topiramate and lorcaserin

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

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

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

Obesity management requires a multidisciplinary approach, as there are many factors that contribute to the development of obesity, as well as the preservation of excess weight once it has been gained. Diet, exercise, and behavior modification are key components of treatment. In addition to lifestyle changes, weight gain secondary to medications is an important modifiable risk factor. Even after appropriate lifestyle modification, and medication adjustments (where possible) to avoid agents that can contribute to weight gain, many patients are still unable to achieve clinically meaningful weight loss. Pharmacotherapy for obesity management can fill an important role for these patients. This article will review medications that can lead to weight gain and potential alternatives, currently approved anti-obesity medications and best practices to individualize the selection process, and the use of testosterone in men with hypogonadism and obesity.

Topics: Androgens; Anti-Obesity Agents; Antidepressive Agents; Antihypertensive Agents; Antipsychotic Agents; Appetite Depressants; Benzazepines; Bupropion; Drug Combinations; Fructose; Humans; Hypoglycemic Agents; Hypogonadism; Lactones; Liraglutide; Naltrexone; Obesity; Orlistat; Phentermine; Testosterone; Topiramate; Weight Gain

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

Obesity is a growing epidemic and a major contributor to the global burden of disease. Obesity strains the healthcare systems and has profound economic and psychosocial consequences. Historically, pharmacotherapy for obesity has witnessed the rise and fall of several promising drug candidates that had to be eventually withdrawn due to unacceptable safety concerns. Currently four drugs are approved for chronic weight management in obese adults: orlistat, lorcaserin, phentermine/topiramate extended release and naltrexone/bupropion extended release. While lorcaserin and phentermine/topiramate were approved by US Food and Drug Administration (FDA) in 2012, after a gap of 13 years following the licensing of orlistat, naltrexone/bupropion has been recently approved in 2014. This review provides a brief overview of these current therapeutic interventions available for management of obesity along with the evidence of their safety and efficacy. Additionally, several novel monotherapies as well as combination products are undergoing evaluation in various stages of clinical development. These therapies if proven successful will strengthen the existing armamentarium of antiobesity drugs and will be critical to combat the global public health crisis of obesity and its associated co-morbidities.

Topics: Anti-Obesity Agents; Benzazepines; Bupropion; Drug Combinations; Drug Therapy, Combination; Fructose; Humans; Lactones; Naltrexone; Obesity; Orlistat; Phentermine; Topiramate

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

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

Topics: Anti-Obesity Agents; Appetite; Appetite Depressants; Benzazepines; Benzoxazines; Bupropion; Clinical Trials as Topic; Drug Approval; Drug Combinations; Drug Discovery; Energy Metabolism; Enzyme Inhibitors; Fructose; Glucagon-Like Peptide 1; Humans; Hypothalamus; Lactones; Lipase; Liraglutide; Metabolic Syndrome; Naltrexone; Obesity; Orlistat; Phentermine; Topiramate

Obesity is quickly becoming the leading preventable cause of death in the USA. Over 60 obesity-related comorbidities exist which increase the complexity and cost of medical care in obese patients. Even a moderate weight loss of 5 % can reduce morbidity associated with these conditions. Lifestyle modification through caloric restriction and enhanced exercise and physical activity remain the first line treatment for obesity. The development of pharmacologic agents for the treatment of obesity has been challenged by both lack of efficacy and serious adverse side effects leading to their removal from market. Two new agents were recently approved by the US Food and Drug Administration to complement lifestyle modification in obese (BMI ≥30 kg/m(2)) and overweight patients (BMI ≥27 kg/m(2) and one obesity-related comorbidity). Lorcaserin is a novel serotonin 5-HT2C selective agonist which has been shown in three phase III studies to significantly reduce weight and cardiovascular risk factors such as diabetes. Phentermine/topiramate extended release (ER) is a novel combination of two agents which have individually been shown to significantly reduce weight. The combination agent phentermine/topiramate ER has been shown to reduce weight in overweight and obese subjects in a number of studies. This article reviews the pharmacology, clinical efficacy, and safety of these new agents compared to past and other presently available medications for the treatment of obesity.

Topics: Anti-Obesity Agents; Benzazepines; Drug Approval; Drug Combinations; Fructose; Humans; Obesity; Phentermine; Topiramate; Treatment Outcome

Worldwide obesity prevalence has nearly doubled since 1980. Due to numerous co-morbidities, obesity represents a serious health and socioeconomic problem worldwide. Pharmacotherapy should be an integral part of comprehensive obesity management. Drug therapy can assist in weight loss and its maintenance in those individuals who do not achieve appropriate weight loss through lifestyle interventions alone. After the withdrawal of sibutramine from the market in 2010, orlistat, a lipase inhibitor, was the only remaining prescription drug approved for the long-term treatment of obesity. In 2012, phentermine/topiramate extended-release (PHEN/TPM ER) combination and lorcaserin were approved by the US FDA as novel medications for long-term weight management. Three major phase III trials conducted with each drug confirmed their efficacy in terms of weight loss/maintenance and improvement of cardiometabolic risks. No head-to-head studies between the two new anti-obesity drugs have been carried out. However, in the existing studies PHEN/TPM ER had a superior weight loss profile to lorcaserin but the incidence of adverse effects was lower with lorcaserin. Both drugs were well-tolerated, and adverse events were modest in intensity, dose dependent, rather rare, and tended to decrease with the duration of treatment. Major safety concerns regarding PHEN/TPM ER include elevations in resting pulse rate, teratogenicity, mild metabolic acidosis, and psychiatric and cognitive adverse events. Valvulopathy, cognitive impairment, psychiatric disorders, and hypoglycemia represent major safety concerns for lorcaserin. Although existing trials have not demonstrated any significant issues with PHEN/TPM ER-induced heart rate elevation and lorcaserin-induced valvulopathy, all safety concerns should be seriously taken into account in patients treated with either of these novel anti-obesity medications.

Topics: Anti-Obesity Agents; Benzazepines; Benzoxazines; Bupropion; Chemistry, Pharmaceutical; Drug-Related Side Effects and Adverse Reactions; Fructose; Glucagon-Like Peptide 1; Humans; Liraglutide; Naltrexone; Obesity; Phentermine; Topiramate

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

Topics: Adult; Aged; Anti-Obesity Agents; Appetite Depressants; Bariatric Surgery; Benzazepines; Fructose; Humans; Lactones; Middle Aged; Obesity; Orlistat; Phentermine; Topiramate

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

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

Obesity is a world-wide epidemic associated with significant morbidity and mortality which costs billions of dollars per year. The associated related conditions are many and include heart disease, stroke, type II diabetes mellitus, sleep apnea and certain types of cancer. Given that it is a multifactorial problem, the treatments must also address the numerous causes associated with the development of obesity. The neurohormonal regulation of feeding and energy is a complex system often necessitating modification through more than 1 pathway to achieve weight loss. Therefore, in addition to lifestyle changes, attenuation of caloric intake and increase in caloric expenditure, pharmacotherapies, including combination medications, may prove beneficial in its treatment. Adding to the current available pharmacotherapies for obesity, the Food and Drug Administration has recently approved 2 new combination medications known as lorcaserin (Belviq) and phentermine-topiramate (Qsymia). As with these and other medications used for weight loss, clinical cautions, side effects, precise review of patients' medical history and selecting the appropriate medication are imperative. Additionally, close follow-up is necessary in patients undergoing treatment for weight loss. As weight loss progresses, patients who are currently undergoing concomitant treatment for comorbid diabetes and hypertension need to be monitored for appropriate changes in medications used to treat those conditions. Weight loss is often accompanied by improvement in blood pressure and glucose levels and therefore resting blood pressure and fasting and/or postprandial plasma glucose levels should be monitored at follow-up. Although unique to each individual, the benefits of weight loss are substantial and can improve well-being and physical health.

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

Obesity, which results from an imbalance between calorie intake and expenditure, now affects over 500 million individuals worldwide. Lifestyle and behavioural interventions aimed at reducing calorie intake and/or increasing energy expenditure have limited long-term effectiveness due to complex and persistent hormonal, metabolic and neurochemical adaptations that defend against weight loss and promote weight regain. Surgical treatments for obesity, although highly effective, are unavailable or unsuitable for the majority of individuals with excess adiposity. Accordingly, few effective treatment options are available to most individuals with obesity. In the past, the use of antiobesity drugs, seemingly the logical choice to fill this therapeutic gap, has been limited because of a lack of efficacy, poor long-term adherence rates and serious adverse effects. In 2012, the FDA approved two new medications-lorcaserin and phentermine-topiramate controlled release-and is currently reviewing the resubmission of naltrexone sustained release-bupropion sustained release. This Review presents the available data on the efficacy and safety of these three medications and discusses future perspectives and challenges related to pharmacological weight management.

Topics: Appetite Depressants; Benzazepines; Drug Combinations; Fructose; Humans; Life Style; Obesity; Phentermine; Topiramate

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

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

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

Obesity 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

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

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

To highlight the prevalence and impact of obesity in the United States and provide nurse practitioners (NPs) with an overview of pharmacotherapy options for treatment of overweight and obese individuals.. A comprehensive review of the literature was conducted using multiple databases, including PubMed, MEDLINE, and Ovid. Keywords used to obtain relevant articles included obesity and drug, or orlistat, topiramate/phentermine, lorcaserin, bupropion/naltrexone, and liraglutide.. Obesity is a prevalent disease with more than two thirds of Americans being considered overweight and one third being obese. Obesity places patients at an increased risk for many comorbidities that impact patient health as well as public health. There are currently five approved medications for the chronic management of obesity, two of which were approved in 2014. These pharmacological therapies are options to aid weight loss in patients that are obese or those who are overweight with additional risk factors.. NPs can assist patients struggling with their weight. With new pharmacotherapy options, there is an opportunity to add to diet and exercise in order to achieve increased weight loss. A decrease in obesity would potentially alleviate the burden on the healthcare system, both socially and economically, and improve patient quality of life.

Topics: Benzazepines; Bupropion; Disease Management; Fructose; Humans; Lactones; Liraglutide; Naltrexone; Obesity; Orlistat; Phentermine; Topiramate; United States

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

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

Topics: Anti-Obesity Agents; Appetite Depressants; Benzazepines; Bupropion; Clinical Trials as Topic; Drug Approval; Drug Combinations; Europe; Fructose; Humans; Naltrexone; Obesity; Phentermine; Product Surveillance, Postmarketing; Topiramate; United States; United States Food and Drug Administration

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: 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: Anti-Obesity Agents; Benzazepines; Body Mass Index; Drug Approval; Drug Combinations; Fructose; Humans; Obesity; Phentermine; Topiramate; United States; United States Food and Drug Administration

Topics: Anti-Obesity Agents; Benzazepines; Drug Approval; Drug Combinations; Drug Evaluation, Preclinical; Fructose; Humans; Phentermine; Topiramate; United States; United States Food and Drug Administration