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

作者：Tonneijck Lennart; Smits Mark M; Muskiet Marcel H A; Hoekstra Trynke; Kramer Mark H H; Danser A H Jan; Diamant Michaela; Joles Jaap A; van Raalte Daniel H

来源：Diabetologia, 2016, 59(7): 1412-1421.

DOI：10.1007/s00125-016-3938-z

• Diabetes
• Exenatide
• Glomerular filtration rate
• Glomerular hyperfiltration
• GLP-1 receptor agonist
• Glucagon-like peptide-1
• Renal function
• Renal haemodynamics
• Type 2 diabetes

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 a parts per thousand yenaEuro parts per thousand 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 (FENa), potassium (FEK) and urea (FEU), 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 < 0.05), but did not change R-E. Exenatide increased FENa, FEK, urine osmolality and pH, while FEU, urinary flow and free water clearance were decreased (all p < 0.05). Osmolar clearance and renal damage makers were not affected. Diastolic BP and mean arterial pressure increased by 3 +/- 1 and 6 +/- 2 mmHg, respectively, whereas plasma glucose decreased by 1.4 +/- 0.1 mmol/l (all p < 0.05).
Conclusions/interpretation Exenatide infusion does not acutely affect renal haemodynamics in overweight type 2 diabetes patients at normal filtration levels. Furthermore, acute GLP-1RA administration increases proximal sodium excretion in these patients.

• 出版日期2016-7