Postprandial renal haemodynamic effects of the dipeptidyl peptidase-4 inhibitor linagliptin versus the sulphonylurea glimepiride in adults with type 2 diabetes (RENALIS): A predefined substudy of 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, A. H.Jan Danser, Jaap A. Joles, Daniël H. van Raalte

*Corresponding author for this work

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Abstract

Aim: To determine the effect of the dipeptidyl peptidase-4 inhibitor linagliptin on postprandial glomerular hyperfiltration compared with the sulphonylurea glimepiride in adults with type 2 diabetes (T2D). Materials and Methods: In this predefined substudy within a randomized, double-blind, parallel-group, intervention trial, overweight people with T2D without renal impairment were treated with once-daily linagliptin 5 mg (N = 10) or glimepiride 1 mg (N = 13) as an add-on to metformin for 8 weeks. After a standardized liquid protein-rich meal, the glomerular filtration rate (GFR) and effective renal plasma flow were determined by inulin and para-aminohippuric acid clearance, respectively, based on timed urine sampling. Intrarenal haemodynamics were estimated using the Gomez equations. Glucoregulatory/vasoactive hormones, urinary pH and fractional excretions (FE) of sodium, potassium and urea were measured. Results: Compared with glimepiride, linagliptin increased the postprandial filtration fraction (FF; mean difference 2.1%-point; P =.016) and estimated glomerular hydraulic pressure (mean difference 3.0 mmHg; P =.050), and tended to increase GFR (P =.08) and estimated efferent renal arteriolar resistance (RE; P =.08) from baseline to week 8. No differences in FE were noted. Glimepiride reduced HbA1c more than linagliptin (mean difference −0.40%; P =.004), without between-group differences in time-averaged postprandial glucose levels. In the linagliptin group, change in FF correlated with change in mean arterial pressure (R = 0.807; P =.009) and time-averaged mean glucagon (R = 0.782; P =.008), but not with changes in glucose, insulin, intact glucagon-like peptide-1, renin or FENa. Change in glucagon was associated with change in RE (R = 0.830; P =.003). Conclusions: In contrast to our hypothesis, compared with glimepiride, linagliptin does not reduce postprandial hyperfiltration, yet appears to increase FF after meal ingestion by increasing blood pressure or RE.

Original languageEnglish
Pages (from-to)115-124
Number of pages10
JournalDiabetes, Obesity and Metabolism
Volume24
Issue number1
Early online date28 Sept 2021
DOIs
Publication statusPublished - Jan 2022

Bibliographical note

Funding Information:
M.H.A.M. is a speaker/consultant for AstraZeneca, Eli Lilly & Co., Novo Nordisk, and Sanofi. L.T. consulted for Eli Lilly & Co. and Novo Nordisk. Through M.H.H.K., the Amsterdam University Medical Centers, location VUMC, received research grants from Boehringer Ingelheim, Novo Nordisk, and Sanofi. D.H.v.R. serves on advisory boards of Boehringer Ingelheim, Eli Lilly Alliance, Novo Nordisk, Sanofi, and Merck Sharp & Dohme (MSD), and received research grants from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Sanofi, and MSD. J.J.H. has been a member of advisory boards for Novo Nordisk. No other potential conflicts of interest relevant to this article were reported.

Publisher Copyright:
© 2021 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

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