Efficacy Of Lorcaserin Research Articles

An up-to-date evaluation of lorcaserin hydrochloride for the treatment of obesity

ABSTRACT Introduction: Obesity is a chronic disease caused by dysfunctional neurohormonal systems that result in excess weight, adiposopathy, and increased risk for many comorbidities including cardiovascular disease, type 2 diabetes, and certain types of cancer. Lorcaserin is a serotonergic agonist specific to the 5HT2C receptor that is FDA-approved for the long-term management of obesity in adults with BMI>30 kg/m2 or BMI>27 kg/m2 and at least one weight-related comorbidity. Areas covered: The authors review the pharmacodynamics and pharmacokinetic properties of lorcaserin alongside updates on serotonin’s mechanism of action in the central nervous system. The efficacy of lorcaserin in the management of obesity, its related comorbidities, and potential therapeutic applications are also discussed. Expert opinion: The future of obesity management requires a multimodal and personalized approach. The high medical complexity of patients warrants polypharmacotherapy to achieve their metabolic goals. Lorcaserin has proven efficacy and safety in the treatment of obesity and its weight-related comorbidities including type 2 diabetes, cardiovascular disease, and chronic kidney disease. New evidence elucidating its effects on dopaminergic pathways and on glucose homeostasis expands its prospective uses.

Cardiovascular Safety of Lorcaserin in Overweight or Obese Patients

BackgroundLorcaserin, a selective serotonin 2C receptor agonist that modulates appetite, has proven efficacy for weight management in overweight or obese patients. The cardiovascular safety and efficacy of lorcaserin are undefined.MethodsWe randomly assigned 12,000 overweight or obese patients with atherosclerotic cardiovascular disease or multiple cardiovascular risk factors to receive either lorcaserin (10 mg twice daily) or placebo. The primary safety outcome of major cardiovascular events (a composite of cardiovascular death, myocardial infarction, or stroke) was assessed at an interim analysis to exclude a noninferiority boundary of 1.4. If noninferiority was met, the primary cardiovascular efficacy outcome (a composite of major cardiovascular events, heart failure, hospitalization for unstable angina, or coronary revascularization [extended major cardiovascular events]) was assessed for superiority at the end of the trial.ResultsAt 1 year, weight loss of at least 5% had occurred in 1986 of 5135 patients (38.7%) in the lorcaserin group and in 883 of 5083 (17.4%) in the placebo group (odds ratio, 3.01; 95% confidence interval [CI], 2.74 to 3.30; P<0.001). Patients in the lorcaserin group had slightly better values with respect to cardiac risk factors (including blood pressure, heart rate, glycemic control, and lipids) than those in the placebo group. During a median follow-up of 3.3 years, the rate of the primary safety outcome was 2.0% per year in the lorcaserin group and 2.1% per year in the placebo group (hazard ratio, 0.99; 95% CI, 0.85 to 1.14; P<0.001 for noninferiority); the rate of extended major cardiovascular events was 4.1% per year and 4.2% per year, respectively (hazard ratio, 0.97; 95% CI, 0.87 to 1.07; P=0.55). Adverse events of special interest were uncommon, and the rates were generally similar in the two groups, except for a higher number of patients with serious hypoglycemia in the lorcaserin group (13 vs. 4, P=0.04).ConclusionsIn a high-risk population of overweight or obese patients, lorcaserin facilitated sustained weight loss without a higher rate of major cardiovascular events than that with placebo. (Funded by Eisai; CAMELLIA–TIMI 61 ClinicalTrials.gov number, NCT02019264.)

Abstract P456: Examining Framingham Coronary Heart Disease 10-year Risk Reduction in Individuals Treated With Lorcaserin, a Selective 5HT 2C Receptor Agonist for Weight Management

Introduction: Obesity contributes significantly to cardiovascular disease (CVD) risk and weight management is associated with CVD risk reduction. Lorcaserin, a selective 5HT 2C receptor agonist, is indicated as an adjunct to a reduced-calorie diet and increase physical activity for weight management in adults with obesity (BMI≥30) and overweight (BMI 27-29.9 and ≥1 weight-related comorbidity). This analysis used the Framingham 10-year CVD risk to examine the impact of lorcaserin treatment on CVD risk and risk reduction. Method: Pooled data from two randomized, double-blind studies (BLOOM &amp; BLOSSOM) investigating the efficacy of lorcaserin vs. placebo among non-diabetic patients with overweight or obesity, were used in this analysis. Framingham CVD risk was calculated for those whose lipid values were available at baseline and at one year. A Framingham CVD risk of &lt;5% was classified as low risk. Patients were stratified by cohort, lorcaserin (LOR) vs. placebo (PBO) and response at week 12 (≥5% weight loss vs. &lt; 5%) for calculating the 10-year CVD risk at one year. Logistic regression was used to adjust for baseline risk and determine if proportional differences in risk reduction were significant. Results: A total of 5,658 patients were evaluated, 51% treated with LOR. Among the LOR-treated patients, 43% achieved ≥5% weight loss at week 12 (compared to 19% treated with PBO). At one year, more patients in the LOR cohort had reduced CVD risk (from high to low risk, 21% vs. 15%, respectively). The regression analysis showed LOR-treated patients were 34% more likely to have low CVD risk (p&lt;0.001). Similarly, for patients who lost ≥5% baseline body weight at 12 weeks, more patients in the LOR cohort had reduced CVD risk (from high to low risk, 26% vs. 16% respectively) at one year. The regression showed LOR-treated patients were 23% more likely to have low CVD risk (p&lt;0.05). Conclusion: The analysis suggests that patients treated with LOR are more likely to have low CVD risk at one year than those treated with PBO. The effect is magnified if patients have ≥5% weight loss at 12 weeks.

Psychopathological Behaviour and Cognition in Morbid Obesity.

Obesity is a chronic condition with high prevalence and multifaceted aetiology, accompanied by an increased risk of morbidity and mortality. Obesity has several negative effects on the psychological status, and the severity of psychological disorders correlates with the degree of obesity. Aim of this review is to provide an overview of the literature concerning the psychological distress associated with severe obesity, which contributes to deterioration of the quality of life of affected patients. Dysfunctional eating behaviours and eating disorders, psychiatric comorbidity, cognition and quality of life will be discussed together with the most common drugs that can be employed to treat the various disorders in this peculiar clinical setting. The effects of bariatric surgery will be also reviewed. Obesity is often the result of pathological behaviours implemented in an eating disorder. Inconsistent results have been reported with regard to the effect of severe obesity on cognition, which recognize a multifaceted aetiology. Serotonergic agents play an important role in the management of patients with obesity and binge episodes, fluoxetine being currently a drug approved for this disorder. The efficacy of lorcaserin, a combination of bupropion and naltrexone, or antiepileptic medications (topiramate and zonisamide) has also been proposed. A neuroprotective role of leptin and oestrogen has been hypothesized. Bariatric surgery is a helpful treatment of morbid obese patients, with long-term favourable results on the psychopathological profile. Psychological, psychoeducational and psychopharmacological treatment can facilitate weight loss in morbid obese subjects with psychopathological comorbidities. A precise definition of the mechanisms affecting appetite, satiety and energy balance is expected to foster the development of new effective antiobesity drugs.

Safety and tolerability review of lorcaserin in clinical trials.

Lorcaserin is a novel selective serotonin 2C receptor agonist indicated by the US Food and Drug Administration for chronic weight management in adults with obesity or overweight with ≥1 comorbidity. The safety and efficacy of lorcaserin were established during two Phase III clinical trials in patients without diabetes (BLOOM and BLOSSOM) and one Phase III clinical trial in patients with type 2 diabetes (BLOOM-DM). Headache was the most common adverse event experienced by patients during all Phase III trials. Additional adverse events occurring in >5% of patients receiving lorcaserin included dizziness, fatigue, nausea, dry mouth and constipation in patients without diabetes, and hypoglycaemia, back pain, cough and fatigue in patients with diabetes. In a pooled analysis of echocardiographic data collected during the three lorcaserin Phase III trials, the incidence of FDA-defined valvulopathy was similar in patients taking lorcaserin and the placebo. Here, the safety profile of lorcaserin at the FDA-approved dose of 10 mg twice daily is reviewed using data from the lorcaserin Phase III programme, with a focus on theoretical adverse events commonly associated with agonists of the serotonin receptor family. Based on the lorcaserin Phase III clinical trial data, lorcaserin is safe and well tolerated in the indicated patient populations.

Safety and Efficacy of Lorcaserin: A Combined Analysis of the BLOOM and BLOSSOM Trials

Background: Lorcaserin, a novel selective 5-HT2C receptor agonist, is approved by the US Food and Drug Administration (FDA) for weight management in combination with lifestyle modification for adults with obesity and adults with overweight and ≥ 1 weight-related comorbid condition. The safety and effectiveness of lorcaserin in adult patients without type 2 diabetes mellitus was established based on 2 phase III clinical trials of similar design: Behavioral Modification and Lorcaserin for Overweight and Obesity Management (BLOOM) and Behavioral Modification and Lorcaserin Second Study for Obesity Management (BLOSSOM). This report presents a prespecified analysis of pooled data from these trials. Methods: Co-primary end points in this analysis include the proportion of patients with a reduction in baseline body weight of ≥ 5% and ≥ 10%, and a change in weight from baseline. Key secondary end points include changes from baseline values in lipid parameters, quality-of-life measures, glycemic indicators, and vital signs. Results: At week 52, more than twice as many lorcaserin-treated patients achieved a weight loss of ≥ 5% compared with placebo (lorcaserin, 47.1%; placebo, 22.6%), and lorcaserin-treated patients lost significantly more body weight (lorcaserin, −5.8%; placebo, −2.5%). A significantly greater proportion of lorcaserin-treated patients achieved a weight loss of ≥ 10% (lorcaserin, 22.4%; placebo, 8.7%). There were statistically significant improvements in lipid parameters, glycemic indicators, quality-of-life measures, and vital signs in the lorcaserin group compared with placebo. The most common adverse events associated with lorcaserin treatment were headache, upper respiratory tract infection, and nasopharyngitis. Lorcaserin-treated patients had a rate of FDA-defined valvulopathy similar to placebo. Conclusions: This pooled analysis of the phase III BLOOM and BLOSSOM trials shows that lorcaserin 10 mg twice daily, in combination with diet and exercise, is safe and tolerable, and is associated with statistically significant weight loss and clinically relevant improvements in cardiometabolic parameters.

The Safety and Efficacy of Lorcaserin in the Management of Obesity

Lorcaserin represents a new serotonergic medication used as an adjunct to a reduced-calorie diet and increased physical activity treatment plan for chronic weight management in adult patients with an initial body mass index ≥ 30 kg/m2 or in adult patients with an initial body mass index ≥ 27 kg/m2 who have ≥ 1 comorbid condition associated with weight (eg, hypertension, dyslipidemia, or type 2 diabetes mellitus). In 2012, lorcaserin became the first obesity treatment medication to gain US Food and Drug Administration (FDA) approval since 1999. Lorcaserin is a centrally acting, selective serotonin C (5-HT2C) receptor full agonist that is associated with increased satiety and decreased food consumption in patients. The selectivity of lorcaserin for 5-HT2C receptors should reduce patient risk for the serious adverse complications that are associated with nonselective 5-HT agonist therapies, such as cardiac valvulopathy and pulmonary hypertension. The safety and efficacy of lorcaserin (10 mg twice daily) for ≥ 52 weeks has been evaluated in 3 separate Phase 3 trials. The primary outcome of patient weight loss in the 3 trials satisfied the FDA categorical benchmark but patient outcomes in the trials failed to achieve the FDA mean benchmark of patient weight loss. Secondary patient outcomes after lorcaserin therapy were favorable. Lorcaserin appears to be well tolerated in patients and the most common adverse events reported did not include serious complications. The incidence of FDA-defined valvulopathy in patients after 1 year of treatment was low and nonsignificant, but the statistical analysis of this safety endpoint was limited due to the small size of the study populations and high patient dropout rates. Continued post-marketing surveillance of patients taking lorcaserin is warranted.

Lorcaserin

Lorcaserin