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

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, doubleblind, 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 (R E ; P = .08) from baseline to week 8. No differences in FE were noted. Glimepiride reduced HbA1c more than linagliptin (mean difference À0.40%; 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).

Acute effects of linagliptin on intact and total glucagon‐like peptide‐1 and gastric inhibitory polypeptide levels in insulin‐dependent type 2 diabetes patients with and without moderate renal impairment

“…Another aspect of interest in this context appears to be postprandial renal hyperfiltration, which can be observed after the intake of a protein‐rich meal 37 . Since a recent study investigating the effects of linagliptin on postprandial hyperfiltration showed an increase in postprandial filtration fraction compared to glimepiride, 38 data on fasting and postprandial eGFR might have added interesting information on the effects of linagliptin on postprandial hyperfiltration. However, since the “test meal” did not contain any protein, potential effects of postprandial (hyper‐)filtration in the present study remain speculative.…”

Emerging role of antidiabetic drugs in cardiorenal protection

“…Postprandial glomerular hyperfiltration may be one of the renal risk factors in diabetic patients. Compared with glimepiride, linagliptin does not improve postprandial hemodynamics, and may even moderately induce postprandial glomerular hyperfiltration ( Muskiet et al, 2020 ; Muskiet et al, 2022 ).…”