title: Linagliptin lowers albuminuria on top of recommended standard treatment in patients with type 2 diabetes and renal dysfunction.
abstract: OBJECTIVE
  Preclinical data suggest that linagliptin, a dipeptidyl peptidase-4 inhibitor, may lower urinary albumin excretion. The ability of linagliptin to lower albuminuria on top of renin-angiotensin-aldosterone system (RAAS) inhibition in humans was analyzed by pooling data from four similarly designed, 24-week, randomized, double-blind, placebo-controlled, phase III trials.
  
  
  METHODS
  A pooled analysis of four completed studies identified 217 subjects with type 2 diabetes and prevalent albuminuria (defined as a urinary albumin-to-creatinine ratio [UACR] of 30-3,000 mg/g creatinine) while receiving stable doses of RAAS inhibitors. Participants were randomized to either linagliptin 5 mg/day (n = 162) or placebo (n= 55). The primary end point was the percentage change in geometric mean UACR from baseline to week 24.
  
  
  RESULTS
  UACR at week 24 was reduced by 32% (95% CI -42 to -21; P < 0.05) with linagliptin compared with 6% (95% CI -27 to +23) with placebo, with a between-group difference of 28% (95% CI -47 to -2; P = 0.0357). The between-group difference in the change in HbA1c from baseline to week 24 was -0.61% (-6.7 mmol/mol) in favor of linagliptin (95% CI -0.88 to -0.34% [-9.6 to -3.7 mmol/mol]; P < 0.0001). The albuminuria-lowering effect of linagliptin, however, was not influenced by race or HbA1c and systolic blood pressure (SBP) values at baseline or after treatment.
  
  
  CONCLUSIONS
  Linagliptin administered in addition to stable RAAS inhibitors led to a significant reduction in albuminuria in patients with type 2 diabetes and renal dysfunction. This observation was independent of changes in glucose level or SBP. Further research to prospectively investigate the renal effects of linagliptin is underway.
authors.affiliation: Corresponding author: Per-Henrik Groop, per-henrik.groop@helsinki.fi.
authors.forename: Per-Henrik
authors.initials: PH
authors.lastname: Groop
authors.forename: Mark E
authors.initials: ME
authors.lastname: Cooper
authors.forename: Vlado
authors.initials: V
authors.lastname: Perkovic
authors.forename: Angela
authors.initials: A
authors.lastname: Emser
authors.forename: Hans-Juergen
authors.initials: HJ
authors.lastname: Woerle
authors.forename: Maximilian
authors.initials: M
authors.lastname: von Eynatten
mesh_terms: D000368:Aged; D000419:Albuminuria / Q000188:drug therapy* / Q000209:etiology; D001794:Blood Pressure / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D000069476:Linagliptin; D008297:Male; D008875:Middle Aged; D011687:Purines / Q000627:therapeutic use*; D011799:Quinazolines / Q000627:therapeutic use*; D012084:Renin-Angiotensin System / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D006442:Glycated Hemoglobin; D000069476:Linagliptin; D011687:Purines; D011799:Quinazolines
references.citation: J Am Soc Nephrol. 2009 Aug;20(8):1813-21
references.pmid: 19443635
references.citation: N Engl J Med. 2001 Sep 20;345(12):851-60
references.pmid: 11565517
references.citation: N Engl J Med. 2001 Sep 20;345(12):861-9
references.pmid: 11565518
references.citation: J Pharmacol Exp Ther. 2012 Feb;340(2):248-55
references.pmid: 22025647
references.citation: Diabetes Obes Metab. 2011 Mar;13(3):258-67
references.pmid: 21205122
references.citation: Am J Kidney Dis. 2002 Feb;39(2 Suppl 1):S1-266
references.pmid: 11904577
references.citation: Diabetes Care. 2013 May;36(5):1067-73
references.pmid: 23248197
references.citation: N Engl J Med. 1991 Jun 6;324(23):1626-32
references.pmid: 2030719
references.citation: N Engl J Med. 2008 Jun 12;358(24):2560-72
references.pmid: 18539916
references.citation: Diabetes Care. 2012 Jan;35 Suppl 1:S11-63
references.pmid: 22187469
references.citation: JAMA. 2001 Jul 25;286(4):421-6
references.pmid: 11466120
references.citation: Circulation. 2004 Aug 24;110(8):921-7
references.pmid: 15302780
references.citation: JAMA. 2007 Nov 7;298(17):2038-47
references.pmid: 17986697
references.citation: Lancet. 2010 Jun 12;375(9731):2073-81
references.pmid: 20483451
references.citation: J Am Soc Nephrol. 2007 Apr;18(4):1227-38
references.pmid: 17360951
references.citation: J Am Soc Nephrol. 2005 Oct;16(10):3027-37
references.pmid: 16120823
references.citation: Lancet. 2010 Nov 6;376(9752):1543-51
references.pmid: 21055801
references.citation: Kidney Int. 2006 Jun;69(11):2057-63
references.pmid: 16612330
references.citation: N Engl J Med. 1986 Mar 13;314(11):665-70
references.pmid: 3513009
references.citation: Exp Diabetes Res. 2011;2011:162092
references.pmid: 22203828
references.citation: Diabet Med. 2011 Nov;28(11):1352-61
references.pmid: 21781152
references.citation: Diabetes Obes Metab. 2012 Jun;14(6):565-74
references.pmid: 22356132
references.citation: J Hypertens. 2010 Dec;28(12):2357-69
references.pmid: 20842046
references.citation: Int J Pediatr Nephrol. 1986 Jan-Mar;7(1):31-8
references.pmid: 3957559
references.citation: Kidney Int. 2004 Jun;65(6):2309-20
references.pmid: 15149345
references.citation: J Am Soc Nephrol. 2007 May;18(5):1540-6
references.pmid: 17409317
references.citation: Clin J Am Soc Nephrol. 2006 Jul;1(4):761-7
references.pmid: 17699284
references.citation: Lancet. 2012 Aug 4;380(9840):475-83
references.pmid: 22748821
references.citation: N Engl J Med. 2009 Jul 2;361(1):40-51
references.pmid: 19571282
references.citation: J Clin Invest. 2006 Feb;116(2):288-96
references.pmid: 16453013
references.citation: Kidney Blood Press Res. 2012;36(1):119-30
references.pmid: 23171828
references.citation: Diabetes Care. 2010 Jul;33(7):1536-43
references.pmid: 20413518
references.citation: Diabetes Obes Metab. 2011 Jan;13(1):65-74
references.pmid: 21114605
references.citation: Diabetes Res Clin Pract. 1995 May;28(2):103-17
references.pmid: 7587918
references.citation: Clin Sci (Lond). 2013 Jan;124(1):17-26
references.pmid: 22963445
references.citation: Kidney Blood Press Res. 2012;36(1):65-84
references.pmid: 22947920
references.citation: Metabolism. 2012 Oct;61(10):1422-34
references.pmid: 22554832
references.citation: BMJ. 2000 Aug 12;321(7258):405-12
references.pmid: 10938048