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The World Journal of Men's Health Apr 2021As a chronic and relapsing disease, obesity negatively impacts the health of men to a greater extent than that of women, with a higher risk of cardiovascular disease.... (Review)
Review
As a chronic and relapsing disease, obesity negatively impacts the health of men to a greater extent than that of women, with a higher risk of cardiovascular disease. Since lifestyle modifications alone are often challenging and limited for the maintenance of weight reduction, pharmacotherapy should be considered in a timely manner for obese men or overweight patients with weight-related comorbidities. Recent advances in anti-obesity drugs have enabled the potential of achieving clinically significant weight loss. Increasing evidence has shown that behavior-based interventions with one of these medications can result in greater weight loss than that elicited by usual care conditions. Data from most recent meta-analyses showed that the overall placebo-subtracted weight reduction (%) with the use of anti-obesity drugs for at least 12 months ranges from 2.9% to 6.8%; phentermine/topiramate (-6.8%) liraglutide (-5.4%), naltrexone/bupropion (-4.0%), lorcaserin (-3.1%), and orlistat (-2.9%). However, they have a high cost and may cause adverse outcomes depending on the individual. Very recently, on February 13, 2020, the US Food and Drug Administration requested withdrawal of lorcaserin from the market because a safety clinical trial showed an increased occurrence of cancer. Therefore the decision to initiate drug therapy in obese individuals should be made after the benefits and risks are considered. Thereafter, treatment should be tailored to specific patient subpopulations depending on their chronic conditions, comorbidities, and preferences. Herein, we provide an overview of the latest developments in weight loss medications, which may serve as one of the strategies for long-term obesity control.
PubMed: 32202085
DOI: 10.5534/wjmh.200010 -
CNS Drugs Mar 2022Dravet syndrome is a severe developmental and epileptic encephalopathy characterised by refractory seizures and cognitive dysfunction. The treatment is challenging, not...
Dravet syndrome is a severe developmental and epileptic encephalopathy characterised by refractory seizures and cognitive dysfunction. The treatment is challenging, not least because the seizures are highly drug resistant, requiring multiple anti-seizure medications (ASMs), while some ASMs can exacerbate seizures. Initial treatments include the broad-spectrum ASMs valproate (VPA), and clobazam (CLB) in some regions; however, they are generally insufficient to control seizures. With this in mind, three adjunct ASMs have been approved specifically for the treatment of seizures in patients with Dravet syndrome: stiripentol (STP) in 2007 in the European Union and 2018 in the USA, cannabidiol (CBD) in 2018/2019 (in combination with CLB in the European Union) and fenfluramine (FFA) in 2020. These "add-on" therapies (mostly to VPA/CLB) are used as escalation therapies, with the choice dependent on availability in different countries, patient characteristics and caregiver preferences. Topiramate is also frequently used, with evidence of efficacy in Dravet syndrome, and there is anecdotal evidence of efficacy with bromide, which is frequently used in Germany and Japan. With a growing treatment landscape for Dravet syndrome, there can be practical challenges for clinicians, particularly with issues associated with polypharmacy. This practical guide provides an overview of these main ASMs including their indications/contraindications, mechanism of action, efficacy, safety and tolerability profile, dosage requirements, and laboratory and clinical parameters to be evaluated. Standard laboratory and clinical parameters include blood counts, liver function tests, serum concentrations of ASMs, monitoring the growth of children, as well as weight loss and acceleration of behavioural problems. Regular cardiac monitoring is also important with FFA as it has previously been associated with cases of cardiac valve disease when used in adults at high doses (up to 120 mg/day) in combination with phentermine as a therapy for obesity. Importantly, no signs of heart valve disease have been documented to date at the low doses used in patients with developmental and epileptic encephalopathies. In addition, potential drug-drug interactions and their consequences are a key consideration in everyday practice. Interactions that potentially require dosage adjustments to alleviate adverse events include the following: STP + CLB resulting in increased plasma concentrations of CLB and its active metabolite norclobazam may increase somnolence, and an interaction with STP and VPA may increase gastrointestinal adverse events. Cannabidiol has a bi-directional interaction with CLB producing an increase in plasma concentrations of 7-OH-CBD and norclobazam resulting in the potential for increased somnolence and sedation. In addition, CBD is associated with elevations of liver transaminases particularly in patients taking concomitant VPA. The interaction between FFA and STP requires a dose reduction of FFA. Furthermore, concomitant administration of VPA with topiramate has been associated with encephalopathy and/or hyperammonaemia. Finally, we briefly describe other ASMs used in Dravet syndrome, and current key clinical trials.
Topics: Adult; Anticonvulsants; Cannabidiol; Child; Clobazam; Drug Therapy, Combination; Epilepsies, Myoclonic; Epileptic Syndromes; Fenfluramine; Humans; Sleepiness; Spasms, Infantile; Topiramate
PubMed: 35156171
DOI: 10.1007/s40263-022-00898-1 -
Obesity Reviews : An Official Journal... Nov 2021Anti-obesity medications (AOMs) are efficacious and well tolerated in randomized controlled trials, but findings may not be generalizable to routine clinical practice.... (Review)
Review
Anti-obesity medications (AOMs) are efficacious and well tolerated in randomized controlled trials, but findings may not be generalizable to routine clinical practice. This systematic literature review aimed to identify real-world (RW) evidence for AOMs to treat adults ( ≥ 18 years) with obesity or overweight (BMI ≥ 27 kg/m ). Searches conducted in MEDLINE, Embase, Health Technology Assessment (HTA) Database, National Health Service (NHS) Economic Evaluation Database, and Cochrane Central Register of Controlled Trials for studies of relevant FDA-approved AOMs yielded 41 publications. Weight loss (WL) was consistently observed, with 14% to 58.6% of patients achieving ≥ 5% WL on orlistat, phentermine/topiramate, naltrexone/bupropion, phentermine, or liraglutide in studies of 3-6 months' duration where this was measured. When cardiometabolic risk factors were assessed, AOMs reduced or had no impact on blood pressure, lipids, or glycemia. RW data on the impact of AOMs on existing obesity-related comorbidities and mortality were generally lacking. AOMs were associated with various adverse events, but these were of mild to moderate severity and no unexpected safety signals were reported. A pattern of poor adherence and persistence with AOMs was observed across studies. Overall, the review confirmed the effectiveness of AOMs in RW settings but demonstrated large gaps in the evidence base.
Topics: Adult; Anti-Obesity Agents; Humans; Orlistat; Phentermine; State Medicine; Weight Loss
PubMed: 34423889
DOI: 10.1111/obr.13326 -
Journal of Managed Care & Specialty... Jul 2022The rising prevalence and associated public health burden of obesity has led to advancements in pharmaceuticals for weight management. Semaglutide 2.4 mg, an...
The rising prevalence and associated public health burden of obesity has led to advancements in pharmaceuticals for weight management. Semaglutide 2.4 mg, an anti-obesity medication (AOM) recently approved by the US Food and Drug Administration, has demonstrated clinically relevant weight loss in its phase 3 clinical trials. Economic evaluation comparing semaglutide 2.4 mg with other available weight management therapies is essential to inform payers for decision-making. To assess the cost-effectiveness of semaglutide 2.4 mg in the treatment of adult patients with obesity (ie, body mass index [BMI] ≥ 30) and adult patients who are overweight (ie, BMI 27-29.9) with 1 or more weight-related comorbidities from a US third-party payer perspective. A cohort Markov model was constructed to compare semaglutide 2.4 mg with the following comparators: no treatment, diet and exercise (D&E), and 3 branded AOMs (liraglutide 3 mg, phentermine-topiramate, and naltrexone-bupropion). All AOMs, including semaglutide 2.4 mg, were assumed to be taken in conjunction with D&E. Changes in BMI, blood pressure, cholesterol level, experience of acute and chronic obesity-related complications, costs, and quality-adjusted life years (QALYs) were simulated over 30 years based on pivotal trials of the AOMs and other relevant literature. Drug and health care prices reflect 2021 standardized values. Cost-effectiveness was examined with a willingness-to-pay (WTP) threshold of $150,000 per QALY gained. Sensitivity analyses were conducted to test the robustness of the cost-effectiveness results to plausible variation in model inputs. In the base-case analysis, treatment with semaglutide 2.4 mg was estimated to improve QALYs by 0.138 to 0.925 and incur higher costs by $3,254 to $25,086 over the 30-year time horizon vs comparators. Semaglutide 2.4 mg is cost-effective against all comparators at the prespecified WTP threshold, with the incremental cost per QALY gained ranging from $23,556 to $144,296 per QALY gained. In the sensitivity analysis, extended maximum treatment duration, types of subsequent treatment following therapy discontinuation, and weight-rebound rates were identified as key drivers for model results. The estimated probability of semaglutide 2.4 mg being cost-effective compared with comparators ranged from 67% to 100% when varying model parameters and assumptions. As a long-term weight management therapy, semaglutide 2.4 mg was estimated to be cost-effective compared with no treatment, D&E alone, and all other branded AOM comparators under a WTP threshold of $150,000 per QALY gained over a 30-year time horizon. Financial support for this research was provided by Novo Nordisk Inc. The study sponsor was involved in several aspects of the research, including the study design, the interpretation of data, the writing of the manuscript, and the decision to submit the manuscript for publication. Dr Kim and Ms Ramasamy are employees of Novo Nordisk Inc. Ms Kumar and Dr Burudpakdee were employees of Novo Nordisk Inc at the time this study was conducted. Dr Sullivan received research support from Novo Nordisk Inc for this study. Drs Wang, Song, Wu, Ms Xie, and Ms Sun are employees of Analysis Group, Inc, who received consultancy fees from Novo Nordisk Inc in connection with this study.
Topics: Adult; Cost-Benefit Analysis; Glucagon-Like Peptides; Humans; Obesity; Overweight; Quality-Adjusted Life Years; United States
PubMed: 35737858
DOI: 10.18553/jmcp.2022.28.7.740 -
Paediatric Drugs Nov 2022Phentermine/topiramate extended-release capsule (Qsymia) is a fixed-dose combination of phentermine and topiramate, which is being developed by VIVUS (a subsidiary of... (Review)
Review
Phentermine/topiramate extended-release capsule (Qsymia) is a fixed-dose combination of phentermine and topiramate, which is being developed by VIVUS (a subsidiary of Icahn Enterprises) for the treatment of obesity, sleep apnoea syndrome, type 2 diabetes mellitus and non-alcoholic steatohepatitis (NASH). The once-daily formulation of phentermine (a sympathomimetic amine) and topiramate is designed to combat obesity by decreasing appetite and increasing satiety. In July 2022, phentermine/topiramate received its first approval in the USA, as an adjunct to a reduced-calorie diet and increased physical activity, for chronic weight management in pediatric patients aged ≥ 12 years with BMI in the 95th percentile or greater standardized for age and sex. Phentermine/topiramate is approved in the US and South Korea for obesity in adults. Clinical development of phentermine/topiramate for sleep apnoea syndrome and type-2 diabetes in obese patients and preclinical development for NASH is ongoing in the US. This article summarizes the milestones in the development of phentermine/topiramate leading to this pediatric first approval for chronic weight management in adolescents.
Topics: Adult; Adolescent; Humans; Child; Topiramate; Anti-Obesity Agents; Sympathomimetics; Delayed-Action Preparations; Non-alcoholic Fatty Liver Disease; Diabetes Mellitus, Type 2; Weight Loss; Phentermine; Obesity; Fructose; Sleep Apnea Syndromes
PubMed: 36059008
DOI: 10.1007/s40272-022-00532-z -
Nutrition, Metabolism, and... Jun 2023To determine the cost-effectiveness of anti-obesity medications (AOM): tirzepatide, semaglutide, liraglutide, phentermine plus topiramate (PpT), and naltrexone plus...
BACKGROUND AND AIMS
To determine the cost-effectiveness of anti-obesity medications (AOM): tirzepatide, semaglutide, liraglutide, phentermine plus topiramate (PpT), and naltrexone plus bupropion (NpB).
METHODS AND RESULTS
From a U.S. perspective we developed a Markov model to simulate weight change over a 40-year time horizon using results from clinical studies. According to the body mass index (BMI), cardiovascular diseases, diabetes and mortality risk were the health states considered in the model, being mutually exclusive. Costs of AOM, adverse events, cardiovascular events, and diabetes were included. We applied a 3% per-year discount rate and calculated the incremental cost-effectiveness ratios (ICERs) of cost per quality-adjusted life-year (QALY) gained. Probabilistic sensitivity analyses incorporated uncertainty in input parameters. A deterministic analysis was conducted to determine the robustness of the model. The model included a cohort of 78.2% females with a mean age of 45 years and BMI of 37.1 (SD 4.9) for females and 36.8 (SD 4.9) for males. NpB and PpT were the least costly medications and, all medications differed no more than 0.5 QALYs. Tirzepatide ICER was $355,616 per QALY. Liraglutide and semaglutide options were dominated by PpT.
CONCLUSION
Compared to other AOM, PpT was lowest cost treatment with nearly identical QALYs with other agents.
Topics: Male; Female; Humans; Middle Aged; Cost-Effectiveness Analysis; Liraglutide; Cost-Benefit Analysis; Quality-Adjusted Life Years; Anti-Obesity Agents
PubMed: 37088648
DOI: 10.1016/j.numecd.2023.03.012 -
FP Essentials May 2020Pharmacotherapy, adjunctively with lifestyle interventions, is an option for any patient diagnosed with obesity (ie, body mass index [BMI] of 30 kg/m or greater) or with...
Pharmacotherapy, adjunctively with lifestyle interventions, is an option for any patient diagnosed with obesity (ie, body mass index [BMI] of 30 kg/m or greater) or with a BMI of 27 kg/m or greater and at least one coexisting condition, including type 2 diabetes, hypertension, hyperlipidemia, and sleep apnea. If the appropriate criteria are met, pharmacotherapy should be initiated for patients with overweight or obesity if lifestyle modification does not produce adequate weight loss. Lifestyle modifications should be continued and emphasized throughout treatment because it has been shown that adjunctive pharmacotherapy produces greater weight loss and weight loss maintenance than lifestyle interventions alone. Currently, five drugs are approved for weight management in adults: phentermine, orlistat, phentermine-topiramate, bupropion-naltrexone, and liraglutide. Certain drugs are approved for short-term management while others are approved for long-term management. Drug therapy should be customized to the individual patient, depending on needs, contraindications, and cost. Benefits of these drugs should be assessed regularly and a different drug should be considered if at least 5% of body weight is not lost by 3 months of therapy.
Topics: Adult; Anti-Obesity Agents; Benzazepines; Diabetes Mellitus, Type 2; Humans; Obesity; Phentermine
PubMed: 32383845
DOI: No ID Found