Effect of Rimonabant on Glycemic Control in Insulin-Treated Type 2 Diabetes: The ARPEGGIO Trial

Abstract

OBJECTIVETo examine the efficacy and safety of rimonabant, a selective cannabinoid receptor type-1 antagonist, in patients with type 2 diabetes receiving insulin monotherapy.RESEARCH DESIGN AND METHODSPatients (n = 368; A1C ≥7%) were randomized to 20 mg/day rimonabant or placebo in this 48-week, double-blind, placebo-controlled multicenter trial. Change in baseline A1C to week 48 (primary outcome) and changes in body weight, waist circumference, and lipid levels (secondary outcomes) were assessed.RESULTSRimonabant significantly reduced baseline A1C versus placebo (−0.89 vs. −0.24%; P < 0.0001), and significantly greater improvements were observed in cardiometabolic risk factors. More rimonabant patients achieved >10% reduction in mean total daily insulin dose versus placebo (P = 0.0012), and fewer required rescue medication (P < 0.0001). Hypoglycemia, nausea, dizziness, anxiety, and depression were more frequent with rimonabant.CONCLUSIONSRimonabant improved glycemic control and cardiometabolic risk factors in patients with type 2 diabetes receiving insulin.

G1359A Polymorphism in the Cannabinoid Receptor-1 Gene is Associated with the Presence of Coronary Artery Disease in Patients with Type 2 Diabetes

“…More patients achieved greater than 10% reduction in mean total daily insulin dose in the rimonabant group than in the placebo group. 12 However, our results indicated that G1359A polymorphism was not associated with the presence of T2DM, which indicated that this polymorphism may not increase the susceptibility for T2DM. Further studies are needed to explain whether this polymorphism contribute to the risk for T2DM.…”

The role of endocannabinoids system in fatty liver disease and therapeutic potentials

“…The efficacy and safety of Rimonabant in weight reduction and improving metabolic syndrome parameters in different populations have been assessed in several trials. The four large ‘Rimonabant in obesity’ (RIO) studies involved over 6600 participants, composed of four separate trials: RIO North America,[60] RIO Europe,[61] RIO Diabetes[62] and RIO Lipids,[63] in addition to other randomized double-blind Rimonabant-placebo controlled trials, namely the Serenade,[64] Stradivarius,[65] Arpeggio[66] and Adagio-lipids studies. [67]…”

Rimonabant, a Cannabinoid Receptor Type 1 Inverse Agonist, Inhibits Hepatocyte Lipogenesis by Activating Liver Kinase B1 and AMP-Activated Protein Kinase Axis Downstream of Gαi/oInhibition

“…Rimonabant (SR141716A) is the first-in-class CB1 blocker for obesity treatment (Van Gaal et al, 2005). The data obtained from clinical trials suggest that rimonabant may have a beneficial effect against disrupted lipid metabolism in the liver (Després et al, 2005;Scheen et al, 2006;Hollander et al, 2010). However, the antisteatotic effect of rimonabant in hepatocytes and the molecular basis responsible for this action remain to be elucidated.…”