Acute renal effects of the GLP-1 receptor agonist exenatide in overweight type 2 diabetes patients: a randomised, double-blind, placebo-controlled trial

Aims/hypothesis This study aimed to investigate the acute renal effects of the glucagon-like peptide-1 receptor agonist (GLP-1RA) exenatide in type 2 diabetes patients. Methods We included overweight (BMI 25–40 kg/m 2 ) men and postmenopausal women, aged 35–75 years with type 2 diabetes (HbA 1c 48–75 mmol/mol; 6.5–9.0%) and estimated GFR ≥ 60 ml min −1 1.73 m −2 . Exenatide or placebo (NaCl solution, 154 mmol/l) was administrated intravenously in an acute, randomised, double-blind, placebo-controlled trial conducted at the Diabetes Center VU University Medical Center (VUMC). GFR (primary endpoint) and effective renal plasma flow (ERPF) were determined by inulin and para-aminohippurate clearance, respectively, based on timed urine sampling. Filtration fraction (FF) and effective renal vascular resistance (ERVR) were calculated, and glomerular hydrostatic pressure (P GLO ) and vascular resistance of the afferent (R A ) and efferent (R E ) renal arteriole were estimated. Tubular function was assessed by absolute and fractional excretion of sodium (FE Na ), potassium (FE K ) and urea (FE U ), in addition to urine osmolality, pH and free water clearance. Renal damage markers, BP and plasma glucose were also determined. Results Of the 57 patients randomised by computer, 52 were included in the final analyses. Exenatide ( n = 24) did not affect GFR (mean difference +2 ± 3 ml min −1 1.73 m −2 , p = 0.489), ERPF, FF, ERVR or P GLO , compared with placebo ( n = 28). Exenatide increased R A ( p