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

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

6 Citaten (Scopus)
31 Downloads (Pure)


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.

Originele taal-2English
Pagina's (van-tot)2889-2893
Aantal pagina's5
TijdschriftDiabetes Care
Nummer van het tijdschrift10
Vroegere onlinedatum8-sep-2020
StatusPublished - nov-2020

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