title: Long-term efficacy and safety of linagliptin in patients with type 2 diabetes and severe renal impairment: a 1-year, randomized, double-blind, placebo-controlled study.
abstract: OBJECTIVE
  This placebo-controlled study assessed long-term efficacy and safety of the dipeptidyl peptidase-4 inhibitor linagliptin in patients with type 2 diabetes and severe renal impairment (RI).
  
  
  METHODS
  In this 1-year, double-blind study, 133 patients with type 2 diabetes (HbA(1c) 7.0-10.0%) and severe RI (estimated glomerular filtration rate [eGFR] <30 mL/min/1.73 m(2)) at screening were randomized to linagliptin 5 mg (n = 68) or placebo (n = 65) once daily, added to existing background therapy. The primary efficacy end point was HbA(1c) change from baseline to week 12. Efficacy and safety end points were assessed after 1 year.
  
  
  RESULTS
  At week 12, adjusted mean HbA(1c) decreased by -0.76% with linagliptin and -0.15% with placebo (treatment difference, -0.60%; 95% CI -0.89 to -0.31; P < 0.0001). HbA(1c) improvements were sustained with linagliptin (-0.71%) over placebo (0.01%) at 1 year (treatment difference -0.72%, -1.03 to -0.41; P < 0.0001). Mean insulin doses decreased by -6.2 units with linagliptin and -0.3 units with placebo. Overall adverse event incidence was similar over 1 year (94.1 vs. 92.3%). Incidence of severe hypoglycemia with linagliptin and placebo was comparably low (three patients per group). Linagliptin and placebo had little effect on renal function (median change in eGFR, -0.8 vs. -2.2 mL/min/1.73 m(2)), and no drug-related renal failure occurred.
  
  
  CONCLUSIONS
  In patients with type 2 diabetes and severe RI, linagliptin provided clinically meaningful improvements in glycemic control with very low risk of severe hypoglycemia, stable body weight, and no cases of drug-related renal failure. The potential for linagliptin to spare insulin and provide long-term renal safety warrants further investigations.
authors.affiliation: Division of Endocrinology, Metabolism and Lipid Research, Washington University in St. Louis, St. Louis, MO, USA. jmcgill@dom.wustl.edu
authors.forename: Janet B
authors.initials: JB
authors.lastname: McGill
authors.forename: Lance
authors.initials: L
authors.lastname: Sloan
authors.forename: Jennifer
authors.initials: J
authors.lastname: Newman
authors.forename: Sanjay
authors.initials: S
authors.lastname: Patel
authors.forename: Christophe
authors.initials: C
authors.lastname: Sauce
authors.forename: Maximilian
authors.initials: M
authors.lastname: von Eynatten
authors.forename: Hans-Juergen
authors.initials: HJ
authors.lastname: Woerle
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D004311:Double-Blind Method; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects; D000069476:Linagliptin; D008297:Male; D008875:Middle Aged; D011687:Purines / Q000009:adverse effects* / Q000627:therapeutic use*; D011799:Quinazolines / Q000009:adverse effects* / Q000627:therapeutic use*; D051437:Renal Insufficiency / Q000188:drug therapy* / Q000378:metabolism; D055815:Young Adult
chemical_list: D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000069476:Linagliptin; D011687:Purines; D011799:Quinazolines