with mild (estimated glomerular filtration rate (eGFR) 60-<90 ml/min/1.73 m(2) , n = 838) or moderate RI (30-<60 ml/min/1.73 m(2), n = 93) were compared with subjects with normal renal function (≥90 ml/min/1.73 m(2), n = 1212).
  
  
  RESULTS
  Subjects with RI were older, had longer duration of diabetes, and increased prevalence of diabetes-related comorbidities. After 24 weeks, linagliptin achieved consistent placebo-corrected mean glycated haemoglobin (HbA1c) changes across the three renal function categories: normal (-0.63%; p < 0.0001), mild RI (-0.67%; p < 0.0001) and moderate RI (-0.53%; p < 0.01), with no inter-group difference (p = 0.74). Renal function with linagliptin remained stable across all categories. In linagliptin-treated subjects, overall adverse event (AE) rates and serious AE rates were similar to placebo. The incidence of hypoglycaemia with linagliptin and placebo was 11.1 versus 6.9%, 11.9 versus 9.0% and 15.9 versus 12.0% in the normal, mild RI and moderate RI categories, respectively.
  
  
  CONCLUSIONS
  This pooled analysis provides evidence that linagliptin is an effective, well-tolerated and convenient treatment in subjects with T2DM and mild or moderate RI.
authors.affiliation: Division of Nephrology, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland; Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki, Helsinki, Finland; Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.
authors.forename: P-H
authors.initials: PH
authors.lastname: Groop
authors.forename: S
authors.initials: S
authors.lastname: Del Prato
authors.forename: M-R
authors.initials: MR
authors.lastname: Taskinen
authors.forename: D R
authors.initials: DR
authors.lastname: Owens
authors.forename: Y
authors.initials: Y
authors.lastname: Gong
authors.forename: S
authors.initials: S
authors.lastname: Crowe
authors.forename: S
authors.initials: S
authors.lastname: Patel
authors.forename: M
authors.initials: M
authors.lastname: von Eynatten
authors.forename: H-J
authors.initials: HJ
authors.lastname: Woerle
mesh_terms: D000328:Adult; D000368:Aged; D017326:Clinical Trials, Phase III as Topic; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D003928:Diabetic Nephropathies / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000069476:Linagliptin; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011687:Purines / Q000008:administration & dosage* / Q000009:adverse effects; D011799:Quinazolines / Q000008:administration & dosage* / Q000009:adverse effects; D016032:Randomized Controlled Trials as Topic; D012720:Severity of Illness Index
chemical_list: D007004:Hypoglycemic Agents; D010919:Placebos; D011687:Purines; D011799:Quinazolines; D000069476:Linagliptin
keywords: DPP-4 inhibitor; diabetic nephropathy; glycaemic control; incretin therapy; type 2 diabetes