Rimonabant appears to reduce risk factors for heart disease in obese people

A new drug could substantially reduce the bodyweight, waist circumference, and risk factors for heart disease in obese people, according to results of a randomised trial published in this week’s issue of The Lancet.

More than 50% of Europeans are currently classified as overweight and up to 20% clinically obese. Yearly, around a quarter of a million deaths in Europe and more than 2.5 million deaths worldwide are weight-related, with cardiovascular disease as the leading cause.

Luc Van Gaal (University Hospital Antwerp, Belgium) and colleagues undertook a trial (RIOEurope) involving 1507 people from Europe and the USA. Participants had a body mass index (BMI) of 30 kg/m2 or greater, or a BMI greater than 27 kg/m2 with abnormal blood fat levels, high blood pressure, or both. They were randomly assigned 5mg or 20mg of a drug called rimonabant, or a placebo once daily in addition to a calorie controlled diet. The treatment groups had similar characteristics. 920 patients (61%) completed the one-year follow-up; 379 in the rimonabant 5mg group, 363 in the rimonabant 20mg group and 178 in the placebo group.

Weight loss at 1 year was greater in patients treated with 5 mg or 20 mg of rimonabant compared with placebo. More than 67% of patients who completed treatment with 20mg of rimonabant achieved 5% or more weight loss, and 39% achieved 10 % or more weight loss. Patients on 20 mg of rimonabant had greater improvements than placebo in waist circumference (average reduction of 4 cm), and cardiovascular risk factors including cholesterol, insulin resistance and prevalence of metabolic syndrome. The pattern of weight loss seen with rimonabant was sustained for around 36-40 weeks. The most common side effects leading to study discontinuation were depressed mood disorders in all treatment groups; withdrawls due to nausea, vomiting, diarrhoea, headache, dizziness, and anxiety were more frequent in the rimonabant 20 mg group than in other groups. Serious adverse events did not occur more frequently in patients treated with the drug than in those on placebo.

Professor Van Gaal concludes: “In this study, treatment with rimonabant over 1 year led to sustained, clinically meaningful weight loss, reduction in waist circumference, and associated improvements in several cardiovascular and metabolic risk factors."

In an accompanying Comment Uberto Pagotto and Renato Pasquali (Sant Orsola-Malpighi General Hospital, Bologna, Italy) state: “These data, and those from the other ongoing clinical trials with rimonabant, might presumably help us to better tackle obesity and related metabolic and cardiovascular disease. When additional drugs are available, we will also have the possibility to individually target the therapeutic strategies according to phenotype characteristics and to the pathophysiological mechanism inducing the disease.”