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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

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posted on 09.09.2020 by Marcel H.A. Muskiet, Lennart Tonneijck, Mark M. Smits, Mark H.H. Kramer, D. Margriet Ouwens, Bolette Hartmann, Jens J. Holst, Daan J. Touw, A.H. Jan Danser, Jaap A. Joles, Daniël H. van Raalte
OBJECTIVE To compare effects of the DPP-4 inhibitor linagliptin , with a sulfonylurea on renal physiology in metformin-treated T2DM-patients.

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.

Funding

Funding for the study was provided by Boehringer Ingelheim. The funder had no role in the study design, the analyses or interpretation of the data, or drafting the manuscript. The funder had no role in the decision to submit this manuscript for publication.

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