Rimonabant Maintains Weight Loss Out to 2 Years, Improves Lipid Profile

By Wayne Kuznar

New Orleans—Overweight or obese patients are at increased risk for the metabolic syndrome and cardiovascular disease. The investigational weight-loss agent rimonabant (Acomplia) can help patients maintain their weight loss for the long-term and improve their lipid profiles, according to new data released at the American Heart Association’s 2004 Scientific Sessions.

“Patients treated with 20 mg of rimonabant for 2years experienced a reduction in body weight and in waist circumference, demonstrating a significant reduction in abdominal fat, a key marker for cardiovascular disease,” said Xavier Pi-Sunyer, MD, chief, division of endocrinology, St. Luke’s-Roosevelt Hospital Center, Columbia University, New York, and lead investigator of a large, phase 3 North American study.

Rimonabant, 5 or 20 mg/day, was compared with placebo in 3040 patients with a body mass index (BMI) ≥30 kg/m² or with a BMI >27 kg/m² and a comorbidity. All patients were prescribed mildly hypocaloric diet (ie, reduced caloric intake by 600 kcal/day).

Patients were randomized to 1 of the 3 treatment groups for an initial 52 weeks of double-blind treatment. At the end of 1 year, those in the rimonabant groups were rerandomized to either the same dose of rimonabant or to placebo, for another 52 weeks.

At 1 year, weight loss was: 2.8 kg with placebo, 4.4 kg with 5-mg rimonabant (P = .001), and 8.7 kg with 20-mg rimonabant (P <.001 vs placebo). Among the patients rerandomized from rimonabant, those assigned to placebo regained weight they had lost in year 1, whereas those rerandomized to 20 mg of rimonabant maintained their weight loss (weight change from baseline: —7.4 kg).

At 1 year, waist circumference was reduced by 3.9 cm in the placebo-receiving patients, compared with 4.7-cm reduction with 5-mg rimonabant and 8.2-cm reduction with the 20-mg dose of rimonabant (P <.001 vs placebo). These differences were maintained at the 2-year follow-up.

Of patients receiving the 20-dose of the active drug for 2 years, 62.5% lost >5% of their initial body weight and 32.8% lost >10% of their initial body weight, said Dr Pi-Sunyer.

Furthermore, during the 2-year period, patients treated with 20 mg/day “achieved a significant increase in high-density lipoprotein cholesterol, a reduction in triglycerides, and an improvement in insulin sensitivity,” Dr Pi-Sunyer said (Table).

At 2 years, the percentage of patients with serious adverse events or discontinuations due to adverse events was not different between the 3 groups, and no differences were evident in depression scores.

Table: Metabolic changes at end of 2 years: rimonabant versus placebo

Placebo Rimonabant, 5 mg Rimonabant, 20 mg

(%) (%) (%)

HDL 13.8 15.6¹ 24.5¹

TGY 1.6 5.9² 9.9²

NOTE:At baseline, 34.8% of those randomized to rimonabant, 20 mg, met diagnostic criteria for the metabolic syndrome. At end of 2 years, it was reduced to 22.5% (P <.001).

1. P <.001 vs placebo.

2. P <.05 vs placebo.

HDL = high-density lipoprotein; TGY = triglycerides.