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.

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.

• Authors: 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
• Journal: Diabetes care (Diabetes Care) Vol. 43 Issue 11 Pg. 2889-2893 (11 2020) ISSN: 1935-5548 [Electronic] United States
• PMID: 32900785 (Publication Type: Clinical Trial, Phase IV, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 by the American Diabetes Association.

Chemical References

• CXCL12 protein, human
• Chemokine CXCL12
• Dipeptidyl-Peptidase IV Inhibitors
• Glycated Hemoglobin A
• Sulfonylurea Compounds
• hemoglobin A1c protein, human
• Linagliptin
• glimepiride
• Metformin
• DPP4 protein, human
• Dipeptidyl Peptidase 4

Topics

• Adult
• Aged
• Chemokine CXCL12 (blood)
• Diabetes Mellitus, Type 2 (blood, complications, drug therapy)
• Dipeptidyl Peptidase 4 (blood)
• Dipeptidyl-Peptidase IV Inhibitors (administration & dosage, adverse effects)
• Double-Blind Method
• Drug Therapy, Combination (adverse effects)
• Female
• Glomerular Filtration Rate
• Glycated Hemoglobin (analysis)
• Humans
• Kidney (drug effects)
• Linagliptin (administration & dosage, adverse effects)
• Male
• Metformin (adverse effects)
• Middle Aged
• Natriuresis (drug effects)
• Overweight (complications)
• Sulfonylurea Compounds (administration & dosage, adverse effects)
• Treatment Outcome