Despite optimal therapy, people with type 2 diabetes (T2D) remain at high risk for kidney damage, manifest as
albuminuria, and many develop progressive renal failure. Linagliptin, a DPP-4 inhibitor, has previously shown
evidence of reducing albuminuria on top of telmisartan in mice. We explored the clinical effect of linagliptin on
albuminuria in T2D patients with early diabetic nephropathy. Four randomized, double-blind, 24-week, placebocontrolled trials of linagliptin on no, mono, or dual oral glucose-lowering background therapy had data available for urinary albumin-to-creatinine ratio (UACR) and were pooled for analysis (n=2472). Participants were included in this analysis if they had: i) 30≤UACR≤3000 mg/g creatinine; ii) stable treatment with ACE/ARBs ≥4 weeks prior and during the trial; and iii) eGFR >30 mL/min/1.73 m². The endpoint was the percentage change in geometric mean UACR. In this analysis, 492 (19.9%) patients met UACR and eGFR thresholds of whom 46% received stable ACE/ARB therapy (linagliptin n=168; placebo n=59). Mean baseline HbA1c and median UACR were 8.2% vs 8.5% and 76 vs 78 mg/g creatinine for the linagliptin and placebo groups, respectively. After 24 weeks, placebo-corrected changes in HbA1c and FPG were -0.71% and -26 mg/dL, respectively (both p<.0001). Linagliptin significantly lowered adjusted UACR by 33% (95% CI: 22 to 42%; p<.05) with a between group difference vs placebo of -29% (-3 to -48%; p<.05). Overall, kidney function and blood pressure were unchanged although more patients on placebo received new anti-hypertensive drugs (17% vs 11% with linagliptin). Sensitivity analyses in patients not previously treated with RAS blockade (n=265) found similar results. Linagliptin may have kidney-protective properties beyond glucose-lowering effects. Further investigation of the potential kidney benefits is underway.

This abstract is an encore submission of the abstract that was presented at the American Diabetes Association meeting of 2012.