What is the clinical evidence from this study?

Study design: RCT. Population: Healthy overweight (n=10). Intervention: Exenatide vs. Placebo (isotonic 0.9% saline). Primary outcome: Change in glomerular filtration rate (GFR) (MD 18 ml/min/1.73m2, p=0.021).

November 2, 2015Open Access

Acute renal haemodynamic effects of glucagon‐like peptide‐1 receptor agonist exenatide in healthy overweight men

Key Result

Exenatide infusion acutely increased glomerular filtration rate by 20% (mean 18 ml/min/1.73m2) compared to placebo in healthy overweight men.

Study Design

Type

RCT (n=10)

Blinding

Open-label

Randomization

Not specified

Multicenter

Structured PICO

Does intravenous exenatide acutely increase glomerular filtration rate and alter renal hemodynamics in healthy overweight men?

Population

10 healthy overweight men aged 18-30 years underwent acute intravenous administration of exenatide and placebo to evaluate renal haemodynamic effects.

Intervention

Intravenous exenatide (10 μg diluted, 50 ng/min for 30 min, then 25 ng/min) alone and combined with intravenous L-NMMA (5 mg/kg loading, then 50 μg/kg/min).

Comparator

Intravenous placebo (isotonic 0.9% saline).

Outcome

Change in glomerular filtration rate (GFR) after i.v. exenatide administration compared with isotonic 0.9% saline (placebo).surrogate

Acute intravenous administration of the GLP-1 receptor agonist exenatide increases glomerular filtration rate and effective renal plasma flow in healthy overweight men, partially via nitric oxide-dependent mechanisms.

Main Result

Mean Difference: 18

Absolute Event Rate: 114% vs 97%

p-value: p=0.021

Limitations

Small sample size
Study population is not the target population for GLP-1 receptor agonist treatment
Intervention conditions were performed in a sequential fashion, unable to exclude time-dependent effects
Estimation of glomerular characteristics with the Gomez formulae requires assumptions

Abstract

AIMS: To determine the acute effect of glucagon-like peptide-1 (GLP-1) receptor agonist exenatide and the involvement of nitric oxide (NO) on renal haemodynamics and tubular function, in healthy overweight men. METHODS: Renal haemodynamics and tubular electrolyte handling were measured in 10 healthy overweight men (aged 20-27 years; BMI 26-31 kg/m(2)) during intravenous administration of placebo (saline 0.9%), exenatide, and exenatide combined with the NO-synthase inhibitor L-N(G)-monomethyl arginine (L-NMMA). Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were determined by inulin and para-aminohippurate clearance techniques, respectively, based on timed urine sampling. Glomerular hydrostatic pressure and vascular resistance of afferent and efferent renal arterioles were calculated using the Gomez formulae. Urinary electrolytes, osmolality and pH were also measured. RESULTS: GFR increased by a mean of 18 ± 20 (+20%; p = 0.021) and ERPF increased by a median (interquartile range) of 68 (26; 197) ml/min/1.73 m(2) (+14%; p = 0.015) during exenatide infusion versus placebo. During L-NMMA infusion, exenatide increased GFR by mean 8 ± 12 ml/min/1.73 m(2) (+9%; p = 0.049). Exenatide increased estimated glomerular pressure by +6% (p = 0.015) and reduced afferent renal vascular resistance by -33% (p = 0.038), whereas these effects were blunted during L-NMMA infusion. Exenatide increased absolute and fractional sodium excretion, urinary osmolality and urinary pH. The tubular effects of exenatide were not altered by concomitant L-NMMA infusion. CONCLUSIONS: Exenatide infusion in healthy overweight men acutely increases GFR, ERPF and glomerular pressure, probably by reducing afferent renal vascular resistance, and at least partially in an NO-dependent manner. As baseline renal haemodynamics in patients with type 2 diabetes differ from those in healthy individuals, clinical studies on the renal effects of GLP-1 receptor agonists are warranted.

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