Linagliptin lowers albuminuria on top of recommended standard treatment in patients with type 2 diabetes and renal dysfunction

Per Henrik Groop, Mark E. Cooper, Vlado Perkovic, Angela Emser, Hans-Juergen Woerle, Maximilian Von Eynatten

Research output: Contribution to journalArticleResearchpeer-review

215 Citations (Scopus)


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 reninangiotensin- 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. RESEARCH DESIGN AND 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 3023,000mg/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 242 to 221; P < 0.05) with linagliptin compared with 6% (95% CI 227 to +23) with placebo, with a between-group difference of 28% (95% CI 247 to 22; P = 0.0357). The between-group difference in the change in HbA1c from baseline to week 24 was 20.61% (26.7 mmol/mol) in favor of linagliptin (95% CI 20.88 to 20.34% [29.6 to 23.7 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.

Original languageEnglish
Pages (from-to)3460-3468
Number of pages9
JournalDiabetes Care
Issue number11
Publication statusPublished - Nov 2013
Externally publishedYes

Cite this