SERENADE: The Study Evaluating Rimonabant Efficacy in Drug-Naive Diabetic Patients 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

OBJECTIVE - The purpose of this study was to assess the glucose-lowering efficacy and safety of rimonabant monotherapy in drug-naive type 2 diabetic patients. RESEARCH DESIGN AND METHODS - The Study Evaluating Rimonabant Efficacy in Drug-Naive Diabetic Patients (SERENADE) was a 6-month, randomized, double-blind, placebo-controlled trial of 20 mg/day rimonabant in drug-naive patients with type 2 diabetes (A1C 7-10%). The primary end point was A1C change from baseline; secondary end points included body weight, waist circumference, and lipid profile changes. RESULTS - A total of 281, patients were randomly assigned 278 were exposed to treatment and 236 (84.9%) completed the study. Baseline A1C (7.9%) was reduced by -0-8% with rimonabant versus -0.3% with placebo (Delta A1C -0.51%; P = 0.0002), with a larger rimonabant effect in patients with baseline A1C >= 8.5% (Delta A1C - 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 were 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 type 2 diabetic patients. Further ongoing studies will better establish the benefit-to-risk profile of rimonabant and define its place in type 2 diabetes management.