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

Abstract

Objective To assess the glucose-lowering efficacy and safety of rimonabant monotherapy in drug-naïve, 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-naïve 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 (Δ HbA_1c –0.51%; P = 0.0002), with a larger rimonabant effect in patients with baseline HbA_1c ≥8.5% (Δ HbA_1c –1.25%; P = 0.0009). Weight loss from baseline was –6.7 kg with rimonabant versus –2.8 kg with placebo (Δ 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-naïve T2DM patients. Further ongoing studies will better establish the benefit:risk profile of rimonabant and define its place in T2DM management.