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

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

*Corresponding author for this work

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OBJECTIVE To compare effects of the dipeptidyl peptidase 4 (DPP-4) inhibitor linagliptin with those of a sulfonylurea on renal physiology in metformin-treated patients with type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS In this double-blind randomized trial, 46 overweight T2DM patients without renal impairment received once-daily linagliptin (5 mg) or glimepiride (1 mg) for 8 weeks. Fasting glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were determined by inulin and para-aminohippuric acid clearances. Fractional excre-tions, urinary damage markers, and circulating DPP-4 substrates (among others, glucagon-like peptide 1 and stromal cell–derived factor-1a [SDF-1a]) 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 markers. Only linagliptin increased fractional excretion (FE) of sodium (FENa) and potassium, without affecting FE of lithium. Linagliptin-induced change in FENa correlated with SDF-1a (R = 0.660) but not with other DPP-4 substrates. CONCLUSIONS Linagliptin does not affect fasting renal hemodynamics compared with glimepiride in T2DM patients. DPP-4 inhibition promotes modest natriuresis, possibly mediated by SDF-1a, likely distal to the macula densa.

Original languageEnglish
Pages (from-to)2889-2893
Number of pages5
JournalDiabetes Care
Issue number10
Early online date8-Sept-2020
Publication statusPublished - Nov-2020



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