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J Clin Endocrinol Metab. 2012 Mar;97(3):819-27. doi: 10.1210/jc.2011-2486. Epub 2011 Dec 14.

Does rimonabant independently affect free fatty acid and glucose metabolism?

Author information

1
Endocrine Research Unit, Mayo Clinic, 200 1st Street SW, Rochester, Minnesota 55905, USA.

Abstract

CONTEXT:

Endocannabinoid receptor 1 blockade is proposed to improve metabolic complications of obesity via central and peripheral effects.

OBJECTIVE:

Our objective was to test whether rimonabant improves insulin regulation of free fatty acid and glucose metabolism after controlling for fat loss.

DESIGN:

This was a double-blind, placebo-controlled substudy of the visceral fat reduction assessed by computed tomography scan on rimonabant (VICTORIA) trial.

PARTICIPANTS AND SETTING:

Sixty-seven abdominally obese, metabolic syndrome volunteers age 35-70 yr participated at academic medical center general clinical research centers.

INTERVENTION:

Intervention included a 12-month lifestyle weight management program plus rimonabant 20 mg/d or placebo.

MAIN OUTCOME MEASURES:

Body composition and two-step euglycemic, hyperinsulinemic clamp before and after intervention were performed. Insulin sensitivity was assessed as insulin concentration needed to suppress by 50% palmitate concentration [IC50(palmitate)], flux [IC50(palmitate)f], and hepatic glucose output [IC50(HGO)] and as insulin-stimulated glucose disposal (Δ glucose disappearance per Δ insulin concentration--glucose slope).

RESULTS:

Body fat decreased by 4.5±2.9% (SD) in the rimonabant and 1.9±4.5% in the placebo group (P<0.005). The primary [improvement in IC50(palmitate) and IC50(palmitate)f] and secondary [improvement in IC50(HGO) and glucose slope] outcomes were not significantly different between the rimonabant and placebo groups. Post hoc analyses revealed that 1) changes in body mass index (BMI) and IC50(palmitate) were correlated (P=0.005) in the rimonabant group; this relationship was not significantly different from placebo when controlling for greater BMI loss (P=0.5); 2) insulin-regulated glucose disposal improved in both groups (P=0.002) and correlated with changes in BMI.

CONCLUSIONS:

Improvements observed in insulin regulation of free fatty acid and glucose metabolism with rimonabant treatment in humans was not greater than that predicted by weight loss alone.

PMID:
22170727
PMCID:
PMC3319222
DOI:
10.1210/jc.2011-2486
[Indexed for MEDLINE]
Free PMC Article

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