Postprandial renal hemodynamic effects of DPP-4 inhibitor linagliptin versus sulfonylurea glimepiride in adults with type 2 diabetes (RENALIS): a pre-defined sub-study of a randomized, double-blind trial

AIMS: To determine the effect of dipeptidyl-peptidase (DPP)-4-inhibitor linagliptin on postprandial glomerular hyperfiltration compared to the sulfonylurea glimepiride in adults with type 2 diabetes (T2DM).

MATERIALS AND METHODS: In this pre-defined sub-study within a randomized, double-blind, parallel-group, intervention-trial, overweight people with T2DM without renal-impairment were treated with once-daily linagliptin 5 mg (N = 10) or glimepiride 1 mg (N = 13) as add-on to metformin for 8 weeks. After a standardized liquid protein-rich meal, GFR and effective renal plasma flow were determined by inulin and para-aminohippuric acid clearance, respectively, based on timed urine-sampling. Intrarenal hemodynamics were estimated using Gomez'-equations. Glucoregulatory/vasoactive hormones, urinary-pH and fractional excretions (FE) of sodium, potassium and urea were measured.

RESULTS: Linagliptin compared to glimepiride increased postprandial filtration fraction (FF; mean-difference 2.1%; P = 0.016) and estimated glomerular hydraulic pressure (mean-difference 3.0 mmHg; P = 0.050), and tended to increase GFR (P = 0.08) and estimated efferent renal arteriolar resistance (RE ; P = 0.08) from baseline to Week-8. No differences in FE were noted. Glimepiride reduced HbA1c more than linagliptin (mean-difference - 0.40%; P = 0.004), 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 = 0.009) and time-averaged-mean glucagon (R = 0.782; P = 0.008), but not with changes in glucose, insulin, intact GLP-1, renin or FENa . Change in glucagon was associated with change in RE (R = 0.830; P = 0.003).

CONCLUSIONS: In contrast to our hypothesis, linagliptin compared to glimepiride does not reduce postprandial hyperfiltration, yet seems to increase FF after meal-ingestion by increasing blood pressure or RE . This article is protected by copyright. All rights reserved.