Effects of DPP-4 Inhibitor Linagliptin versus Sulfonylurea Glimepiride as Add-On to Metformin on Renal Physiology in Overweight Patients with Type 2 Diabetes (RENALIS): A Randomized, Double-Blind Trial
RESEARCH-DESIGN AND METHODS In this double-blind randomized trial, 46 overweight T2DM-patients without renal impairment received once-daily linagliptin (5mg) or glimepiride (1mg) for 8 weeks. Fasting GFR and effective renal plasma flow (ERPF) were determined by inulin and para-aminohippuric-acid clearances. Fractional excretions (FE), urinary damage-markers, and circulating DPP-4-substrates (a.o. GLP-1, and SDF-1α) were measured.
RESULTS HbA1c-reductions were similar with linagliptin (–0.45±0.09%) and glimepiride (–0.65±0.10%) after 8 weeks (P=0.101). Linagliptin versus glimepiride did not affect GFR, ERPF, estimated intrarenal hemodynamics or damage-makers. Only linagliptin increased FENa and FEK, without affecting FELithium. Linagliptin-induced change in FENa correlated with SDF-1α (R=0.660), but not with other DPP-4-substrates.
CONCLUSIONS Linagliptin does not affect fasting renal hemodynamics compared to glimepiride in T2DM patient. DPP-4-inhibition promotes modest natriuresis, possibly mediated by SDF-1α, likely distal to the macula-densa.
