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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 -
The Medical Clinics of North America Jan 2018Although diet, physical activity, and behavioral modifications are the cornerstones of weight management, weight loss achieved by lifestyle modifications alone is often... (Review)
Review
Although diet, physical activity, and behavioral modifications are the cornerstones of weight management, weight loss achieved by lifestyle modifications alone is often limited and difficult to maintain. Pharmacotherapy for obesity can be considered if patients have a body mass index (BMI) of 30 kg/m or greater or BMI of 27 kg/m or greater with weight-related comorbidities. The 6 most commonly used antiobesity medications are phentermine, orlistat, phentermine/topiramate extended release, lorcaserin, naltrexone sustained release (SR)/bupropion SR, and liraglutide 3.0 mg. Successful pharmacotherapy for obesity depends on tailoring treatment to patients' behaviors and comorbidities and monitoring of efficacy, safety, and tolerability.
Topics: Anti-Obesity Agents; Benzazepines; Drug Combinations; Fructose; Humans; Lactones; Naltrexone; Obesity; Orlistat; Phentermine; Topiramate
PubMed: 29156182
DOI: 10.1016/j.mcna.2017.08.010 -
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 -
Obesity (Silver Spring, Md.) Apr 2019The aim of this work was to study weight loss and risk of cardiovascular disease (CVD) or death associated with longer-term phentermine use.
OBJECTIVE
The aim of this work was to study weight loss and risk of cardiovascular disease (CVD) or death associated with longer-term phentermine use.
METHODS
Using electronic health record data, 13,972 adults were identified with a first phentermine fill in 2010 to 2015, creating exposure categories according to a patient's duration of use (referent: ≤ 3 months). Multivariable linear models were used to compare percent weight loss across categories at 6, 12, and 24 months, and Cox proportional hazards models were used to compare risk of composite CVD or death, up to 3 years after starting phentermine.
RESULTS
The cohort was 84% female and 45% white, with a mean (SD) baseline age 43.5 (10.7) years and BMI of 37.8 (7.2) kg/m . In multivariable models, longer-term users of phentermine experienced more weight loss; patients using continuously for > 12 months lost 7.4% more than the referent group at 24 months (P < 0.001). The composite CVD or death outcome was rare (0.3%, 41 events), with no significant difference in hazard ratios between groups.
CONCLUSIONS
Greater weight loss without increased risk of incident CVD or death was observed in patients using phentermine monotherapy for longer than 3 months. Despite the limitations of the observational design, this study supports the effectiveness and safety of longer-term phentermine use for low-risk individuals.
Topics: Adolescent; Adult; Anti-Obesity Agents; Cardiovascular Diseases; Cause of Death; Cohort Studies; Electronic Health Records; Female; Humans; Male; Middle Aged; Mortality; Obesity; Phentermine; Retrospective Studies; Risk Factors; Time Factors; Treatment Outcome; United States; Weight Loss; Young Adult
PubMed: 30900410
DOI: 10.1002/oby.22430 -
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 -
Current Opinion in Lipidology Dec 2015The prevalence of obesity across the world continues to climb, bringing with it otherwise preventable obesity-related comorbidities including type 2 diabetes,... (Review)
Review
PURPOSE OF REVIEW
The prevalence of obesity across the world continues to climb, bringing with it otherwise preventable obesity-related comorbidities including type 2 diabetes, hypertension and cardiovascular disease. Weight loss is difficult to achieve and maintain through lifestyle interventions alone, leading to intense efforts to develop adjunctive pharmacological approaches. Herein, we examine recent advances in this field and limitations of currently available and emerging agents.
RECENT FINDINGS
Liraglutide, lorcaserin and combination of phentermine-topiramate and bupropion-naltrexone have all been the subject of recent studies examining their efficacy as weight-loss agents. Although each effectively induces weight loss over and above placebo, significant concerns exist regarding side-effect profiles and safety, along with their ability to achieve sustained effects. Dropout rates in all examined studies were up to 50% or more, usually a result of intolerable side-effects. Recruitment of a high proportion of women of European descent also casts doubt on the generalizability of trial data.
SUMMARY
Pharmacological interventions for weight loss remain limited, with side-effects often outweighing efficacy. Interestingly, substantial early weight loss was associated with sustained loss, suggesting a responsive phenotype and future trials might best be targeted in identifying responsive subpopulations.
Topics: Animals; Anti-Obesity Agents; Clinical Trials as Topic; Drug Discovery; Humans; Obesity
PubMed: 26382553
DOI: 10.1097/MOL.0000000000000232 -
Lancet (London, England) Apr 2024Pharmacotherapy provides an option for adults with overweight and obesity to reduce their bodyweight if lifestyle modifications fail. We summarised the latest evidence... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pharmacotherapy provides an option for adults with overweight and obesity to reduce their bodyweight if lifestyle modifications fail. We summarised the latest evidence for the benefits and harms of weight-lowering drugs.
METHODS
This systematic review and network meta-analysis included searches of PubMed, Embase, and Cochrane Library (CENTRAL) from inception to March 23, 2021, for randomised controlled trials of weight-lowering drugs in adults with overweight and obesity. We performed frequentist random-effect network meta-analyses to summarise the evidence and applied the Grading of Recommendations Assessment, Development, and Evaluation frameworks to rate the certainty of evidence, calculate the absolute effects, categorise interventions, and present the findings. The study was registered with PROSPERO, CRD 42021245678.
FINDINGS
14 605 citations were identified by our search, of which 132 eligible trials enrolled 48 209 participants. All drugs lowered bodyweight compared with lifestyle modification alone; all subsequent numbers refer to comparisons with lifestyle modification. High to moderate certainty evidence established phentermine-topiramate as the most effective in lowering weight (odds ratio [OR] of ≥5% weight reduction 8·02, 95% CI 5·24 to 12·27; mean difference [MD] of percentage bodyweight change -7·98, 95% CI -9·27 to -6·69) followed by GLP-1 receptor agonists (OR 6·33, 95% CI 5·00 to 8·00; MD -5·79, 95% CI -6·34 to -5·25). Naltrexone-bupropion (OR 2·69, 95% CI 2·10 to 3·44), phentermine-topiramate (2·40, 1·68 to 3·44), GLP-1 receptor agonists (2·22, 1·74 to 2·84), and orlistat (1·71, 1·42 to 2·05) were associated with increased adverse events leading to drug discontinuation. In a post-hoc analysis, semaglutide, a GLP-1 receptor agonist, showed substantially larger benefits than other drugs with a similar risk of adverse events as other drugs for both likelihood of weight loss of 5% or more (OR 9·82, 95% CI 7·09 to 13·61) and percentage bodyweight change (MD -11·40, 95% CI -12·51 to -10·29).
INTERPRETATION
In adults with overweight and obesity, phentermine-topiramate and GLP-1 receptor agonists proved the best drugs in reducing weight; of the GLP-1 agonists, semaglutide might be the most effective.
FUNDING
1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University.
Topics: Adult; Humans; Overweight; Network Meta-Analysis; Topiramate; Obesity; Weight Loss; Phentermine; Randomized Controlled Trials as Topic
PubMed: 38582569
DOI: 10.1016/S0140-6736(24)00351-9