lorcaserin and Weight-Loss

As a chronic and relapsing disease, obesity impairs metabolism and causes cardiovascular diseases. Although behavioral modification is important for the treatment of obesity, it is difficult to achieve an ideal weight or sustain the process of long-term weight loss. Therefore, the obesity control guidelines strongly recommend lifestyle interventions along with medical treatment for patients who are overweight. There is sufficient evidence supporting that pharmacotherapy in combination with behavior-based interventions can result in significant weight loss and improved cardiometabolism.. Recent meta-analyses of new anti-obesity drugs and their weight-loss efficacy have shown that the overall placebo-subtracted weight reduction (%) for at least 12 months ranged from 2.9 to 6.8% for the following drugs: phentermine/topiramate (6.8%), liraglutide (5.4%), naltrexone/bupropion (4.0%), orlistat (2.9%), and lorcaserin (3.1%). However, very recently, on February 13, 2020, the US Food and Drug Administration (FDA) ordered the withdrawal of lorcaserin from markets, as a clinical trial to assess drug safety showed an increased risk of cancer. Currently, the anti-obesity medications that have been approved by the FDA for chronic weight management are orlistat, phentermine/topiramate, naltrexone/bupropion, and liraglutide. However, they are costly and may have adverse effects in some individuals. Therefore, drug therapy should be initiated in obese individuals after weighing its benefits and risks. One of the strategies for long-term obesity control is that anti-obesity medications should be tailored for specific patients depending on their chronic conditions, comorbidities, and preferences.

Topics: Animals; Anti-Obesity Agents; Benzazepines; Bupropion; Humans; Liraglutide; Naltrexone; Obesity; Orlistat; Overweight; Phentermine; Topiramate; United States; United States Food and Drug Administration; Weight Loss

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

Topics: Anti-Obesity Agents; Benzazepines; Body Weight; Humans; Obesity; Randomized Controlled Trials as Topic; Serotonin 5-HT2 Receptor Agonists; Weight Loss

Four new medicines-liraglutide, lorcaserin, bupropion/naltrexone, and phentermine/topiramate-have been recently added to the pharmacological arsenal for obesity treatment and could represent important tools to manage this epidemic disease. To achieve satisfactory anti-obesity goals, the use of these new medicines should be optimized and tailored to specific patient subpopulations also by applying dose adjustments if needed. In the present review, we posit that gender could be among the factors influencing the activity of the new obesity drugs both because of pharmacokinetic and pharmacodynamic factors. Although evidence from premarketing clinical studies suggested that no dose adjustment by gender is necessary for any of these new medicines, these studies were not specifically designed to identify gender-related differences. This observation, together with the strong theoretical background supporting the hypothesis of a gender-dimorphic response, strongly call upon an urgent need of new real-life data on gender-related difference in the pharmacology of these new obesity drugs.

Topics: Anti-Obesity Agents; Benzazepines; Bupropion; Dose-Response Relationship, Drug; Drug Combinations; Female; Humans; Liraglutide; Male; Naltrexone; Obesity; Patient Selection; Sex Factors; Topiramate; Treatment Outcome; 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

Type 2 diabetes (T2DM) is associated with significant morbidity and mortality. Obesity is one of the main risk factors for T2DM and its management requires a multidisciplinary approach, which may include pharmacotherapy.. In this paper, data on efficacy, tolerability and safety of FDA-approved pharmacotherapies for obesity (orlistat, phentermine/topiramate extended-release, lorcaserin, bupropion sustained release/naltrexone sustained release and liraglutide) are reviewed, focusing on individuals with type 2 diabetes.. Obesity is the major pathophysiologic driver of T2DM; conversely 5-10% weight loss leads to significant improvement in glycemic control, lipids and blood pressure. Weight loss maintenance is difficult with lifestyle interventions alone and may require adjunctive therapies. There is good evidence for the efficacy and tolerability of approved anti-obesity pharmacotherapies in individuals with T2DM, with current cardiovascular safety data being most favorable for liraglutide, orlistat and lorcaserin. Given the link between obesity and T2DM, a weight-centric therapeutic approach including use of weight reducing anti-diabetic therapies, and anti-obesity pharmacotherapies is both intuitive and rational to improve glycemic and other metabolic outcomes in patients with T2DM.

Topics: Anti-Obesity Agents; Benzazepines; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Drug Compounding; Humans; Lactones; Liraglutide; Obesity; Orlistat; Phentermine; Weight Loss

The treatment of childhood obesity represents a greater challenge for pediatricians. To date, it is multidisciplinary, including behavioral, dietary, pharmacological, and surgical options. Given the limited efficacy of available treatments, scientific research on finding new solutions is very active. Several drugs comprising Metformin, Glucagon-like peptide- 1 receptor agonists, Naltrexone-bupropion, Phentermine-Topiramate, and Lorcaserin have been studied as pediatric antiobesity agents. Findings from clinical trials showed a modest but significant effect of these drugs on weight loss, but long-term studies are needed to better define their exact role. Bariatric surgery is also promising for extremely obese adolescents. Moreover, a novel approach to treat obesity might be represented by compounds inducing browning of white adipose tissue, a complex process involved in body energy homeostasis, but at present evidence in humans is lacking. We aimed to review the current knowledge regarding the available new options for pediatric obesity treatment.

Topics: Adolescent; Anti-Obesity Agents; Bariatric Surgery; Benzazepines; Child; Diet; Humans; Naltrexone; Pediatric Obesity; Weight Loss

This review provides an overview of the current state of drug therapy for obesity, with a focus on four new drug therapies-lorcaserin, phentermine/topiramate, naltrexone/bupropion, and liraglutide 3.0 mg-which have been approved by the US Food and Drug Administration (FDA) for long-term management of obesity since 2012. Topics discussed in this paper include rationale for pharmacotherapy, history of antiobesity drugs, and efficacy and safety data from randomized controlled trials with implications for clinical practice.. Weight loss achieved by currently approved drugs ranges from approximately 3 to 9%, above and beyond weight loss with lifestyle counseling alone, after a year. Response and attrition rates in clinical trials indicate that the benefits of pharmacotherapy range from substantial for some patients, modest for others, and no benefits for others still. Decisions regarding selection of a suitable drug from the available pharmacotherapy options and duration of treatment should be based on the expected and observed benefit-to-risk balance and tailored to the needs of each individual patient using the principles of shared decision-making.

Topics: Anti-Obesity Agents; Benzazepines; Clinical Trials as Topic; Fructose; Humans; Life Style; Liraglutide; Obesity; Phentermine; Topiramate; Weight Loss

Lorcaserin is a serotonin 2C receptor antagonist that was FDA approved in 2012. Lorcaserin is recently available as an extended-release (ER) formulation for the treatment of obesity as an adjunct to lifestyle modification. Areas covered: The pharmacokinetics, pharmacodynamics, efficacy, and safety of lorcaserin ER will be reviewed. Expert opinion: Lorcaserin ER 20mg daily provides drug exposure bioequivalent to lorcaserin immediate release (IR) 10mg twice daily. Lorcaserin IR is associated with 3.3 and 3.0% placebo-subtracted weight loss in patients without and with diabetes, respectively. A1C was reduced by 0.9% in patients with diabetes. Common side effects include headache, dry mouth, constipation, dizziness, fatigue, and nausea. Lorcaserin provides potential advantages over other antiobesity medications in regards to tolerability and simplicity of medication initiation, but may not be as effective as other options. Lorcaserin ER offers improved ease of administration and anticipated adherence compared to the IR formulation. The place in therapy for lorcaserin ER and other antiobesity medications will be further clarified by results of pending clinical trials addressing cardiovascular outcomes as well as the role pharmacogenomics and comorbid disease states may play in choosing patient-specific therapy.

Topics: Anti-Obesity Agents; Benzazepines; Delayed-Action Preparations; Humans; Medication Adherence; Obesity; Receptor, Serotonin, 5-HT2C; Serotonin 5-HT2 Receptor Antagonists; Weight Loss

To review and compare the phase 3 clinical trial evidence on the 4 new pharmacological agents approved for the management of overweight and obesity.. Searches were performed (from 1966 through January 2016) in PubMed/MEDLINE, Scientific Citation Index, and product package inserts to identify key phase 3 clinical trials that were used in the approval of each agent.. Phase 3 clinical trials that listed end points of ≥5% and ≥10% weight loss benchmarks from baseline as well as total percentage of weight loss by participants were selected for the review.. No head-to-head trials have been identified between these agents at this point, which limits comparisons across agents. Phentermine/topiramate ER appeared to have the best overall average weight loss from baseline as well as highest percentages of patients achieving both ≥5% and ≥10% weight loss benchmarks, followed second by naltrexone/bupropion, and then liraglutide, with lorcaserin showing the lowest rates. Phentermine/topiramate ER completion rates were highest for both treatment and placebo groups, followed by liraglutide, with lorcaserin and naltrexone/bupropion showing similar completion rates, below that of the other 2 agents. Common side effects reported differed between agents, although the most common adverse events reported were gastrointestinal in nature, with liraglutide demonstrating the highest reported rates and lorcaserin demonstrating the lowest.. These 4 new pharmacological agents represent new options for the clinician to utilize when trying to manage the problem of obesity. No clear first-line agent has emerged, so treatment decisions should be based on patient-specific factors.

Topics: Anti-Obesity Agents; Benzazepines; Bupropion; Clinical Trials, Phase III as Topic; Drug Combinations; Fructose; Humans; Liraglutide; Naltrexone; Obesity; Phentermine; Topiramate; Weight Loss

Five medications have been approved for the management of obesity, but data on comparative effectiveness are limited.. To compare weight loss and adverse events among drug treatments for obesity using a systematic review and network meta-analysis.. MEDLINE, EMBASE, Web of Science, Scopus, and Cochrane Central from inception to March 23, 2016; clinical trial registries.. Randomized clinical trials conducted among overweight and obese adults treated with US Food and Drug Administration-approved long-term weight loss agents (orlistat, lorcaserin, naltrexone-bupropion, phentermine-topiramate, or liraglutide) for at least 1 year compared with another active agent or placebo.. Two investigators identified studies and independently abstracted data using a predefined protocol. A Bayesian network meta-analysis was performed and relative ranking of agents was assessed using surface under the cumulative ranking (SUCRA) probabilities. Quality of evidence was assessed using GRADE criteria.. Proportions of patients with at least 5% weight loss and at least 10% weight loss, magnitude of decrease in weight, and discontinuation of therapy because of adverse events at 1 year.. Twenty-eight randomized clinical trials with 29 018 patients (median age, 46 years; 74% women; median baseline body weight, 100.5 kg; median baseline body mass index, 36.1) were included. A median 23% of placebo participants had at least 5% weight loss vs 75% of participants taking phentermine-topiramate (odds ratio [OR], 9.22; 95% credible interval [CrI], 6.63-12.85; SUCRA, 0.95), 63% of participants taking liraglutide (OR, 5.54; 95% CrI, 4.16-7.78; SUCRA, 0.83), 55% taking naltrexone-bupropion (OR, 3.96; 95% CrI, 3.03-5.11; SUCRA, 0.60), 49% taking lorcaserin (OR, 3.10; 95% CrI, 2.38-4.05; SUCRA, 0.39), and 44% taking orlistat (OR, 2.70; 95% CrI, 2.34-3.09; SUCRA, 0.22). All active agents were associated with significant excess weight loss compared with placebo at 1 year-phentermine-topiramate, 8.8 kg (95% CrI, -10.20 to -7.42 kg); liraglutide, 5.3 kg (95% CrI, -6.06 to -4.52 kg); naltrexone-bupropion, 5.0 kg (95% CrI, -5.94 to -3.96 kg); lorcaserin, 3.2 kg (95% CrI, -3.97 to -2.46 kg); and orlistat, 2.6 kg (95% CrI, -3.04 to -2.16 kg). Compared with placebo, liraglutide (OR, 2.95; 95% CrI, 2.11-4.23) and naltrexone-bupropion (OR, 2.64; 95% CrI, 2.10-3.35) were associated with the highest odds of adverse event-related treatment discontinuation. High attrition rates (30%-45% in all trials) were associated with lower confidence in estimates.. Among overweight or obese adults, orlistat, lorcaserin, naltrexone-bupropion, phentermine-topiramate, and liraglutide, compared with placebo, were each associated with achieving at least 5% weight loss at 52 weeks. Phentermine-topiramate and liraglutide were associated with the highest odds of achieving at least 5% weight loss.

Topics: Anti-Obesity Agents; Bayes Theorem; Benzazepines; Drug Combinations; Female; Fructose; Humans; Lactones; Liraglutide; Male; Middle Aged; Naltrexone; Obesity; Orlistat; Phentermine; Randomized Controlled Trials as Topic; Topiramate; Weight Loss

For the first time, patients who are obese are able to benefit from 5 different FDA approved pharmacologic agents for chronic weight management. Although weight loss from all of these medications was limited to 5% to 10% of total body weight loss in the Phase III clinical trials, patients are capable of losing more weight when a cumulative approach of diet, exercise, and multiple medications are used. A pilot study of adding phentermine to lorcaserin yielded double the weight loss than lorcaserin alone. A higher percentage of total body weight is lost with use of combination phentermine/topiramate compared to orlistat, lorcaserin, and bupropion/naltrexone but there are more contraindications to its use and potential cardiovascular adverse effects due to adrenergic agonism. Lorcaserin and bupropion/naltrexone yielded similar weight loss but carry different adverse effect profiles and interactions with other psychiatric medications may preclude use of one over the other. When choosing a medication for obesity, several factors need to be considered, such as comorbidities, medication interactions, and risk of potential adverse effects.

Topics: Adult; Anti-Obesity Agents; Appetite Depressants; Benzazepines; Body Weight; Clinical Trials as Topic; Clinical Trials, Phase III as Topic; Female; Fructose; Humans; Obesity; Phentermine; Pilot Projects; Topiramate; Weight Loss

In 2014 we have 4 new weight loss medications and one older medication with very different mechanisms of action – all approved for chronic weight management. Each medication has its own unique risk profile that makes patient selection important. Knowledge of the contraindications and safety issues can guide physicians to the most appropriate choice for a particular patient. Obesity medicine is entering a new era where our available options for prescribing have been very well studied. There should be no surprises, because bupropion, naltrexone, phentermine, topiramate and liraglutide have been prescribed for many years in millions of patients and lorcaserin has high specificity for a single receptor subtype. The FDA demanded very detailed risk-oriented studies to have these medications approved. In addition, the FDA has established REMS programs or risk management strategies to help ensure that the patients do not receive inappropriate medications. These medications were approved by the US FDA after very thorough testing. The decision to approve these medications was based on the benefits out-weighing the risks. Thus, if following the appropriate guidelines according to package labels, the practitioner can feel safe in prescribing these medications.

Topics: Anti-Obesity Agents; Benzazepines; Bupropion; Delayed-Action Preparations; Drug-Related Side Effects and Adverse Reactions; Drugs, Investigational; Fructose; Glucagon-Like Peptide 1; Humans; Liraglutide; Naltrexone; Obesity; Phentermine; Topiramate; United States; United States Food and Drug Administration; Weight Loss

Obesity drugs have had a chequered history. In the recent past, only the low efficacy, pancreatic lipase inhibitor orlistat was available worldwide and it was little used. The 5HT2C agonist, lorcaserin, and two combinations of old drugs have been approved in the United States but not in Europe. The diabetes drug liraglutide has been approved in both the US and Europe and seems likely to be most widely accepted. In view of regulators' caution in approving obesity drugs, some (like beloranib) may initially be progressed for niche obesity markets. New drug targets have been identified in brown adipose tissue with the aim of not only activating thermogenesis but also increasing the capacity for thermogenesis in this tissue. Attempts are being made to match the efficacy of bariatric surgery by mimicking multiple gut hormones. Unapproved pharmacotherapies are tempting for some patients. Others remain optimistic about more conventional routes to pharmacotherapy.

Topics: Adipose Tissue, Brown; Anti-Obesity Agents; Appetite Depressants; Benzazepines; Cinnamates; Clinical Trials as Topic; Cyclohexanes; Drug Approval; Drug Combinations; Epoxy Compounds; Europe; Humans; Lactones; Liraglutide; Molecular Targeted Therapy; Obesity; Orlistat; Sesquiterpenes; Thermogenesis; United States; Weight Loss

To use meta-analytic techniques to quantitatively evaluate the efficacy of orlistat and lorcaserin in the treatment of people who are overweight and obese.. We identified publications from searches of electronic databases and extracted data from studies that compared orlistat or lorcaserin to lifestyle advice (standard care), placebo, sibutramine, rimonabant or metformin and collected information on waist circumference change or withdrawals due to adverse events (AEs). A mixed treatment comparison (MTC) meta-analysis was performed on the data extracted.. Orlistat was found to be significantly better than placebo and standard care in reducing waist circumference at 6 and 12 months; orlistat reduced waist circumference by -6.96 cm [95% credible interval (CrI): -8.93, -4.96 cm] compared to standard care at 6 months. The results suggested that lorcaserin reduced waist circumference by a greater amount than all other interventions at 12 months, for example, lorcaserin lead to a greater reduction of -2.45 cm (95% CrI: -4.99, 0.08 cm) in comparison to placebo, although these differences were not statistically significant. Although data were very limited, metformin reduced waist circumference by a greater amount (-2.11 cm, 95% CI: -1.00, -3.22 cm) than orlistat at 6 months. On average, 6.5% of patients on orlistat and 5.4% of those on lorcaserin discontinued their treatment due to AEs at 12 months.. Orlistat should be considered as an addition to lifestyle interventions in the treatment of obesity. Lorcaserin has recently been approved by the US Food and Drug Administration (FDA) and these results suggest that it is similar in both efficacy and safety compared to orlistat.

Topics: Anti-Obesity Agents; Benzazepines; Body Mass Index; Combined Modality Therapy; Drug Administration Schedule; Female; Humans; Lactones; Male; Metformin; Obesity; Orlistat; Risk Reduction Behavior; Treatment Outcome; Waist Circumference; Weight Loss

The number of bariatric surgical procedures performed has increased dramatically. This review discusses the clinical and physiological changes, and in particular, the mechanisms behind weight loss and glycaemic improvements, observed following the gastric bypass, sleeve gastrectomy and gastric banding bariatric procedures. The review then examines how close we are to mimicking the clinical or physiological effects of surgery through less invasive and safer modern interventions that are currently available for clinical use. These include dietary interventions, orlistat, lorcaserin, phentermine/topiramate, glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, pramlintide, dapagliflozin, the duodenal-jejunal bypass liner, gastric pacemakers and gastric balloons. We conclude that, based on the most recent trials, we cannot fully mimic the clinical or physiological effects of surgery; however, we are getting closer. A 'medical bypass' may not be as far in the future as we previously thought, as the physician's armamentarium against obesity and type 2 diabetes has recently got stronger through the use of specific dietary modifications, novel medical devices and pharmacotherapy. Novel therapeutic targets include not only appetite but also taste/food preferences, energy expenditure, gut microbiota, bile acid signalling, inflammation, preservation of β-cell function and hepatic glucose output, among others. Although there are no magic bullets, an integrated multimodal approach may yield success. Non-surgical interventions that mimic the metabolic benefits of bariatric surgery, with a reduced morbidity and mortality burden, remain tenable alternatives for patients and health-care professionals.

Topics: Anti-Obesity Agents; Bariatric Surgery; Benzazepines; Benzhydryl Compounds; Blood Glucose; Diabetes Mellitus, Type 2; Exercise; Feeding Behavior; Female; Fructose; Glucagon-Like Peptide-1 Receptor; Glucosides; Glycated Hemoglobin; Homeostasis; Humans; Islet Amyloid Polypeptide; Lactones; Male; Minimally Invasive Surgical Procedures; Obesity, Morbid; Orlistat; Phentermine; Receptors, Glucagon; Topiramate; Treatment Outcome; Weight Loss

A short overview of new drugs approved for the treatment of obesity (lorcaserin, phentermine/topiramate combination) as well as those with a perspective for approval as antiobesity drugs (cetilistat, naltrexone/bupropion combination, liraglutide) is presented. All these drugs produce significant weight loss accompanied by reductions in cardiometabolic health risks. Although the adverse events were rather rare and tended to decrease with the duration of treatment with most of these medications, the drug-specific safety concerns should be seriously considered. In order to ensure an appropriate, efficient and safe implementation of novel antiobesity drugs into the comprehensive treatment of obesity, it will be necessary to establish a network of physicians and other health-care providers well educated in obesity management.

Topics: Anti-Obesity Agents; Benzazepines; Benzoxazines; Bupropion; Drug Combinations; Fructose; Glucagon-Like Peptide 1; Humans; Liraglutide; Naltrexone; Obesity; Phentermine; Topiramate; Weight Loss

Medications for the treatment of obesity began to appear in the late 19th and early 20th century. Amphetamine-addiction led to the search for similar drugs without addictive properties. Four sympathomimetic drugs currently approved in the US arose from this search, but may not be approved elsewhere. When noradrenergic drugs were combined with serotonergic drugs, additional weight loss was induced. At present there are three drugs (orlistat, phentermine/topiramate and lorcaserin) approved for long-term use and four sympathomimetic drugs approved by the US FDA for short-term treatment of obesity. Leptin produced in fat cells and glucagon-like peptide-1, a gastrointestinal hormone, provide a new molecular basis for treatment of obesity. New classes of agents acting on the melanocortin system in the brain or mimicking GLP-1 have been tried with variable success. Combination therapy can substantially increase weight loss; a promising approach for the future.

Topics: Anti-Obesity Agents; Benzazepines; Drug Therapy, Combination; Fructose; Humans; Lactones; Obesity; Orlistat; Phentermine; Topiramate; Weight Loss

Oral lorcaserin (BELVIQ(®)), a selective serotonin 5-HT2C receptor agonist, is indicated in the US as an adjunct to diet and exercise in the chronic weight management of obese adults, or overweight adults with at least one weight-related comorbidity (e.g. dyslipidaemia, hypertension, type 2 diabetes). This article reviews the pharmacological properties, therapeutic efficacy and tolerability of oral lorcaserin in this patient population. In three large randomized, double-blind, multicentre studies, oral lorcaserin was more effective than placebo in the management of obese and overweight adults with or without type 2 diabetes mellitus. Following 12 months' therapy, significantly higher proportions of lorcaserin than placebo recipients achieved a ≥5 and ≥10 % reduction from baseline in their bodyweight and a significant between-group difference favouring lorcaserin over placebo was observed for the change from baseline in bodyweight. Moreover, among patients who had achieved a ≥5 % reduction in their bodyweight after 12 months' therapy with lorcaserin, a significantly higher proportion who received lorcaserin for a further 12 months than those who switched to placebo maintained ≥5 % weight loss at 24 months. In general, oral lorcaserin was well tolerated in clinical studies, with hypoglycaemia and headache the most frequently reported adverse events in those with or without type 2 diabetes, respectively. According to a pooled analysis, the risk of US-FDA-defined valvulopathy with lorcaserin is generally low and not statistically significantly different from placebo. From these and other data, the FDA has concluded that lorcaserin is unlikely to elevate the risk of valvulopathy.

Topics: Administration, Oral; Animals; Anti-Obesity Agents; Benzazepines; Chronic Disease; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Disease Management; Humans; Obesity; Overweight; Serotonin 5-HT2 Receptor Agonists; Weight Loss

Obesity has become an epidemic in the United States and its prevalence continues to increase. Adjunctive treatment with pharmacotherapy is often reserved for individuals who fail to achieve their intended weight goals with diet and exercise alone. Current approved therapies for weight loss include phentermine, diethylpropion, orlistat, and phentermine/topiramate. The objective of this paper was to review the place of lorcaserin, a novel serotonin 2C agonist, which was FDA approved in July 2012. Unlike contemporary lipase inhibitors and sympathomimetic amines, lorcaserin is purported to reduce food consumption and increase satiety.. A systematic review of the literature for all relevant articles was performed through January 2013 using MEDLINE, Web of Science, and International Pharmaceutical Abstracts using key words related to lorcaserin.. Three phase III clinical studies have been published evaluating the efficacy and safety of lorcaserin in various obese populations. A higher proportion of patients receiving lorcaserin (∼47%) lost more than 5% body weight from baseline in comparison with the placebo group (∼25%; p < 0.05 in all studies). Those receiving the recommended dose of lorcaserin 10 mg twice daily lost on average ∼6 kg of body weight from baseline versus ∼3 kg with placebo. Patients with diabetes mellitus also saw significant reductions in their HbA1c with lorcaserin (∼0.9%) versus placebo (∼0.4%; p < 0.001). Lorcaserin is generally well tolerated with the most commonly experienced adverse events being nausea, dizziness, headache, upper respiratory tract infections, and nasopharyngitis. Cardiovascular evaluations showed no appreciable increase in valvulopathy with lorcaserin use versus placebo.. For now, pharmacists should continue to recommend the use of lorcaserin as a complement to, not in lieu of, ongoing lifestyle and behavioral modification.

Topics: Anti-Obesity Agents; Benzazepines; Body Weight; Eating; Humans; Obesity; Receptor, Serotonin, 5-HT2C; Serotonin 5-HT2 Receptor Agonists; Weight Loss

Obesity is an epidemic associated with significant morbidity. Lorcaserin , a novel serotonin 2C receptor antagonist, was recently approved as an adjunct to lifestyle modification for long-term weight loss and maintenance. Clinical studies in patients without diabetes demonstrated 5.8% mean weight loss from baseline with lorcaserin compared to 2.5% with placebo and over twice as many patients achieved ≥ 5% weight loss. Patients with diabetes achieved mean weight loss of 4.5% with lorcaserin compared to 1.5% with placebo as well as modest improvements in glycemic outcomes.. The authors review the pharmacology and clinical efficacy as well as the safety and tolerability of lorcaserin. This was achieved through a PubMed search (1960 - present) on lorcaserin to generate the key literature in the area. The lorcaserin package insert and Food and Drug Administration briefing documents were also used to identify relevant information. To assess long-term clinical efficacy and safety, the authors used studies with a minimum duration of one year.. Lorcaserin induces moderate but significant weight loss compared to placebo as an adjunct to lifestyle modification. Although head-to-head comparison trials are not available, lorcaserin is likely less effective but better tolerated than its recently approved competitor, phentermine/topiramate. Cardiovascular outcome data will be invaluable in determining lorcaserin's eventual utilization and place in therapy.

Topics: Benzazepines; Clinical Trials, Phase III as Topic; Drug Interactions; Fructose; Humans; Obesity; Randomized Controlled Trials as Topic; Receptor, Serotonin, 5-HT2C; Topiramate; Weight Loss

Obesity may lead to the development of multiple chronic disease states, including hypertension, dyslipidemia, and type 2 diabetes mellitus. Over a half billion adults worldwide are affected by obesity, and more than two-thirds of adults are either obese or overweight in the United States. Diet and exercise have been the mainstays of treatment in this population; however, once failed, noninvasive, long-term effective treatment modality is lacking, and medications may potentially fill the void. Lorcaserin and phentermine/topiramate were approved by the FDA in June 2012 and July 2012, respectively, as adjuncts to diet and exercise for chronic weight management of obese (body mass index [BMI] ≥ 30 kg/m2) or overweight (BMI ≥ 27 kg/m2) individuals with comorbidities.. To review the phase 3 trials of lorcaserin and phentermine/topiramate and provide managed care considerations that may be taken into account as a result.. A MEDLINE review was performed for articles published and available through September 17, 2012, using keywords "lorcaserin" or "phentermine/topiramate" with an emphasis on phase 3 trials. The literature search was limited to randomized controlled trials in humans published in the English language. Additional information on lorcaserin from its FDA review was obtained from the FDA website.. 5 pivotal phase 3 trials were identified: 3 for lorcaserin and 2 for phentermine/topiramate. Both agents demonstrated a statistically significant higher proportion of individuals who lost ≥ 5% of body weight, as well as higher mean weight loss when compared with placebo. Safety concerns for lorcaserin include cardiac valvulopathy and increased risk of psychiatric, cognitive, and serotonergic adverse effects. Teratogenicity and increased heart rate are major safety concerns regarding phentermine/topiramate.. Health care decision makers have many factors to consider when developing strategies to fight obesity. Despite a great need for new therapies to treat obesity, medications used for weight loss have significant side-effect profiles and contraindications that may limit therapy. An appropriate utilization management strategy is needed.

Topics: Adult; Anti-Obesity Agents; Appetite Depressants; Benzazepines; Body Weight; Clinical Trials, Phase III as Topic; Female; Fructose; Humans; Male; Obesity; Phentermine; Randomized Controlled Trials as Topic; Topiramate; Weight Loss

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/m 2 or in adult patients with an initial body mass index ≥ 27 kg/m 2 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.

Topics: Anti-Obesity Agents; Benzazepines; Body Composition; Body Weight; Clinical Trials, Phase III as Topic; Humans; Obesity; Receptor, Serotonin, 5-HT2C; Serotonin 5-HT2 Receptor Agonists; Weight Loss

Lorcaserin is a new anti-obesity drug recently approved by US Food and Drug Administration. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the association of lorcaserin therapy with weight loss and adverse events in obese adults (18-65 years old). Weight loss of 3.23 kg (95% confidence interval [CI]: 2.70, 3.75) and body mass index reduction of 1.16 kg m⁻² (95% CI: 0.98, 1.34) was observed compared with placebo in RCTs of 1 year duration. The use of lorcaserin for 8 and 12 weeks reduced weight of 1.60 kg (95% CI: 0.34, 2.86) and 2.9 kg (95% CI: 2.2, 3.5), respectively. In comparison to placebo, lorcaserin decreased waist circumference, blood pressure, total cholesterol, low-density lipoprotein-cholesterol and triglycerides, however did not statistically affect heart rate or high-density lipoprotein-cholesterol. Headache, nausea and dizziness were found to be significantly higher in the patients receiving lorcaserin than patients receiving placebo, whereas diarrhoea is no more likely than in patients receiving placebo. In conclusion, lorcaserin achieves modest weight loss and appears to be well tolerated. Clinical and pharmacovigilance studies with longer study duration are needed to inform of the long-term efficacy and safety of lorcaserin.

Topics: Adolescent; Adult; Aged; Anti-Obesity Agents; Benzazepines; Female; Humans; Male; Middle Aged; Obesity; Randomized Controlled Trials as Topic; Treatment Outcome; Weight Loss; Young Adult

The prevalence of obesity is rising worldwide, with the U.K. having the highest prevalence in Europe. Obesity is associated with significant morbidity and has substantial healthcare implications, with current projections estimating that by 2030 obesity will cost the NHS approximately pounds 2 billion each year. Lifestyle modification remains the cornerstone of anti-obesity treatment, but drugs can be introduced as adjuncts to assist and maintain weight loss. Some 1.45 million obesity-related prescriptions were dispensed in 2009, highlighting the high demand for obesity pharmacotherapy. At present, the lipase inhibitor orlistat (Xenical) is the only UK-approved long-term medical therapy for obesity. Double-blind clinical trials have shown that orlistat significantly increases weight loss compared to placebo, but the array of adverse side effects associated with orlistat limits its tolerability. The need for more effective and better-tolerated anti-obesity medications is clear and six therapies have reached phase-III trials.

Topics: Anti-Obesity Agents; Benzazepines; Benzoxazines; Bupropion; Clinical Trials as Topic; Drug Combinations; Fructose; Glucagon-Like Peptide 1; Humans; Lactones; Life Style; Liraglutide; Naltrexone; Obesity; Orlistat; Phentermine; Topiramate; Weight Loss

Lorcaserin is a selective 5-hydroxytryptamine receptor 2c agonist developed as a weight-loss drug. Phase II and III clinical trials support lorcaserin as not only reducing adiposity (i.e., fat mass), but also as improving the metabolic diseases commonly associated with adiposopathy (i.e., fat dysfunction). At the time of this writing, regulatory processes continue towards evaluating lorcaserin as a potentially marketed weight-loss and weight-maintenance agent. Some of the challenges facing lorcaserin are similar to the difficulties encountered by all investigational weight-loss therapeutic agents, which include evolving paths towards approval. While important for clinicians to understand approval hurdles for all therapeutics, it is especially critical for researchers and developers to grasp the unique regulatory complexities of anti-obesity agents. This article profiles lorcaserin as an illustrative example of general drug development regulatory processes, and specifically details the unique challenge of weight-loss drug development.

Topics: Animals; Anti-Obesity Agents; Benzazepines; Drug Approval; Drug Design; Humans; Obesity; United States; United States Food and Drug Administration; Weight Loss

The pharmacology, pharmacokinetics, and adverse effects of the selective serotonin (5-HT) agonist lorcaserin are reviewed, with an emphasis on efficacy and safety data from Phase III clinical trials.. Lorcaserin is highly selective for a subtype of 5-HT receptors important in appetite regulation, with low affinity for other 5-HT-receptor subtypes whose activation is thought to underlie serious cardiovascular adverse effects; such effects have been seen with nonselective serotonergic agents for weight loss (e.g., fenfluramine). In two Phase III trials of lorcaserin, the cumulative proportion of patients who achieved weight loss of ≥5% over 12 months was about 47% with lorcaserin use versus 20-25% among placebo users (p < 0.0001 for both trials). Lorcaserin was generally well tolerated in the clinical trials to date; nausea and vomiting, headache, and dizziness were the most commonly reported adverse effects. In two of the three Phase III trials to date, lorcaserin use was not found to increase the risk of cardiac valvulopathy; however, in the other Phase III trial, which focused on patients with diabetes, lorcaserin use was associated with an increased rate of new valvulopathy. In a carcinogenicity evaluation involving laboratory rats, lorcaserin was linked to the development of various malignancies, a finding with uncertain implications for its potential future use in humans.. Lorcaserin, a 5-HT(2C) agonist, has demonstrated efficacy in patients who are obese or are overweight with associated comorbidities. Phase III trials have found that more than 35% of patients lost greater than 5% of their baseline weight. The maker of lorcaserin has indicated it will continue to seek U.S. marketing approval of the drug for the indications of long-term weight loss and weight-loss maintenance in specific patient populations.

Topics: Animals; Anti-Obesity Agents; Benzazepines; Clinical Trials, Phase III as Topic; Humans; Obesity; Overweight; Rats; Receptor, Serotonin, 5-HT2C; Serotonin 5-HT2 Receptor Agonists; Weight Loss

This article examines the transitions in pharmacological therapy for obesity. It reviews the current options approved by the Food and Drug Administration and several drugs approved for other indications that can be used to treat obesity as well. Because weight regulation is complex and redundant systems protect against perceived starvation, optimal treatment of obesity in individual patients will likely require different combinations of behavioral, nutritional, pharmacologic, endoscopic, and surgical therapies.

Topics: Anti-Obesity Agents; Appetite Depressants; Bariatric Surgery; Benzazepines; Bupropion; Cyclobutanes; Ephedrine; Fenfluramine; Humans; Lactones; Naltrexone; Obesity; Orlistat; Phentermine; Weight Gain; Weight Loss

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

Individual responses to weight loss (WL) medications vary widely and prediction of response remains elusive.. We investigated biomarkers associated with use of lorcaserin (LOR), a 5HT2cR agonist that targets proopiomelanocortin (POMC) neurons that regulate energy and glucose homeostasis, to identify predictors of clinical efficacy.. Thirty individuals with obesity were treated with 7 days of placebo and LOR in a randomized crossover study. Nineteen participants continued on LOR for 6 months. Cerebrospinal fluid (CSF) POMC peptide measurements were used to identify potential biomarkers that predict WL. Insulin, leptin, and food intake during a meal were also studied.. LOR induced a significant decrease in CSF levels of the POMC prohormone and an increase in its processed peptide β-endorphin after 7 days; β-endorphin/POMC increased by 30% (P < .001). This was accompanied by a substantial decrease in insulin, glucose, and homeostasis model assessment of insulin resistance before WL. Changes in CSF POMC peptides persisted after WL (6.9%) at 6 months that were distinct from prior reports after diet alone. Changes in POMC, food intake, or other hormones did not predict WL. However, baseline CSF POMC correlated negatively with WL (P = .07) and a cutoff level of CSF POMC was identified that predicted more than 10% WL.. Our results provide evidence that LOR affects the brain melanocortin system in humans and that effectiveness is increased in individuals with lower melanocortin activity. Furthermore, early changes in CSF POMC parallel WL-independent improvements in glycemic indexes. Thus, assessment of melanocortin activity could provide a way to personalize pharmacotherapy of obesity with 5HT2cR agonists.

Topics: beta-Endorphin; Cross-Over Studies; Glucose; Humans; Insulin; Melanocortins; Obesity; Pro-Opiomelanocortin; Weight Loss

Growth differentiation factor 15 (GDF-15) is a stress-response cytokine proposed to be associated with body weight regulation.. The primary aim was to investigate changes of circulating intact GDF-15 (wildtype, non-carrier of the rs1058587 polymorphism coding for the H2O2D mutation) and total GDF-15 (measured irrespective of the mutation) in response to liraglutide (GLP-1 receptor agonist) and lorcaserin (5-HT2C receptor agonist), two pharmacologic agents that induce food intake and weight reduction. In addition, we perform exploratory correlations of total and intact GDF-15 with clinical, hormonal and metabolo-lipidomic parameters in humans with obesity.. We utilized two studies: 1) Study 1, a randomized, double-blinded, cross-over trial of liraglutide and placebo administration for 5 weeks in subjects with obesity (n = 20; BMI = 35.6 ± 5.9 kg/m2), in escalating doses starting at 0.6 mg/day on week 1 and increased every week, up to the highest dose of 3.0 mg/day during week 5. b) Study 2, a randomized, double-blinded trial of lorcaserin 10 mg twice daily, or placebo for 12-weeks in humans with obesity (n = 34 BMI = 37.4 ± 6.1 kg/m2). Total and intact GDF-15 levels were measured with novel enzyme-linked immunosorbent assays and the metabolomics and lipidomics analysis was performed with nuclear magnetic resonance spectroscopy.. Total and intact GDF-15 were positively correlated with diabetes risk index and trimethylamine N-oxide and negatively with eGFR. Despite significant changes in body weight, total and intact GDF-15 were not altered in response to liraglutide or lorcaserin treatment in subjects with obesity.. Total and intact GDF-15 levels are not altered in response to liraglutide or lorcaserin therapy and are thus not directly involved in the metabolic feedback loop pathways downstream of GLP1 or 5-HT2C receptor agonists. Since neither total nor intact GDF-15 levels were altered in response to weight loss, future studies are needed to elucidate the pathways activated by GDF-15 in humans and its role, if any, in body weight regulation and energy homeostasis.

Topics: Benzazepines; Body Weight; Double-Blind Method; Growth Differentiation Factor 15; Humans; Liraglutide; Obesity; Receptor, Serotonin, 5-HT2C; Serotonin 5-HT2 Receptor Agonists; Weight Loss

Early weight loss (EWL) in the first 1-2 months of behavioral treatment is a strong predictor of later total weight loss. It is not clear whether participants with lower early losses lose less in ongoing treatment or simply fail to overcome the smaller initial loss. Furthermore, no study has tested whether EWL in behavioral treatment predicts response to a different treatment modality, such as pharmacotherapy.. Data were from 170 participants with obesity (baseline BMI = 40.8 ± 5.8 kg/m2, 87.6% female; 71.3% Black) enrolled in a two-phase trial. Data from the weight loss phase, which provided weekly lifestyle counseling and a meal replacement diet, were used to examine the relationship between 4-week EWL and subsequent rate of weight loss in behavioral treatment. Data from the maintenance phase, in which 137 participants who had lost ≥5% of initial weight were randomized to 52 weeks of maintenance counseling with lorcaserin or placebo, were used to determine whether EWL with behavioral treatment affects the benefit of pharmacotherapy.. EWL in the first 4 weeks of behavioral treatment (3.6 ± 1.7%) predicted greater total losses at Week 14 (r2 = 0.61, p < .001) and a faster rate of weight loss in the subsequent 9 weeks of the program (p < .001). During the maintenance phase, lower EWL in behavioral treatment predicted a greater benefit of lorcaserin, in comparison with placebo, for the maintenance of a ≥5% loss at Weeks 24 and 52.. These findings support recommendations to modify treatment for individuals with low EWL.

Topics: Adult; Anti-Obesity Agents; Behavior Therapy; Benzazepines; Female; Humans; Life Style; Male; Middle Aged; Obesity; Prognosis; Treatment Outcome; Weight Loss

Improving the maintenance of lost weight remains a critical challenge, which can be addressed by long-term behavioral and/or pharmacological interventions.. This study investigated the efficacy of combined behavioral and pharmacological treatment in facilitating weight loss maintenance (WLM) in 137 adults (86.1% female; 68.6% black; BMI = 37.0 ± 5.6 kg/m. At 24 weeks post randomization, more lorcaserin-treated than placebo-treated participants maintained a ≥ 5% loss (73.9% vs. 57.4%; P = 0.033), and the lorcaserin-treated participants lost an additional 2.4 ± 0.8 kg versus a 0.6 ± 0.8 kg gain for placebo (P = 0.010). However, at week 52, groups did not differ on either co-primary outcome; 55.1% and 42.6%, respectively, maintained ≥ 5% loss (P = 0.110), with gains from randomization of 2.0 ± 0.8 kg and 2.5 ± 0.8 kg (P = 0.630), respectively. From the start of the LCD, groups maintained reductions of 7.8% and 6.6%, respectively (P = 0.318).. Combined behavioral and pharmacological treatment produced clinically meaningful long-term weight loss in this group of predominantly black participants. Lorcaserin initially improved upon weight loss achieved with WLM counseling, but this advantage was not maintained at 1 year.

Topics: Adult; Aged; Benzazepines; Caloric Restriction; Counseling; Female; Humans; Life Style; Male; Middle Aged; Obesity; Weight Loss; Young Adult

The objective of this study was to determine the effects of weight loss and weight loss maintenance (WLM) on weight-specific health-related quality of life in a 66-week trial.. Adults with obesity (N = 137, 86.1% female, 68.6% black, mean age = 46.1 years) who had lost ≥ 5% of initial weight in a 14-week intensive lifestyle intervention/low-calorie diet (LCD) program were randomly assigned to lorcaserin or placebo for an additional 52-week WLM program. The Impact of Weight on Quality of Life-Lite (IWQOL-Lite) scale (including five subscales), Patient Health Questionnaire-9 (depression), and Perceived Stress Scale were administered at the start of the 14-week LCD program, randomization, and week 52 of the randomized controlled trial (i.e., 66 weeks total).. Significant improvements in all outcomes, except weight-related public distress, were found following the 14-week LCD program (P values < 0.05). Improvements were largely maintained during the 52-week randomized controlled trial, despite weight regain of 2.0 to 2.5 kg across treatment groups. Participants who lost ≥ 10% of initial weight achieved greater improvements in physical function, self-esteem, sexual life, and the IWQOL-Lite total score than those who lost < 5% and did not differ from those who lost 5% to 9.9%.. Improvements in weight-specific health-related quality of life were achieved with moderate weight loss and were sustained during WLM.

Topics: Adult; Anti-Obesity Agents; Behavior Therapy; Benzazepines; Caloric Restriction; Counseling; Depression; Eating; Female; Humans; Life Style; Male; Mental Health; Middle Aged; Obesity; Quality of Life; Self Concept; Weight Loss; Weight Reduction Programs

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

Anti-obesity medication may help people maintain diet-induced reductions in appetite. The present exploratory analysis assessed the effects of lorcaserin on changes at 24 weeks post-randomization in emotion- and stress-related eating, food cravings and other measures of appetite (i.e. binge eating, cognitive restraint, disinhibition, hunger, preoccupation with eating and fullness). The parent study investigated the efficacy of combined lorcaserin and behavioural treatment in facilitating weight loss maintenance (WLM) in 137 adults (mean age = 46.1 years, 86.1% female, 68.6% black) who had lost ≥5% of initial weight during a 14-week, low-calorie diet (LCD) run-in. Participants were randomly assigned to lorcaserin or placebo and were provided with group WLM counselling sessions. Emotion- and stress-related eating, food cravings and appetite were measured at the start of the LCD (week -14), randomization (0) and week 24. From randomization, lorcaserin-treated participants had significantly greater improvements in emotion- and stress-related eating compared to placebo-treated participants (P = 0.04). However, groups did not differ significantly after randomization in changes in the frequency of food cravings, binge eating or other measures of appetite (Ps > 0.05). Compared to placebo, lorcaserin may improve emotion- and stress-related eating.

Topics: Adult; Appetite; Behavior Therapy; Benzazepines; Bulimia; Counseling; Craving; Eating; Emotions; Female; Humans; Life Style; Male; Middle Aged; Obesity; Placebos; Stress, Psychological; Treatment Outcome; Weight Loss

There is a direct relationship between bodyweight and risk of diabetes. Lorcaserin, a selective serotonin 2C receptor agonist that suppresses appetite, has been shown to facilitate sustained weight loss in obese or overweight patients. We aimed to evaluate the long-term effects of lorcaserin on diabetes prevention and remission.. In this randomised, double-blind, placebo-controlled trial done in eight countries, we recruited overweight or obese patients (body-mass index ≥27 kg/m. Lorcaserin decreases risk for incident diabetes, induces remission of hyperglycaemia, and reduces the risk of microvascular complications in obese and overweight patients, supporting the role of lorcaserin as an adjunct to lifestyle modification for chronic management of weight and metabolic health.. Eisai.

Topics: Aged; Appetite Depressants; Atherosclerosis; Benzazepines; Body Weight; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Male; Middle Aged; Obesity; Overweight; Prediabetic State; Remission Induction; Weight Loss

To assess the short-term tolerability of lorcaserin alone or with two dose regimens of phentermine.. This was a 12-week, randomized, double-blind, pilot safety study of N = 238 nondiabetic patients with obesity or overweight with ≥1 comorbidity randomized to lorcaserin 10 mg twice daily (BID; LOR BID) alone or with phentermine 15 mg once daily (QD; LOR BID+PHEN QD) or 15 mg twice daily (LOR BID+PHEN BID). Patients reporting ≥ 1 of 9 potentially serotonergic adverse events (AEs), mean weight loss (WL), and ≥5% WL are reported.. N = 238 were randomized, and N = 235 were treated. N = 94 reported potentially serotonergic AEs: 37.2% LOR BID, 42.3% LOR BID+PHEN QD, and 40.5% LOR BID+PHEN BID. AEs leading to discontinuation were reported approximately twice as often in the LOR BID+PHEN BID group versus the LOR BID group. Mean WL was 3.5 kg/3.3%, 7.0 kg/6.7%, and 7.6 kg/7.2% for LOR BID, LOR BID+PHEN QD, and LOR BID+PHEN BID, respectively. At least 5% WL was achieved by 28.2% LOR BID, 59.0% LOR BID+PHEN QD (P = 0.0002 vs. LOR BID), and 70.9% LOR BID+PHEN BID (P < 0.0001 vs. LOR BID) patients.. Phentermine added to lorcaserin enhanced short-term weight loss but did not increase incidence of potentially serotonergic AEs; however, phentermine twice daily increased discontinuation compared to both lorcaserin alone and lorcaserin plus phentermine once daily.

Topics: Adolescent; Adult; Anti-Obesity Agents; Benzazepines; Double-Blind Method; Female; Humans; Male; Middle Aged; Phentermine; Pilot Projects; Weight Loss; Young Adult

Few studies have examined the efficacy of recently approved medications for chronic weight management in facilitating the maintenance of lost weight. This paper provides an overview of the design and rationale for a trial investigating whether lorcaserin, when combined with behavioral weight loss maintenance sessions (WLM), will facilitate the maintenance of losses of ≥5% of initial weight.. In this two-phase trial, participants with obesity will enroll in a 14-week run-in diet program consisting of weekly group lifestyle modification sessions and a 1000-1200kcal/d meal replacement diet. Participants who complete this weight induction phase and lose at least 5% of initial weight will then be randomized to 52weeks of WLM plus lorcaserin or WLM plus placebo. We hypothesize that at 52weeks post randomization, participants assigned to WLM plus lorcaserin will achieve significantly better maintenance of the prior 5% weight loss.. We will recruit 182 adults with obesity to participate in the diet run-in, 136 of whom (75%) are expected to become eligible for the randomized controlled trial. Co-primary outcomes include the percentage of participants who maintain a loss of at least 5% of initial weight at week 52 and change in weight (kg) from randomization to week 52.. This two-phase design will allow us to determine the potential efficacy of chronic weight management using lorcaserin for maintaining initial losses of at least 5% body weight, induced by the use of a structured meal-replacement diet. This combined approach holds promise of achieving larger long-term weight losses.. NCT02388568 on ClinicalTrials.gov.

Topics: Adult; Benzazepines; Body Mass Index; Caloric Restriction; Combined Modality Therapy; Diet Therapy; Female; Healthy Lifestyle; Humans; Male; Middle Aged; Obesity; Outcome Assessment, Health Care; Research Design; Weight Loss

Lorcaserin, plus diet and exercise, has demonstrated significant weight loss and improved cardiometabolic parameters vs. placebo in patients with overweight/obesity in three randomized, placebo-controlled trials. We examined whether lorcaserin is also associated with greater improvements in health-related quality of life (HRQOL) and whether these improvements are wholly attributable to weight loss. Pooled data from Behavioral Modification and Lorcaserin for Overweight and Obesity Management (BLOOM), Behavioral Modification and Lorcaserin Second Study for Obesity Management (BLOSSOM) and BLOOM-Diabetes Mellitus (BLOOM-DM) trials were analysed (n = 5624). HRQOL was assessed at baseline and 52 weeks using the Impact of Weight on Quality of Life-Lite (IWQOL-Lite) questionnaire. Multiple mediation analyses were conducted to evaluate the mechanisms underlying improved HRQOL. Greater HRQOL improvements were observed at 52 weeks in lorcaserin vs. placebo (P < 0.0001). A greater percentage of lorcaserin patients (54.1%) experienced meaningful improvements in IWQOL-Lite total score than placebo patients (48.2%) (P < 0.001). Body mass index (BMI) reduction was the primary driver of improved HRQOL (P < 0.0001), with depressive symptoms and total cholesterol also playing a role (P < 0.05). Improved HRQOL varied by gender, age, race and presence of diabetes and other comorbidities. Lorcaserin treatment significantly improves HRQOL compared with placebo. Although BMI reduction accounts for the majority of these improvements, improvement in depressive symptoms and total cholesterol are contributing factors.

Topics: Adolescent; Adult; Aged; Anti-Obesity Agents; Benzazepines; Body Mass Index; Female; Humans; Male; Middle Aged; Obesity; Quality of Life; Weight Loss; Young Adult

Lorcaserin is a selective serotonin 2C receptor (5-HT2C) agonist approved in the United States for use in chronic weight management as an adjunct to a reduced-calorie diet and increased physical activity. Its pharmacologic activity is limited to 5-HT subtype 2 receptors. The potency of lorcaserin for the 5-HT2C receptor is 14-fold greater than its potency for the 5-HT2A receptor and 61-fold greater than its potency for the 5-HT2B receptor. Although 5-HT receptors have been implicated in serotonin syndrome, the precise pathogenesis is unknown. Given a theoretic risk for this syndrome in patients administered lorcaserin either alone or in combination with certain serotonergic agents (eg, selective serotonin reuptake inhibitors [SSRIs] and serotonin-norepinephrine reuptake inhibitors [SNRIs]), patients taking prohibited serotonergic agents were excluded from the Phase III clinical trials. This retrospective analysis evaluated the tolerability of lorcaserin in patients who took protocol-allowed or proscribed serotonergic agents for varying durations of up to 1 year during the BLOOM, BLOSSOM, and BLOOM-DM studies.. Patients randomly assigned to receive either lorcaserin 10 mg QD, lorcaserin 10 mg BID, or placebo and who took a spectrum of serotonergic agents were evaluated at week 52 of treatment (814 and 624 patients receiving lorcaserin and placebo, respectively, were found to have taken allowed or prohibited serotonergic agents during these trials). After the use of a proscribed serotonergic agent was discovered, these patients were discontinued from the trial and followed.. None of the patients in the serotonergic agent subpopulation or in the overall safety population met the clinical criteria of serotonin syndrome. The proportions of patients experiencing any adverse event (AE) were balanced in the lorcaserin and placebo groups in the prohibited serotonergic agent subpopulation. The prevalences of the most common AEs were similar between the serotonergic agent subpopulation and the overall safety population.. The concurrent use of lorcaserin and prohibited or allowed serotonergic agents did not appear to have increased the spectrum or intensity of AEs potentially associated with serotonin excess in this limited dataset. However, the sample population was too small to rule out an effect on a rare event such as serotonin syndrome. ClinicalTrials.gov identifiers: NCT00395135, NCT00603902, and NCT00603291.

Topics: Adult; Anti-Obesity Agents; Benzazepines; Drug Interactions; Female; Humans; Male; Middle Aged; Obesity; Overweight; Receptor, Serotonin, 5-HT2C; Retrospective Studies; Serotonin 5-HT2 Receptor Agonists; Serotonin Agents; Serotonin Syndrome; Weight Loss

Lorcaserin is a serotonin 5-hydroxytryptamine 2c receptor agonist effective in treating obesity. Studies in rodents have shown that lorcaserin acts in the brain to exert its weight-reducing effects, but this has not yet been studied in humans. We performed a randomized, placebo-controlled, double-blind trial with 48 obese participants and used functional MRI to study the effects of lorcaserin on the brain. Subjects taking lorcaserin had decreased brain activations in the attention-related parietal and visual cortices in response to highly palatable food cues at 1 week in the fasting state and in the parietal cortex in response to any food cues at 4 weeks in the fed state. Decreases in emotion- and salience-related limbic activity, including the insula and amygdala, were attenuated at 4 weeks. Decreases in caloric intake, weight, and BMI correlated with activations in the amygdala, parietal, and visual cortices at baseline. These data suggest that lorcaserin exerts its weight-reducing effects by decreasing attention-related brain activations to food cues (parietal and visual cortices) and emotional and limbic activity (insula, amygdala). Results indicating that baseline activation of the amygdala relates to increased efficacy suggest that lorcaserin would be of particular benefit to emotional eaters.

Topics: Anti-Obesity Agents; Benzazepines; Body Weight; Brain; Cues; Double-Blind Method; Emotions; Energy Intake; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Obesity; Weight Loss

Treatment guidelines for type 2 diabetes mellitus (T2DM) suggest weight loss as a means to maintain glycemic control. Lorcaserin has been approved for chronic weight management in the United States as an adjunct to a reduced-calorie diet and exercise, and the previous phase 3 Behavioral Modification and Lorcaserin for Obesity and Overweight Management in Diabetes Mellitus (BLOOM-DM) study has shown that, in addition to weight loss, lorcaserin is associated with improvements in glycemic parameters. In this post hoc analysis of the BLOOM-DM trial, the relationship between responder status (patients achieving ≥5% weight loss at Week 52) and glycemic and cardiometabolic parameters is evaluated.. Data are presented for patients receiving lorcaserin 10 mg twice daily or placebo for 52 weeks.. More than twice as many patients receiving lorcaserin plus diet and exercise counseling were classified as Week 52 responders compared to those receiving diet and exercise counseling alone (37.5% vs. 16.1%, respectively; p < 0.001), and lorcaserin Week 52 responders had greater improvements vs. placebo Week 52 responders in FPG (-38.1 mg/dL vs. -26.0 mg/dL) and HbA1c (-1.3% vs. -1.0%). Furthermore, more lorcaserin-treated Week 52 responders decreased the number of concomitant oral antidiabetic medications (OADs) used, and fewer increased the number of OADs used, compared to placebo. Unexpectedly, lorcaserin Week 52 nonresponders also had substantial reductions in glycemic levels, despite very modest weight loss.. These data support lorcaserin use in overweight and obese patients with T2DM to promote weight loss and facilitate glycemic control.. www.clinicaltrials.gov identifier is NCT00603291.

Topics: Adolescent; Adult; Aged; Benzazepines; Blood Glucose; Body Mass Index; Counseling; Diabetes Mellitus, Type 2; Diet; Double-Blind Method; Exercise; Female; Glycated Hemoglobin; Humans; Life Style; Male; Middle Aged; Obesity; Overweight; Racial Groups; Serotonin Receptor Agonists; Weight Loss; Young Adult

Lorcaserin is a serotonin 2C receptor agonist approved for chronic weight management. This analysis explores the number of patients needed to be treated (NNT) with lorcaserin for one more patient to achieve weight loss and glycemic goals.. This is a post hoc analysis of three Phase 3 studies in adults with and without type 2 diabetes mellitus (T2DM) treated with lorcaserin 10 mg BID or placebo. NNT is reported for patients achieving ≥5% or ≥10% weight loss, achievement of either HbA1c <5.7% or FPG <100 mg/dL in patients with prediabetes, and reduction of HbA1c to <7% in patients with T2DM at Week 52.. In the modified intention-to-treat (MITT) population, NNTs for ≥5% and ≥10% weight loss were 3.6 and 6.2 (without T2DM) and 4.3 and 7.5 (with T2DM); in Week 12 responders (≥5% weight loss at Week 12), NNTs were 1.7 and 2.6 (without T2DM) and 1.9 and 3.2 (with T2DM). In patients with prediabetes, NNTs to achieve HbA1c <5.7% were 9.9 (MITT) and 5.2 (Week 12 responders). In patients with T2DM, NNTs to achieve HbA1c <7% were 4.2 (MITT) and 2.3 (Week 12 responders).. In addition to weight management, lorcaserin improved glycemic control in patients with prediabetes and facilitated targeted HbA1c reduction in patients with T2DM, especially for those who achieved ≥5% weight loss by Week 12. Assessment of treatment response at Week 12 is a valuable tool to achieve efficient use of healthcare resources.. www.clinicaltrials.gov identifiers are NCT00395135, NCT00603291, and NCT00603902.

Topics: Adolescent; Adult; Aged; Benzazepines; Blood Glucose; Body Mass Index; Body Weight; Comorbidity; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Therapy, Combination; Exercise; Female; Humans; Hypoglycemic Agents; Male; Middle Aged; Obesity; Prediabetic State; Serotonin 5-HT2 Receptor Agonists; Weight Loss; Young Adult

To identify an early treatment milestone that optimizes sensitivity and specificity for predicting ≥5% weight loss at Week (W) 52 in patients with and without type 2 diabetes on lorcaserin or placebo.. Post hoc area under the curve for receiver operating characteristic analyses of data from three phase 3 trials comparing lifestyle modification+placebo with lifestyle modification+lorcaserin. A total of 6897 patients (18-65 years; BMI, 30-45 or 27-29.9 kg/m(2) with ≥1 comorbidity) were randomized to placebo or lorcaserin 10 mg bid. Changes (baseline to W52) in cardiometabolic parameters were assessed.. Response (≥5% weight loss from baseline) at W12 was a strong predictor of W52 response. Lorcaserin patients with a W12 response achieved mean W52 weight losses of 10.6 kg (without diabetes) and 9.3 kg (with diabetes). Proportions achieving ≥5% and ≥10% weight loss at W52 were 85.5% and 49.8% (without diabetes), and 70.5% and 35.9% (with diabetes). Lorcaserin patients who did not achieve a W12 response lost 3.2 kg (without diabetes) and 2.8 kg (with diabetes) at W52. Responders had greater improvements in cardiometabolic risk factors than the modified intent-to-treat (MITT) population, consistent with greater weight loss.. ≥5% weight loss by W12 predicts robust response to lorcaserin at 1 year.

Topics: Adolescent; Adult; Aged; Anti-Obesity Agents; Area Under Curve; Benzazepines; Diabetes Mellitus, Type 2; Diet; Exercise; Female; Humans; Life Style; Male; Middle Aged; Obesity; Outcome Assessment, Health Care; Weight Loss; Young Adult

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.. 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.. 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.. 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.

Topics: Adolescent; Adult; Aged; Anti-Obesity Agents; Benzazepines; Blood Glucose; Blood Pressure; Cholesterol, HDL; Cholesterol, LDL; Double-Blind Method; Female; Glycated Hemoglobin; Headache; Heart Rate; Humans; Life Style; Male; Middle Aged; Nasopharyngitis; Obesity; Quality of Life; Respiratory Tract Infections; Serotonin 5-HT2 Receptor Agonists; Triglycerides; Waist Circumference; Weight Loss; Young Adult

Lorcaserin is a selective 5-HT2C agonist evaluated for weight management in clinical trials. Echocardiographic monitoring was conducted to test the hypothesis that selective 5-HT2C agonism would avoid valvular heart disease.. Echocardiographic and weight change data from 5249 obese and overweight patients in 3 phase 3 trials were integrated. Treatment duration with 10 mg lorcaserin twice daily or placebo was 52 weeks. The proportions of patients who developed Food and Drug Administration-defined valvulopathy (≥ mild aortic or ≥ moderate mitral regurgitation) and changes in regurgitant grade at each heart valve were evaluated. Possible associations between weight or body mass index change and valvulopathy were explored. New valvulopathy was present in 2.04% of placebo and 2.37% of lorcaserin recipients at 52 weeks (risk difference, 0.33%; 95% confidence interval, -0.46 to 1.13; risk ratio, 1.16 [all patients with sufficient echocardiographic data, last-observation-carried-forward imputation] or 1.03 [patients who completed 52 weeks]). Changes in weight and body mass index were negatively associated with presence of valvulopathy at week 52 (P=0.02 and P=0.04, respectively); a 5% decrease in weight was associated with an odds ratio of 1.15 for Food and Drug Administration-defined valvulopathy. Most changes in regurgitation were ±1 grade in both treatment groups at all heart valves.. In 3 prospective placebo-controlled trials with integrated data for 5249 patients, the rate of echocardiographic valvulopathy was similar with lorcaserin and placebo. Point estimates for risk ratios ranged from 1.03 to 1.16 and may be at least partially influenced by greater weight loss in the lorcaserin group than in the placebo group.. URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00395135, NCT00603291, NCT00603902.

Topics: Adolescent; Adult; Aged; Anti-Obesity Agents; Aortic Valve Insufficiency; Benzazepines; Body Mass Index; Female; Humans; Male; Middle Aged; Mitral Valve Insufficiency; Obesity; Odds Ratio; Prospective Studies; Receptor, Serotonin, 5-HT2C; Risk Factors; Serotonin 5-HT2 Receptor Agonists; Severity of Illness Index; Time Factors; Treatment Outcome; Ultrasonography; Weight Loss; Young Adult

The BLOOM-DM (Behavioral Modification and Lorcaserin for Obesity and Overweight Management in Diabetes Mellitus) study evaluated efficacy and safety of lorcaserin for weight loss in patients with type 2 diabetes. Secondary objectives included evaluations of glycemic control, lipids, blood pressure, and quality of life. This 1-year, randomized, placebo-controlled trial enrolled 604 patients 1:1:1 to placebo, lorcaserin 10 mg once daily (QD) or lorcaserin 10 mg twice daily (BID). Patients were treated with metformin, a sulfonylurea (SFU) or both; had glycated hemoglobin (HbA(1c)) 7-10%; were 18-65 years old; and had BMI 27-45 kg/m(2). Patients received diet and exercise counseling. Safety monitoring included serial echocardiograms. Mean (± SD) age was 52.7 ± 8.7; 54.2% were women; 60.5% were white, 20.9% were African American, and 13.8% were Hispanic. Mean (± SD) weight was 103.6 ± 17.8 kg; BMI was 36.0 ± 4.5 kg/m(2). Most patients (91.7%) took metformin; 50.2% took a SFU. More patients lost ≥5% body weight with lorcaserin BID (37.5%; P < 0.001) or lorcaserin QD (44.7%; P < 0.001) vs. placebo (16.1%; modified intent to treat (MITT)/last observation carried forward (LOCF)). Least square mean (± SEM) weight change was -4.5 ± 0.35% with lorcaserin BID and -5.0 ± 0.5% with lorcaserin QD vs. -1.5 ± 0.36% with placebo (P < 0.001 for each). HbA(1c) decreased 0.9 ± 0.06 with lorcaserin BID, 1.0 ± 0.09 with lorcaserin QD, and 0.4 ± 0.06 with placebo (P < 0.001 for each); fasting glucose decreased 27.4 ± 2.5 mg/dl, -28.4 ± 3.8 mg/dl, and 11.9 ± 2.5 mg/dl, respectively (P < 0.001 for each). Symptomatic hypoglycemia occurred in 7.4% of patients on lorcaserin BID, 10.5% on lorcaserin QD, and 6.3% on placebo. Common adverse events were headache, back pain, nasopharyngitis, and nausea. Lorcaserin was associated with significant weight loss and improvement in glycemic control in patients with type 2 diabetes.

Topics: Adult; Aged; Anti-Obesity Agents; Benzazepines; Blood Glucose; Body Mass Index; Counseling; Diabetes Mellitus, Type 2; Double-Blind Method; Echocardiography; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Male; Middle Aged; Obesity; Quality of Life; Receptor, Serotonin, 5-HT2C; Risk Reduction Behavior; 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

Topics: Benzazepines; Humans; Neoplasms; United States; United States Food and Drug Administration; Weight Loss

Obesity and diabetes are major metabolic disorders that progress to severe morbidity and mortality. Neuroendocrine mechanisms controlling energy balance indicate that combination therapies are needed to sustain weight loss. Lorcaserin was one of the approved therapies for the treatment of obesity, which is recently withdrawn because a safety clinical trial, shows an increased occurrence of cancer. Coagonist of glucagon-like-peptide-1 (GLP-1) and glucagon receptors is a novel investigational therapy demonstrated to have both anti-obesity and anti-diabetic effect. Here, we investigated the effect of combination of lorcaserin and a GLP-1 and glucagon receptors coagonist in diet-induced obese (DIO) mice model.. The diet-induced obese C57BL/6J mice were used to assess acute and chronic effect of lorcaserin, coagonist of GLP-1and glucagon receptors and their combination on food intake, body weight, and biochemical parameters.. In acute study, combination of lorcaserin and coagonist causes synergistic reductions in food intake and body weight. Repeated treatment of combination of lorcaserin and coagonist showed enhanced body weight loss over time, which is due to reduction in fat mass (subcutaneous, retroperitoneal, mesenteric and epididymal fat pad) compared to individual therapy. Also, suppression of locomotor activity seen with lorcaserin was not evident in combination with coagonist. No additive effect was observed in glucose tolerance (intraperitoneal glucose tolerance test or insulin tolerance test), serum lipids, hepatic lipids, and energy expenditure in combination group.. These data suggest that combination of lorcaserin and coagonist could be a better combination to induce body weight loss.

Topics: Animals; Benzazepines; Body Weight; Diet, High-Fat; Energy Metabolism; Glucagon; Glucagon-Like Peptide 1; Glucose Tolerance Test; Liver; Male; Metabolic Diseases; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; Receptors, Glucagon; Weight Loss

The histamine 3 receptor (H3R) is a presynaptic receptor, which modulates several neurotransmitters including histamine and various essential physiological processes, such as feeding, arousal, cognition, and pain. The H3R is considered as a drug target for the treatment of several central nervous system disorders. We have synthesized and identified a novel series of 4-aryl-6-methyl-5,6,7,8-tetrahydroquinazolinamines that act as selective H3R antagonists. Among all the synthesized compounds, in vitro and docking studies suggested that the 4-methoxy-phenyl-substituted tetrahydroquinazolinamine compound 4c has potent and selective H3R antagonist activity (IC

Topics: Animals; Anti-Obesity Agents; Blood Glucose; Diet, High-Fat; HEK293 Cells; Histamine H3 Antagonists; Humans; Male; Mice, Inbred C57BL; Molecular Structure; Obesity; Proto-Oncogene Proteins c-fos; Quinazolines; Receptors, Histamine H3; Stereoisomerism; Structure-Activity Relationship; Weight Loss

Topics: Benzazepines; Camellia; Humans; Obesity; Overweight; Weight Loss

To compare the effectiveness of weight-management medications used to assist with weight loss in real-world clinical practice in the Veterans Health Administration (VHA).. Retrospective, multicenter, observational cohort study.. National VA Corporate Data Warehouse.. A total of 66,035 VA patients aged 18 years or older with a body mass index of 25 kg/m. The primary outcome was the percentage change in weight from baseline to at least 20 weeks or later (i.e., closest weight to 6 months). Secondary outcomes were difference in the percentage of weight loss at 12 and 36 weeks; changes in blood pressure, hemoglobin A. In the VA population, the effectiveness of four available weight-management medications was similar. Patients receiving phentermine-topiramate had a greater proportion of weight loss after at least 20 weeks compared with those solely enrolled in the VA's MOVE! weight-management program.

Topics: Adult; Aged; Anti-Obesity Agents; Benzazepines; Body Weight; Cohort Studies; Delayed-Action Preparations; Female; Humans; Male; Middle Aged; Obesity; Orlistat; Phentermine; Retrospective Studies; Topiramate; United States; United States Department of Veterans Affairs; Weight Loss

Topics: Benzazepines; Humans; Obesity; Overweight; Weight Loss

The increasing prevalence of type 2 diabetes (T2D) and associated morbidity and mortality emphasizes the need for a more complete understanding of the mechanisms mediating glucose homeostasis to accelerate the identification of new medications. Recent reports indicate that the obesity medication lorcaserin, a 5-hydroxytryptamine (5-HT, serotonin) 2C receptor (5-HT. Murine models of common and genetic T2D were utilized to probe the direct effect of lorcaserin on glycemic control.. Lorcaserin dose-dependently improves glycemic control in mouse models of T2D in the absence of reductions in food intake or body weight. Examining the mechanism of this effect, we reveal a necessary and sufficient neurochemical mediator of lorcaserin's glucoregulatory effects, brain pro-opiomelanocortin (POMC) peptides. To clarify further lorcaserin's therapeutic brain circuit, we examined the receptor target of POMC peptides. We demonstrate that lorcaserin requires functional melanocortin4 receptors on cholinergic preganglionic neurons (MC4R. These data suggest that lorcaserin's action within the brain represents a mechanistically novel treatment for T2D: findings of significance to a prevalent global disease.

Topics: Animals; Benzazepines; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Disease Models, Animal; Eating; Energy Metabolism; Glucose; Glucose Tolerance Test; Homeostasis; Humans; Insulin Resistance; Melanocortins; Mice; Mice, Transgenic; Obesity; Receptor, Serotonin, 5-HT2C; Receptors, Melanocortin; Weight Loss

Obesity is a chronic disease universally defined as an excess of adipose tissue resulting in body mass index (BMI) > 30.0 kg/m2. Over the past few years, the concept of prevention has gained increased awareness, thus leading to the development of additional pharmaceutical options for the treatment of obesity since 2012. Treating obesity revolves around an individualized, multi-disciplinary approach with additional focus on a healthy and supportive lifestyle to maintain the weight loss. [Full article available at http://rimed.org/rimedicaljournal-2017-03.asp].

Topics: Anti-Obesity Agents; Benzazepines; Body Mass Index; Bupropion; Drug Combinations; Fructose; Humans; Lactones; Liraglutide; Naltrexone; Obesity; Orlistat; Phentermine; Weight Loss

The recent approval of liraglutide, lorcaserin, naltrexone/bupropion extended-release, and phentermine/topiramate extended-release, brings the number of medications for long-term weight loss to 5 (including orlistat). Indicated for the treatment of patients with overweight (body mass index [BMI] ≥27 kg/m2 with ≥1 weight-related comorbidity) or obesity (BMI ≥30 kg/m2), these medications provide new opportunities to address this burgeoning health problem.

Topics: Anti-Obesity Agents; Benzazepines; Body Mass Index; Bupropion; Guidelines as Topic; Humans; Lactones; Life Style; Liraglutide; Naltrexone; Obesity; Orlistat; Overweight; Phentermine; Primary Health Care; Risk Factors; Treatment Outcome; Weight Loss

In 2012, the US Food and Drug Administration approved 2 drugs for long-term weight loss: lorcaserin hydrochloride (Belviq; Eisai Inc) and phentermine-topiramate (Qysmia; Vivus Inc). The approvals were based on 1-year trials showing that on top of recommendations to follow a calorie-restricted diet and to increase exercise, patients randomized to either drug lost more weight than patients randomized to placebo (3% [95% CI, 3%-4%] more weight lost with lorcaserin; 7% [95% CI, 3%-4%] more with phentermine /topiramate). The drugs have been associated with serious harms: Both drugs' labels include warnings about memory, attention, or language problems and depression; for lorcaserin, the label also warns of valvular heart disease and euphoria; and for phentermine-topiramate, the label warns of metabolic acidosis, increased heart rate, anxiety, insomnia, and elevated creatinine levels. Neither medication is marketed in Europe because of safety concerns. The manufacturer withdrew its application for lorcaserin in Europe after the European Medicines Agency (EMA) said approval was unlikely, and the EMA rejected phentermine-topiramate. In the United States, the required postmarketing safety trials are behind schedule. Until there is more convincing evidence about the cardiovascular safety of these drugs, physicians and patients should approach them cautiously. Patients who do not lose at least 5% of their body weight within 12 weeks of starting to take either drug should stop taking it, as stated in the prescribing information.

Topics: Anti-Obesity Agents; Benzazepines; Female; Fructose; Humans; Male; Obesity; Phentermine; Product Surveillance, Postmarketing; Randomized Controlled Trials as Topic; Topiramate; United States; United States Food and Drug Administration; Weight Loss

Treatment of obesity and overweight is based primarily on dietary measures and physical exercise.There are still no drugs with a favourable harm-benefit balance in this setting. Lorcaserin, a "selective" 5HT2C serotonin receptor agonist, has been refused marketing authorisation in the European Union despite approval in the United States. Clinical evaluation of lorcaserin is based on three placebo-controlled trials, each lasting one year, in a total of about 6000 patients. Two trials involved obese patients, and one obese patients with type 2 diabetes. The results of these trials are undermined by the large proportion (40% to 50%) of patients who were lost to follow-up before the end of the trial. None of the trials examined the impact of lorcaserin on the clinical complications of obesity. From an average initial weight of about 100 kg, patients taking lorcaserin lost only about 3 kg more than those in the placebo groups.The patients put on weight again after lorcaserin was discontinued. Adverse effects observed in clinical trials were mainly gastrointestinal (dry mouth, nausea) and neuropsychiatric (dizziness, fatigue, headache, euphoria). The incidence of cardiac valve disorders was higher with lorcaserin than with placebo. These trials were too short in duration to exclude a risk of cancer (breast cancer and astrocytoma) that was reported in experimental animals. This serotonin agonist is metabolised by the liver, creating a risk of multiple drug interactions. In practice, lorcaserin has not been shown to prevent complications of obesity or even lead to substantial weight loss.There is therefore no justification for exposing patients to the risk of adverse effects.

Topics: Anti-Obesity Agents; Benzazepines; Clinical Trials as Topic; Drug Approval; Humans; Obesity; Overweight; Weight Loss

Topics: Benzazepines; Bupropion; Drug Combinations; Drug Prescriptions; Fructose; Humans; Naltrexone; Obesity; Phentermine; Topiramate; Weight Loss

Topics: Animals; Anti-Obesity Agents; Benzazepines; Humans; Obesity; Serotonin 5-HT2 Receptor Agonists; Weight Loss

Topics: Appetite Depressants; Benzazepines; Drug Combinations; Fructose; Humans; Obesity; Overweight; Phentermine; Weight Loss

Topics: Appetite Depressants; Benzazepines; Drug Utilization; Fructose; Humans; Obesity; Phentermine; Prescription Drugs; Topiramate; United States; Weight Loss

Topics: Anti-Obesity Agents; Benzazepines; Bupropion; Cyclobutanes; Fructose; Humans; Naltrexone; Obesity; Phentermine; Risk Assessment; Risk Factors; Topiramate; Weight Loss

Topics: Adult; Anti-Obesity Agents; Benzazepines; Dose-Response Relationship, Drug; Drug Combinations; Drugs, Investigational; Female; Fructose; Heart Valve Diseases; Humans; Male; Obesity; Phentermine; Pregnancy; Tachycardia; Teratogens; Topiramate; Weight Loss

Topics: Appetite Depressants; Benzazepines; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Drug Approval; Humans; Obesity; Serotonin 5-HT2 Receptor Agonists; United States; United States Food and Drug Administration; Weight Loss

Topics: Anti-Obesity Agents; Benzazepines; Drug Combinations; Drug Interactions; Fructose; Humans; Obesity; Overweight; Phentermine; Receptor, Serotonin, 5-HT2C; Serotonin 5-HT2 Receptor Agonists; Treatment Outcome; Weight Loss

Efficacy of weight loss and maintenance therapies in obesity is difficult to quantify due to continuous weight changes over time. We assessed a single exponential model of weight changes during selected non-surgical therapies of non-diabetic obese subjects. We analyzed published mean weight data from 6 studies of ≥12 weeks duration, with comparable treatment groups, and ≥4 weight measurements during very low carbohydrate or fat diets, or treatment with Lorcaserin, Sibutramine or Orlistat. We fit data to a single exponential model to estimate maximum predicted weight loss or regain and duration of weight loss or regain for each therapy. A single exponential is the appropriate model as determined by Kolmogorov-Smirnov, constant variance, and Durbin-Watson tests. Validity of parameter estimates was indicated by coefficients of variation <25%. Sensitivity analysis showed that weight regain at the end of the weight loss phase affected parameter estimates in some instances, with variations of weight loss of 0.2-0.7% of basal. Estimated weight loss and regain were similar to observed weight changes in all studies. The model could also be used to assess dose-response relationships. Estimates from the model were used to compare concurrent obesity regimens using 95% confidence intervals, taking into account pre-determined minimal clinically important differences. This exponential model may provide accurate estimates of maximum achievable weight loss or regain and optimal duration of efficacy for a variety of non-surgical weight loss and maintenance regimens from published mean weight data and may be useful to more accurately evaluate weight loss and maintenance regimens.

Topics: Adult; Anti-Obesity Agents; Appetite Depressants; Benzazepines; Body Mass Index; Body Weight; Cyclobutanes; Diet Therapy; Female; Humans; Lactones; Male; Models, Theoretical; Obesity; Orlistat; Sensitivity and Specificity; Treatment Outcome; Weight Loss

Topics: Abnormalities, Drug-Induced; Anti-Obesity Agents; Benzazepines; Delayed-Action Preparations; Drug Approval; Drug Combinations; Female; Fructose; Humans; Obesity; Phentermine; Pregnancy; Serotonin Receptor Agonists; Topiramate; United States; United States Food and Drug Administration; Weight Loss

Topics: Adult; Benzazepines; Body Mass Index; Drug Approval; Female; Humans; Male; Middle Aged; Obesity; Overweight; Treatment Outcome; United States; United States Food and Drug Administration; Weight Loss

Topics: Anti-Obesity Agents; Benzazepines; Contraindications; Cyclobutanes; Drug Approval; Fenfluramine; Humans; Obesity; Overweight; Serotonin 5-HT2 Receptor Agonists; Serotonin Receptor Agonists; United States; United States Food and Drug Administration; Weight Loss

Topics: Adult; Anti-Obesity Agents; Appetite; Appetite Depressants; Appetite Regulation; Benzazepines; Humans; Obesity; Placebos; Randomized Controlled Trials as Topic; Risk Reduction Behavior; Serotonin Receptor Agonists; Treatment Outcome; Weight Loss

Topics: Anti-Obesity Agents; Benzazepines; Confidence Intervals; Confounding Factors, Epidemiologic; Heart Valve Diseases; Humans; Intention to Treat Analysis; Obesity; Overweight; Weight Loss

Topics: Anti-Obesity Agents; Benzazepines; Body Mass Index; Humans; Hypertension; Obesity; Overweight; Weight Loss

Topics: Anti-Obesity Agents; Benzazepines; Combined Modality Therapy; Humans; Obesity; Overweight; Patient Dropouts; Weight Loss