A One-Year Randomized Trial of Lorcaserin for Weight Loss in Obese and Overweight Adults: The BLOSSOM Trial
ABSTRACT Lorcaserin is a novel selective agonist of the serotonin 2C receptor.
Our objective was to evaluate the effects of lorcaserin on body weight, cardiovascular risk factors, and safety in obese and overweight patients.
This randomized, placebo-controlled, double-blind, parallel arm trial took place at 97 U.S. research centers.
Patients included 4008 patients, aged 18-65 yr, with a body mass index between 30 and 45 kg/m(2) or between 27 and 29.9 kg/m(2) with an obesity-related comorbid condition.
Patients were randomly assigned in a 2:1:2 ratio to receive lorcaserin 10 mg twice daily (BID), lorcaserin 10 mg once daily (QD), or placebo. All patients received diet and exercise counseling.
The ordered primary endpoints were proportion of patients achieving at least 5% reduction in body weight, mean change in body weight, and proportion of patients achieving at least 10% reduction in body weight at 1 yr. Serial echocardiograms monitored heart valve function.
Significantly more patients treated with lorcaserin 10 mg BID and QD lost at least 5% of baseline body weight (47.2 and 40.2%, respectively) as compared with placebo (25.0%, P < 0.001 vs. lorcaserin BID). Least squares mean (95% confidence interval) weight loss with lorcaserin BID and QD was 5.8% (5.5-6.2%) and 4.7% (4.3-5.2%), respectively, compared with 2.8% (2.5-3.2%) with placebo (P < 0.001 vs. lorcaserin BID; least squares mean difference, 3.0%). Weight loss of at least 10% was achieved by 22.6 and 17.4% of patients receiving lorcaserin 10 mg BID and QD, respectively, and 9.7% of patients in the placebo group (P < 0.001 vs. lorcaserin BID). Headache, nausea, and dizziness were the most common lorcaserin-related adverse events. U.S. Food and Drug Administration-defined echocardiographic valvulopathy occurred in 2.0% of patients on placebo and 2.0% on lorcaserin 10 mg BID.
Lorcaserin administered in conjunction with a lifestyle modification program was associated with dose-dependent weight loss that was significantly greater than with placebo.
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ABSTRACT: The 5-HT2C receptor agonist lorcaserin (Belviq®) has been Food and Drug Administration (FDA) approved for the treatment of obesity. The present study is a back translational investigation into the effect of 28-day lorcaserin treatment in a diet-induced obesity (DIO) model using male, Sprague–Dawley rats. An assessment of drug effect on efficacy and multiple safety endpoints including cardiac function was undertaken. Lorcaserin (1–2 mg/kg SC b.i.d.) significantly reduced percentage body weight gain compared to vehicle-treated controls (VEH: 10.6 ± 0.4%; LOR 1: 7.6 ± 1.2%; LOR 2: 5.4 ± 0.6%). Measurement of body composition using quantitative magnetic resonance (QMR) imaging indicated this change was due to the selective reduction in body fat mass. Modest effects on food intake were recorded. At the completion of the treatment phase, echocardiography revealed no evidence for valvulopathy, that is, no aortic or mitral valve regurgitation. The pharmacokinetics of the present treatment regimen was determined over a 7-day treatment period; plasma Cmin and Cmax were in the range 13–160 ng/mL (1 mg/kg b.i.d.) and 34–264 ng/mL (2 mg/kg b.i.d.) with no evidence for drug accumulation. In sum, these studies show an effect of lorcaserin in the DIO model, that in the context of the primary endpoint measure of % body weight change was similar to that reported clinically (i.e., 3.0–5.2% vs. 3.2%). The present studies highlight the translational value of obesity models such as DIO, and suggest that assuming consideration is paid to nonspecific drug effects such as malaise, the DIO model has reasonable forward translational value to help predict clinical outcomes of a new chemical entity.02/2015; 3(1). DOI:10.1002/prp2.84
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ABSTRACT: ABSTRACT Background: Visceral adiposity has been linked to higher rates of cardiometabolic risk than other types of adiposity. Waist circumference (WC) is the best anthropomorphic surrogate of visceral adiposity. Reductions in central adiposity may decrease cardiovascular risk. Animal studies have demonstrated that L-arginine reduces visceral adiposity and fat mass. The primary aim of our study was to assess the efficacy of L-arginine for reducing central adiposity in nondiabetic obese subjects. Secondary aims were to assess the efficacy of L-arginine for decreasing body mass index (BMI), waist-to-hip ratio (WHR), and weight. Materials and Methods: Female subjects (n = 20) were included if they: were ≥ 18 years and ≤ 40 years of age, had a BMI of ≥ 30 and ≤ 40 kg/m(2), had a WC ≥ 89 cm. Subjects received 3 g of L-arginine three times a day for 12 weeks and were counseled on lifestyle modification. Results: Overall, L-arginine was well tolerated with no clinically significant adverse events. Serum L-arginine levels were significantly increased from baseline at both 6 and 12 weeks (p < .05). WC (mean ± SD) decreased from 115.6 ± 12.7 cm at baseline to 109.2 ± 11.7 cm at 12 weeks (p = .0004). Weight (mean ± SD) decreased from 98.6 ± 19.7 kg at baseline to 95.7 ± 18.6 kg at 12 weeks (p = .015). Significant reductions from baseline were also observed in BMI and WHR. Conclusions: L-Arginine may be effective at reducing central adiposity in obese patients.Journal of Dietary Supplements 01/2014; 11(1). DOI:10.3109/19390211.2013.859216
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ABSTRACT: Moderate weight loss (>5%), which has been associated with improvements in glycemic parameters in patients with dysglycemia, also reduces the presence of other comorbidities, including dyslipidemia and hypertension, culminating in a reduced risk of cardiovascular disease. Lifestyle changes are the recommended preliminary approach to weight loss, with an initial weight-loss goal of 10% of body weight achieved over 6 months at a rate of 1-2 pounds per week selected as an appropriate target to decrease the severity of obesity-related risk factors. Implementing and maintaining the lifestyle changes associated with weight loss can, however, be challenging for many patients. Therefore, additional interventions sometimes may be necessary. Bariatric surgery can also be a highly effective option for weight loss and comorbidity reduction, but surgery carries considerable risks and is still applicable only to selected patients with type 2 diabetes. Thus, attention is turning to the use of weight-loss medications, including 2 recently approved compounds: twice-daily lorcaserin and a once-daily combination of phentermine and topiramate extended-release, both shown to be safe and effective therapies in the management of obesity in patients with type 2 diabetes.Journal of diabetes and its complications 05/2013; 27(5). DOI:10.1016/j.jdiacomp.2013.04.011 · 1.93 Impact Factor