Postprandial renal haemodynamic effects of the dipeptidyl peptidase-4 inhibitor linagliptin versus the sulphonylurea glimepiride in adults with type 2 diabetes (RENALIS): a pre-defined sub-study of a randomized, double-blind trial
Muskiet, Marcel H A; Tonneijck, Lennart; Smits, Mark M; Kramer, Mark H H; Ouwens, D Margriet; Hartmann, Bolette; Holst, Jens J; Danser, A H Jan; Joles, Jaap A; van Raalte, Daniël H
(2022) Diabetes, Obesity & Metabolism, volume 24, issue 1, pp. 115 - 124
(Article)
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
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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 (R E ; 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 FE Na . Change in glucagon was associated with change in R E (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 R E .
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Keywords: DPP-4 inhibitor, dipeptidyl peptidase-4, glomerular filtration rate, linagliptin, postrandial hyperfiltration, sulphonylurea, type 2 diabetes, Endocrinology, Internal Medicine, Endocrinology, Diabetes and Metabolism, Journal Article
ISSN: 1462-8902
Publisher: Wiley-Blackwell
Note: Funding Information: Funding for this investigator‐initiated study was provided by Boehringer Ingelheim. Funding information 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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