Rupinderjeet Kaur, Paramdeep Singh, Amarpreet Kaur, Devinder S Mahajan, Harharpreet Kaur

Journal of Pharmaceutical Negative Results 2013 4(1):46-53

The objectives of this study were to study the total and differential effect of Rimonabant on weight parameters, lipid profile, glycemic profile, and blood pressure and to evaluate its safety profile in obese population of Punjab. Materials and Methods: This was a randomized open controlled study, carried out on 100 subjects that included Punjabi adults (18-70 years) who were obese or overweight (with associated risk factors) according to Asia pacific guidelines. Treatment group (n = 50) was given Rimonabant 20 mg once-daily, and control group (n = 50) was given placebo for 12 weeks. Alterations in weight and lipid parameters, Fasting blood sugar (FBS), and blood pressure were recorded. Psychiatric adverse events were monitored by HADS score. Analysis was done using SPSS software. Results: Statistically significant difference was observed in two groups in reduction in weight, waist circumference, body mass index. Overall reduction in number of patients in the obese category was 20% in group 1 and 6.25% in group 2. In lipid parameters, significant changes were observed in triglycerides (TG), HDL cholesterol, and total cholesterol: HDL ratio (P < 0.001). No significant change was observed for LDL cholesterol and total cholesterol. Effect on Fasting Blood Sugar (FBS) was also significant. Moderate decrease in systolic blood pressure and no significant change was observed in diastolic blood pressure. Using multivariate regression model, Rimonabant was found to have weight-loss independent effect on lipid parameters with triglycerides having the maximum percentage difference between regression coefficients. No significant correlation was observed between changes in lipid parameters and weight loss. Amongst the lipids, changes in triglycerides and HDL cholesterol correlated best. Decrease in FBS correlated with weight loss but not to lipid parameters. Adverse event profile was comparable in both groups. Depressive symptoms were noted in 3 subjects in treatment group with 1 requiring termination of treatment. Frequency of anxiety symptoms was same in both groups with none showing tendency towards suicide. Conclusions: This is the first study of Rimonabant on Punjabi population and reports the depressive adverse events to be occurring in low frequency and of mild intensity in this group. Thus, it provides a clue to the need for further studies of cannabinoid receptor antagonists on larger samples in such ethnically predisposed populations to reevaluate the safety profile and its genetic correlation. It also suggests need for further research on differential effect of antagonism of cannabinoid receptors in CNS and adipose tissue and its use to produce drug that targets metabolic derangements by selective action on adipose tissue receptors.