TY - JOUR
T1 - Postprandial renal haemodynamic effects of the dipeptidyl peptidase-4 inhibitor linagliptin versus the sulphonylurea glimepiride in adults with type 2 diabetes (RENALIS)
T2 - A predefined substudy of a randomized, double-blind trial
AU - Muskiet, Marcel H. A.
AU - Tonneijck, Lennart
AU - Smits, Mark M.
AU - Kramer, Mark H. H.
AU - Ouwens, D. Margriet
AU - Hartmann, Bolette
AU - Holst, Jens J.
AU - Danser, A. H. Jan
AU - Joles, Jaap A.
AU - van Raalte, Daniël H.
N1 - 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.
PY - 2022/1
Y1 - 2022/1
N2 - 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.
AB - 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.
KW - DPP-4 inhibitor
KW - dipeptidyl peptidase-4
KW - glomerular filtration rate
KW - linagliptin
KW - postrandial hyperfiltration
KW - sulphonylurea
KW - type 2 diabetes
UR - http://www.scopus.com/inward/record.url?scp=85116479294&partnerID=8YFLogxK
U2 - https://doi.org/10.1111/dom.14557
DO - https://doi.org/10.1111/dom.14557
M3 - Article
C2 - 34580975
SN - 1462-8902
VL - 24
SP - 115
EP - 124
JO - Diabetes, Obesity and Metabolism
JF - Diabetes, Obesity and Metabolism
IS - 1
ER -