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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, 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 .

SUBMITTER: Muskiet MHA 

PROVIDER: S-EPMC9293357 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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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.

Muskiet Marcel H A MHA   Tonneijck Lennart L   Smits Mark M MM   Kramer Mark H H MHH   Ouwens D Margriet DM   Hartmann Bolette B   Holst Jens J JJ   Danser A H Jan AHJ   Joles Jaap A JA   van Raalte Daniël H DH  

Diabetes, obesity & metabolism 20211006 1


<h4>Aim</h4>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).<h4>Materials and methods</h4>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 metform  ...[more]

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