Marcel H A Muskiet1, Lennart Tonneijck2, Mark M Smits2, Mark H H Kramer2, D Margriet Ouwens3,4,5, Bolette Hartmann6, Jens J Holst6, Daan J Touw7, A H Jan Danser8, Jaap A Joles9, Daniël H van Raalte2. 1. Diabetes Center, Amsterdam University Medical Centers, location VUmc, Amsterdam, the Netherlands ma.muskiet@amsterdamumc.nl. 2. Diabetes Center, Amsterdam University Medical Centers, location VUmc, Amsterdam, the Netherlands. 3. Institute of Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Düsseldorf, Germany. 4. German Center for Diabetes Research (DZD), Muenchen-Neuherberg, Germany. 5. Department of Endocrinology, Ghent University Hospital, Ghent, Belgium. 6. Department of Biomedical Sciences, Panum Institute, University of Copenhagen, Copenhagen, Denmark. 7. Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, Groningen, the Netherlands. 8. Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands. 9. Department of Nephrology and Hypertension, University Medical Center, Utrecht, the Netherlands.
Abstract
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 excretions, urinary damage markers, and circulating DPP-4 substrates (among others, glucagon-like peptide 1 and stromal cell-derived factor-1α [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 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-1α (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-1α, likely distal to the macula densa.
RCT Entities:
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 excretions, urinary damage markers, and circulating DPP-4 substrates (among others, glucagon-like peptide 1 and stromal cell-derived factor-1α [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 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-1α (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-1α, likely distal to the macula densa.
Authors: Marcel H A Muskiet; Lennart Tonneijck; Mark M Smits; Mark H H Kramer; D Margriet Ouwens; Bolette Hartmann; Jens J Holst; A H Jan Danser; Jaap A Joles; Daniël H van Raalte Journal: Diabetes Obes Metab Date: 2021-10-06 Impact factor: 6.408