The SERENADE Trial: Effects of Monotherapy with Rimonabant, the First Selective CB1 Receptor Antagonist, on Glycemic Control, Body Weight and Lipid Profile in Drug-naive Type 2 Diabetes.

Author(s): Rosenstock J, Hollander P, Chevalier S, Iranmanesh A, for the SERENADE study group

Affiliation(s): Dallas Diabetes and Endocrine Center, TX, USA.

Publication date & source: 2008-08-04, Diabetes Care., [Epub ahead of print]

Publication type:

Objective To assess the glucose-lowering efficacy and safety of rimonabant monotherapy in drug-naive, type 2 diabetes (T2DM) patients. Research design and methods SERENADE was a 6-month, randomized, double-blind, placebo-controlled trial of rimonabant 20 mg/day in drug-naive patients with T2DM (HbA(1c) 7-10%). Primary endpoint was HbA(1c) change from baseline; secondary endpoints included body weight, waist circumference and lipid profile changes. Results 281 patients were randomized, 278 were exposed to treatment, and 236 (84.9%) completed the study. Baseline HbA(1c) (7.9%) was reduced by -0.8% with rimonabant versus -0.3% with placebo (Delta HbA(1c) -0.51%; P = 0.0002), with a larger rimonabant effect in patients with baseline HbA(1c) >/=8.5% (Delta HbA(1c) -1.25%; P = 0.0009). Weight loss from baseline was -6.7 kg with rimonabant versus -2.8 kg with placebo (Delta weight -3.8 kg; P < 0.0001). Rimonabant induced improvements from baseline in waist circumference (-6 vs. -2 cm; P < 0.0001), fasting plasma glucose (-0.9 vs. -0.1 mmol/L; P = 0.0012), triglycerides (-16.3% vs. +4.4%; P = 0.0031) and HDL-cholesterol (+10.1% vs. +3.2%; P < 0.0001). Adverse events of interest that occurred more frequently with rimonabant versus placebo: dizziness (10.9% vs. 2.1%), nausea (8.7% vs. 3.6%), anxiety (5.8% vs. 3.6%), depressed mood (5.8% vs. 0.7%) and paresthesia (2.9% vs.1.4%). Conclusions Rimonabant monotherapy resulted in meaningful improvements in glycemic control, body weight and lipid profile in drug-naive T2DM patients. Further ongoing studies will better establish the benefit:risk profile of rimonabant and define its place in T2DM management.