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Lorcaserin: New agent in the obesity armamentarium
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Lorcaserin is a novel agent that acts as an agonist at central serotonin subtype 2c, or 5HT2c, although the exact mechanism is not fully understood.
The weight-loss effects of lorcaserin (Belviq, Arena Pharmaceuticals) are believed to be due to agonism of central 5HT2c receptors leading to reduced caloric intake and increased satiety. Lorcaserin has been studied in three large clinical trials that included patients with diabetes.
BLOSSOM
The BLOSSOM trial included patients aged 18 to 65 years with a BMI between 30 kg/m2 and 45 kg/m2, or those with a BMI between 27 kg/m2 and 29.9 kg/m2 with at least one concomitant weight-related comorbidity, such as hypertension, dyslipidemia, cardiovascular disease, impaired glucose tolerance or obstructive sleep apnea. A total of 4,008 participants were randomly assigned to lorcaserin 10 mg once daily (n=801), lorcaserin 10 mg twice daily (n=1,602) or placebo (n=1,601) for 52 weeks. Nutritional and exercise counseling were included at each study visit. The mean baseline body weight and BMI were 100 kg and 36 kg/m2, respectively. The primary outcome was the proportion of patients who lost at least 5% or at least 10% of their baseline body weight; analysis was conducted using a modified-intention-to-treat (MITT) approach with the last observation carried forward (LOCF).
James R. Taylor
After 1 year of treatment, 47.2% of those assigned lorcaserin twice daily lost more than 5% of their baseline body weight compared with 40.2% of those assigned lorcaserin once daily and 25% of those assigned placebo (P<.0001 for both doses of lorcaserin vs. placebo). More than 10% weight loss was achieved by 22.6% of patients assigned lorcaserin twice daily, 17.4% assigned lorcaserin once daily and 9.7% assigned placebo (P<.001 for both doses vs. placebo). Absolute weight loss, calculated by least squares (LES) mean, were 5.8 kg, 4.7 kg and 2.9 kg for lorcaserin twice daily, lorcaserin once daily and placebo. Although systolic blood pressure, diastolic BP and heart rate decreased in all groups, the difference was not statistically significant.
BLOOM
The BLOOM study enrolled patients aged 18 to 65 years with a baseline BMI of 30 kg/m2 to 45 kg/m2 or a BMI of 27 kg/m2 to 45 kg/m2 with at least one concomitant weight-related comorbidity such as hypertension, CVD, dyslipidemia, IGT or obstructive sleep apnea. A total of 3,182 patients were randomly assigned to lorcaserin 10 mg twice daily (n=1,595) or placebo (n=1,587) for 52 weeks. At 52 weeks, those receiving placebo continued for an additional 52 weeks, whereas those receiving lorcaserin twice daily were randomly assigned in a 2:1 ratio to continue receiving lorcaserin or be switched to placebo. A total of 573 patients received lorcaserin for 2 years, 283 received lorcaserin for 1 year and placebo for 1 year, and 697 received placebo for 2 years; nutritional and exercise counseling was provided at each visit. At randomization, mean weight and BMI were 100 kg and 36 kg/m2, respectively.
The primary outcome — percent of patients who achieved more than 5% weight loss of baseline body weight after 52 weeks — occurred in 47.5% of those receiving lorcaserin compared with 20.3% receiving placebo (MITT population with LOCF, P<.001). The mean decrease in body weight (calculated using LES mean) was 5.8% (5.8 kg) for lorcaserin compared with 2.2% (2.2 kg) for placebo. After 104 weeks of treatment, more patients who continued lorcaserin were able to maintain weight loss of more than 5% compared with those who transitioned to placebo (67.9% vs. 50.3%, respectively; P<.001). Secondary outcomes, including percent achieving more than 10% weight loss (P<.001), reduction in waist circumference, BP reduction and BMI, improved with lorcaserin after 52 weeks of treatment.
BLOOM-DM
Finally, the BLOOM-DM study enrolled patients aged 18 to 65 years with a BMI of 27 kg/m2 to 45 kg/m2 and a diagnosis of type 2 diabetes with an HbA1c level between 7% and 10%; participants could only be receiving metformin, a sulfonylurea or both for the treatment of their type 2 diabetes. Patients were stratified by baseline type 2 diabetes treatment and randomly assigned to lorcaserin 10 mg twice daily (n=256), lorcaserin 10 mg once daily (n=95) or placebo (n=253) for 52 weeks; enrollment into the lorcaserin 10 mg once-daily group was stopped after 8 months due to slow enrollment. Patients received standardized nutritional and exercise counseling at each visit. At baseline, mean body weight was 104 kg and mean BMI was 36 kg/m2.
The primary outcome was the proportion of patients losing at least 5% and 10% of baseline body weight after 52 weeks of treatment; results were analyzed in the MITT population with the LOCF. Approximately 45% and 38% of the lorcaserin once-daily and twice-daily patients achieved at least 5% weight loss compared with only 16% in the placebo group (P<.001 for both doses compared with placebo).
More than 10% reduction in body weight was achieved by only 4.4% in the placebo group compared with 16.3% of those receiving lorcaserin twice daily and 18.1% of those receiving lorcaserin once daily (P<.001 for both doses compared with placebo). Absolute weight loss (using LES means) with lorcaserin twice daily was 4.7 kg, 5 kg with lorcaserin once daily and 1.6 kg with placebo. Treatment with lorcaserin also improved secondary outcomes, although the absolute changes in many of the secondary outcomes were minor and are of unknown clinical relevance.
Lorcaserin is approved at a dose of 10 mg twice daily in patients with a BMI >30 kg/m2 or a BMI >27 kg/m2 with at least one weight-related comorbidity such as hypertension, type 2 diabetes or dyslipidemia, in addition to a reduced calorie diet and increased physical activity. The most common adverse events with lorcaserin include headache, upper respiratory tract symptoms and infection, dizziness, nausea, constipation, fatigue and dry mouth.