lorcaserin and Cardiovascular-Diseases

Lorcaserin is a selective serotonin 2c receptor agonist approved as an anti-obesity agent. The additional cardiometabolic benefits associated with lorcaserin have not been conclusively established. The aim of the systematic review and meta-analysis is to examine the effects of lorcaserin on blood pressure, heart rate and other metabolic parameters in overweight and obese patients from randomized controlled clinical trials (RCTs).. A literature search was conducted on PubMed, EMBASE and Cochrane Central using the search terms 'lorcaserin' and 'randomized controlled trials' without language restrictions. RCTs with a follow-up period of at least 24 weeks were included in the meta-analysis.. Six studies with 9452 patients in the lorcaserin group and 9392 patients in the placebo group were included. Compared with placebo, lorcaserin not only reduced weight, BMI and waist circumference but also improved SBP, DBP, heart rate, LDL, triglycerides, fasting plasma glucose and HbA1c. Our findings suggest that lorcaserin has trivial though consistent and favourable effects on blood pressure, heart rate and metabolic syndrome.. Lorcaserin improved all cardiometabolic parameters modestly in addition to its weight loss effect in overweight and obese patients. More research is needed to determine its long-term cardiovascular benefits.

Topics: Benzazepines; Blood Pressure; Cardiovascular Diseases; Humans; Obesity; Overweight; Randomized Controlled Trials as Topic; Risk Factors; Weight Loss

Obesity is a growing health problem that has numerous comorbidities, including cardiovascular disease (CVD). The multi-disciplinary treatment of obesity now includes the use of pharmacotherapy. When treating patients with obesity and CVD, certain medications may be more appropriate than others.. Herein, the authors review the most commonly used FDA approved medications for the treatment of obesity, describing their mechanism of action, and the efficacy and safety of the medications as seen in recent studies, particularly in patients with CVD.. In the population of patients with obesity and CVD, the medications orlistat, lorcaserin and liraglutide are considered the most appropriate options for their treatment, in terms of safety. Sympathomimetic medications, such as phentermine, should be avoided in this group. The recent CAMELLIA-TIMI 61 trial supports the safety of lorcaserin in patients with CVD. Until there are more studies, it is reasonable to extrapolate the findings of the LEADER trial, which found improved CV outcomes in subjects with type 2 diabetes taking liraglutide, to the population of nondiabetic patients being treated for obesity. Further cardiovascular outcomes trials (CVOT) are needed to assess the safety of other pharmacotherapeutic options for weight loss.

Topics: Anti-Obesity Agents; Benzazepines; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Humans; Liraglutide; Obesity; Orlistat; Phentermine; Weight Loss

Obesity is a major correlate of cardiovascular disease. Weight loss improves cardiovascular risk factors and has the potential to improve outcomes. Two drugs, phentermine plus topiramate and lorcaserin, have recently been approved by the US Food and Drug Administration for the indication of obesity; a third, bupropion plus naltrexone, is under consideration for approval. In clinical trials, these drugs cause weight loss and improve glucose tolerance, lipid profile, and, with the exception of bupropion plus naltrexone, blood pressure. However, their effect on cardiovascular outcomes is unknown. In defining appropriate roles for these drugs in preventive cardiology, it is important to remember the checkered history of drugs for obesity. New weight-loss drugs share the serotonergic and sympathomimetic mechanisms that proved harmful in the cases of Fen-Phen and sibutramine, respectively, albeit with significant differences. Given these risks, randomized cardiovascular outcomes trials are needed to establish the safety, and potential benefit, of these drugs. This review will discuss the history of pharmacotherapy for obesity, existing efficacy and safety data for the novel weight-loss drugs, and issues in the design of postapproval clinical trials.

Topics: Anti-Obesity Agents; Benzazepines; Bupropion; Cardiovascular Diseases; Clinical Trials as Topic; Drug Combinations; Fructose; Heart; Humans; Naltrexone; Obesity; Phentermine; Topiramate

The incidence of obesity and its associated comorbidities have significantly increased over the years with adverse health and financial consequences for society. Lifestyle changes are essential for the prevention and treatment of obesity but their benefit appears limited as inadequate and nonsustained weight loss results have been reported. Pharmacotherapy is frequently advocated as part of a weight loss strategy. In this review, we will discuss the antiobesity drugs with Food and Drug Administration approval and their cardiovascular implications.. Orlistat (Xenical) remains the single monotherapy that has approval in Europe. Topiramate (Topamax) and phentermine have long been approved in the United States, whereas lorcaserin and the extended release combination of phentermine with topiramate have recently gained approval. The development of single peptides targeting gut hormones or other host signals related to obesity may represent promising therapeutic options.. Despite the recent failures of a number of antiobesity drugs, the pharmacotherapy of obesity is progressing rapidly. Treating the obese cardiovascular patient has proven challenging. Efficacy, safety and the sustainability of weight loss are key areas of focus in drug development strategies.

Topics: Anti-Obesity Agents; Benzazepines; Cardiovascular Diseases; Fructose; Humans; Lactones; Obesity; Orlistat; Phentermine; Topiramate

Obesity is a chronic disease with a high prevalence in both developed and developing countries. Effective management of this worldwide epidemic will have a significant impact on the health care system globally. Lifestyle interventions, such as restricting calorie consumption and increasing physical activity, remain a major component of weight-reduction programs. The development of pharmacotherapy for the management of obesity is still at the infancy stage. Side effects have been the key issue for anti-obesity drugs previously withdrawn from the market. The focus of this review, lorcaserin, is a selective serotonin receptor agonist that is currently undergoing Phase III evaluations. The efficacy of this drug in reducing body weight and improving metabolic parameters of obese patients has been demonstrated in two recent clinical trials. The available evidence indicates that this drug does not show unwanted effects on heart valves or pulmonary artery pressure, and the treatment improves the risk factors for type 2 diabetes and cardiovascular diseases. Despite these promising results, additional experimental and clinical studies are critical for the approval of lorcaserin as a new anti-obesity monodrug therapy by the US Food and Drug Administration.

Topics: Animals; Anti-Obesity Agents; Benzazepines; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Humans; Obesity; Risk Factors; Serotonin Receptor Agonists; Weight Loss

Lorcaserin, a selective serotonin 2C receptor agonist, is an effective pharmacologic weight-loss therapy that improves several cardiovascular risk factors. The long-term clinical cardiovascular and metabolic safety and efficacy in patients with elevated cardiovascular risk are unknown.. CAMELLIA-TIMI 61 (NCT02019264) is a randomized, double-blind, placebo-controlled, multinational clinical trial designed to evaluate the safety and efficacy of lorcaserin with regard to major adverse cardiovascular events and progression to diabetes in overweight or obese patients at high cardiovascular risk. Overweight or obese patients either with established cardiovascular disease or with diabetes and at least 1 other cardiovascular risk factor were randomized in a 1:1 ratio to lorcaserin 10 mg twice daily or matching placebo. The primary safety objective is to assess for noninferiority of lorcaserin for the composite end point of cardiovascular death, myocardial infarction, or stroke (major adverse cardiovascular event [MACE]) (with noninferiority defined as the upper bound of a 1-sided 97.5% CI excluding a hazard ratio of 1.4) compared with placebo assessed at an interim analysis with 460 adjudicated events. The efficacy objectives, assessed at study completion, will evaluate the superiority of lorcaserin for the primary composite end point of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, heart failure, or any coronary revascularization (MACE+) and the key secondary end point of conversion to diabetes. Recruitment began in January 2014 and was completed in November 2015 resulting in a total population of 12,000 patients. The trial is planned to continue until at least 1,401 adjudicated MACE+ events are accrued and the median treatment duration exceeds 2.5 years.. CAMELLIA-TIMI 61 is investigating the safety and efficacy of lorcaserin for MACEs and conversion to diabetes in overweight or obese patients with established cardiovascular disease or multiple cardiovascular risk factors.

Topics: Aged; Anti-Obesity Agents; Benzazepines; Biomarkers; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Disease Progression; Double-Blind Method; Echocardiography; Humans; Middle Aged; Obesity; Overweight; Research Design; Risk Factors; Serotonin 5-HT2 Receptor Agonists; Weight Loss

This study aimed to evaluate the effects of lorcaserin on body weight, cardiovascular risk factors, and safety in obese patients in Taiwan.. In this double-blind, randomised controlled trial, 171 obese adults were assigned to receive lorcaserin at a dose of 10mg, or placebo, twice a day for 24weeks. Diet and exercise counselling were given to all patients through the treatment period. Primary outcomes were proportion of patients achieving at least 5% and 10% reduction in body weight and mean change in body weight. Safety and tolerability endpoints such as Beck Depression Inventory-II, blood biochemistry, vital signs, and electrocardiogram were monitored.. More patients receiving lorcaserin lost at least 5% body weight than receiving placebo (52.4% and 28.1%, P=0.001) with an average weight reduction of 5.8kg (95% CI: -6.91, -4.70) in lorcaserin group and those of 3.6kg (95% CI: -4.95, -2.33) in placebo group (P<0.05). The most common adverse effect with greater incidence in the lorcaserin group was self-limited dizziness. Serious adverse effect were rare and was reported by slightly more patients taking placebo than lorcaserin.. In this multicentre, double-blinded placebo-controlled trial, lorcaserin was effective and well-tolerable in Asia group.

Topics: Adult; Anti-Obesity Agents; Asian People; Benzazepines; Body Mass Index; Cardiovascular Diseases; Double-Blind Method; Female; Heart Rate; Humans; Male; Middle Aged; Obesity; Treatment Outcome; Weight Loss; Young Adult

Lorcaserin, 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.. We 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.. At 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).. In 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 .).

Topics: Aged; Anti-Obesity Agents; Aortic Valve Insufficiency; Benzazepines; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Follow-Up Studies; Humans; Hypertension, Pulmonary; Hypoglycemia; Male; Middle Aged; Obesity; Overweight; Risk Factors; Weight Loss

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.

Topics: Absorptiometry, Photon; Adolescent; Adult; Aged; Anti-Obesity Agents; Benzazepines; Body Mass Index; Cardiovascular Diseases; Double-Blind Method; Echocardiography; Female; Humans; Lipids; Male; Middle Aged; Obesity; Overweight; Receptor, Serotonin, 5-HT2C; Risk Factors; Sample Size; Serotonin 5-HT2 Receptor Agonists; Weight Loss; Young Adult

Lorcaserin is a selective serotonin 2C receptor agonist that could be useful in reducing body weight.. In this double-blind clinical trial, we randomly assigned 3182 obese or overweight adults (mean body-mass index [the weight in kilograms divided by the square of the height in meters] of 36.2) to receive lorcaserin at a dose of 10 mg, or placebo, twice daily for 52 weeks. All patients also underwent diet and exercise counseling. At week 52, patients in the placebo group continued to receive placebo but patients in the lorcaserin group were randomly reassigned to receive either placebo or lorcaserin. Primary outcomes were weight loss at 1 year and maintenance of weight loss at 2 years. Serial echocardiography was used to identify patients in whom valvulopathy (as defined by the Food and Drug Administration) developed.. At 1 year, 55.4% of patients (883 of 1595) receiving lorcaserin and 45.1% of patients (716 of 1587) receiving placebo remained in the trial; 1553 patients continued into year 2. At 1 year, 47.5% of patients in the lorcaserin group and 20.3% in the placebo group had lost 5% or more of their body weight (P<0.001), corresponding to an average loss of 5.8+/-0.2 kg with lorcaserin and 2.2+/-0.1 kg with placebo during year 1 (P<0.001). Among the patients who received lorcaserin during year 1 and who had lost 5% or more of their baseline weight at 1 year, the loss was maintained in more patients who continued to receive lorcaserin during year 2 (67.9%) than in patients who received placebo during year 2 (50.3%, P<0.001). Among 2472 patients evaluated at 1 year and 1127 evaluated at 2 years, the rate of cardiac valvulopathy was not increased with the use of lorcaserin. Among the most frequent adverse events reported with lorcaserin were headache, dizziness, and nausea. The rates of serious adverse events in the two groups were similar.. In conjunction with behavioral modification, lorcaserin was associated with significant weight loss and improved maintenance of weight loss, as compared with placebo. (Funded by Arena Pharmaceuticals; ClinicalTrials.gov number, NCT00395135.)

Topics: Adult; Anti-Obesity Agents; Behavior Therapy; Benzazepines; Blood Pressure; Cardiovascular Diseases; Combined Modality Therapy; Double-Blind Method; Female; Heart Valve Diseases; Humans; Insulin; Intention to Treat Analysis; Male; Middle Aged; Obesity; Overweight; Risk Factors; Serotonin 5-HT2 Receptor Agonists; Serotonin Receptor Agonists; Waist Circumference; Weight Loss

Over the past several decades, many antiobesity drugs have been withdrawn from the market due to unanticipated adverse events, often involving cardiotoxicity. This study aimed to evaluate the presence of cardiovascular safety signals with currently marketed antiobesity drugs.. We used the US Food and Drug Administration Adverse Event Reporting System (FAERS) database and retrieved data from January 2013 through December 2018. We performed disproportionality analyses to detect cardiovascular safety signals with three antiobesity drugs recently approved for marketing: lorcaserin, naltrexone-bupropion, phentermine, and phentermine-topiramate. Three main cardiovascular outcomes were evaluated: valvular disorders, and pulmonary hypertension (PH) and other cardiovascular events (myocardial infarction, stroke, cardiovascular death, cardiac failure, and arrhythmia).. During the evaluated period, a total of 6,787,840 adverse event reports were submitted to FAERS. Of these, 2687 involved lorcaserin, 3960 involved phentermine/phentermine-topiramate, and 2873 involved naltrexone-bupropion. Lorcaserin was associated with a significantly greater proportion of reports of valvular disorders (ROR = 4.39; 95% CI 2.72-5.07). None of the antiobesity drugs were associated with a safety signal for valvulopathy, PH, or other cardiovascular events.. Our analyses revealed a signal for valvular disorders with lorcaserin and did not detect a safety signal for other cardiovascular events with recently approved antiobesity drugs. Further research is needed to explore and validate this signal.

Topics: Adult; Adverse Drug Reaction Reporting Systems; Aged; Anti-Obesity Agents; Benzazepines; Cardiovascular Diseases; Databases, Factual; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Male; Middle Aged; Naltrexone; Obesity; Phentermine; United States; United States Food and Drug Administration