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

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.

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 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.