Cost-effectiveness analysis of once-weekly semaglutide vs. once-daily liraglutide administered subcutaneously in patients with overweight and obesity: a decision analysis.

OBJECTIVE: Obesity presents an enduring and multifaceted dilemma that impacts individuals, society, economies, and healthcare systems alike. Glucagon-like peptide-1 (GLP-1) receptor agonists, including liraglutide and semaglutide, have received FDA approval for obesity treatment. This study aims to present a cost-effectiveness analysis to compare the cost and clinical outcomes of semaglutide vs. liraglutide on weight loss in people with overweight and obesity. MATERIALS AND METHODS: A cost-effectiveness analysis was conducted to compare the cost and the clinical outcomes of adding weekly 2.4 mg SC semaglutide vs. daily 3.0 mg SC liraglutide or placebo to physical activity and diet control in overweight and obese patients. A clinical outcome of achieving ≥15% weight loss was chosen. A simple decision analysis model from a third-payer perspective was applied. Drug costs were based on the retail price of the USA market. One-way sensitivity analyses were performed. RESULTS: Results showed that 2.4 mg weekly semaglutide, when added to physical activity and diet control, was the most cost-effective choice in terms of ≥15% weight loss (ICER: $ 7,056/patient/68 weeks). The model was robust against the 50% increase in the unit cost of semaglutide and the 50% decrease in the unit cost of liraglutide, as well as the changes in probabilities by the corresponding 95% confidence intervals across the model. CONCLUSIONS: This cost-effectiveness analysis suggests that employing once-weekly 2.4 mg semaglutide emerges as a remarkably cost-effective option when contrasted with once-daily 3.0 mg liraglutide in patients with overweight and obesity when added to physical activity and diet control.

Pharmacological treatment of obesity in adults in Norway 2004-2022.

AIMS: To describe trends in the use of anti-obesity drugs in Norway during the period 2004-2022. MATERIALS AND METHODS: We assessed the annual utilization of any available drug indicated for obesity recorded in the nationwide Norwegian Prescribed Drug Register for adults (age 18-79 years) from 1 January 2004 to 31 December 2022. Prevalence was stratified by sex and age group (18-29 years and 10-year age groups thereafter). Additional analyses were performed in individuals initiating treatment with an anti-obesity drug and on the cost of the anti-obesity drugs since 2017. RESULTS: The prevalence of anti-obesity drug use decreased from 2009, when sibutramine and rimonabant were withdrawn from the market, and increased again after the approval of bupropion-naltrexone in 2017 and liraglutide in 2018. The use of the peripheral-acting anti-obesity drug orlistat decreased from 2004. In 2022, 1.04% of the adult Norwegian population (72.8% women) filled at least one prescription of bupropion-naltrexone, 0.91% used liraglutide (Saxenda; 74.2% women), and semaglutide without reimbursement was used by 0.68% (76.7% women). The prevalence increased with age, peaking in the age group 50 to 59 years, and decreased in older age groups. From 2017 to 2022, 2.8% of the adult residents initiated treatment with an anti-obesity drug. The total sale of those drugs increased from 1.1 million euros in 2017 to 91.8 million euros in 2022. CONCLUSIONS: The use of anti-obesity drugs in Norway has increased substantially in recent years, especially among women aged 40 to 59 years. Changes in availability and reimbursement have influenced the use of these drugs in recent years.

Cost-effectiveness of weight-management pharmacotherapies in Canada: a societal perspective.

OBJECTIVES: This study aimed to assess the cost-effectiveness of weight-management pharmacotherapies approved by Canada Health, i.e., orlistat, naltrexone 32 mg/bupropion 360 mg (NB-32), liraglutide 3.0 mg and semaglutide 2.4 mg as compared to the current standard of care (SoC). METHODS: Analyses were conducted using a cohort with a mean starting age 50 years, body mass index (BMI) 37.5 kg/m2, and 27.6% having type 2 diabetes. Using treatment-specific changes in surrogate endpoints from the STEP trials (BMI, glycemic, blood pressure, lipids), besides a network meta-analysis, the occurrence of weight-related complications, costs, and quality-adjusted life-years (QALYs) were projected over lifetime. RESULTS: From a societal perspective, at a willingness-to-pay (WTP) threshold of CAD 50 000 per QALY, semaglutide 2.4 mg was the most cost-effective treatment, at an incremental cost-utility ratio (ICUR) of CAD 31 243 and CAD 29 014 per QALY gained versus the next best alternative, i.e., orlistat, and SoC, respectively. Semaglutide 2.4 mg extendedly dominated other pharmacotherapies such as NB-32 or liraglutide 3.0 mg and remained cost-effective both under a public and private payer perspective. Results were robust to sensitivity analyses varying post-treatment catch-up rates, longer treatment durations and using real-world cohort characteristics. Semaglutide 2.4 mg was the preferred intervention, with a likelihood of 70% at a WTP threshold of CAD 50 000 per QALY gained. However, when the modeled benefits of weight-loss on cancer, mortality, cardiovascular disease (CVD) or osteoarthritis surgeries were removed simultaneously, orlistat emerged as the best value for money compared with SoC, with an ICUR of CAD 35 723 per QALY gained. CONCLUSION: Semaglutide 2.4 mg was the most cost-effective treatment alternative compared with D&E or orlistat alone, and extendedly dominated other pharmacotherapies such as NB-32 or liraglutide 3.0 mg. Results were sensitive to the inclusion of the combined benefits of mortality, cancer, CVD, and knee osteoarthritis.

US health policy and prescription drug coverage of FDA-approved medications for the treatment of obesity.

OBJECTIVE: Obesity is now the most prevalent chronic disease in the United States, which amounts to an estimated $147 billion in health care spending annually. The Affordable Care Act (ACA) enacted in 2010 included provisions for private and public health insurance plans that expanded coverage for lifestyle/behavior modification and bariatric surgery for the treatment of obesity. Pharmacotherapy, however, has not been included despite their evidence-based efficacy. We set out to investigate the coverage of Food and Drug Administration-approved medications for obesity within Medicare, Medicaid and ACA-established marketplace health insurance plans. METHODS: We examined coverage for phentermine, diethylpropion, phendimetrazine, Benzphentamine, Lorcaserin, Phentermine/Topiramate (Qysmia), Liraglutide (Saxenda) and Buproprion/Naltrexone (Contrave) among Medicare, Medicaid and marketplace insurance plans in 34 states. RESULTS: Among 136 marketplace health insurance plans, 11% had some coverage for the specified drugs in only nine states. Medicare policy strictly excludes drug therapy for obesity. Only seven state Medicaid programs have drug coverage. CONCLUSIONS: Obesity requires an integrated approach to combat its public health threat. Broader coverage of pharmacotherapy can make a significant contribution to fighting this complex and chronic disease.

Past, present and future of pharmacotherapy for obesity. / Pasado, presente y futuro de la farmacoterapia para la obesidad.

Conventional treatment for obesity with diet, exercise and bariatric surgery has limitations; thus, it is necessary to have pharmacological tools. In the past, different drugs were marketed that were withdrawn due to safety problems. There are currently 3 drugs approved by the European Medicines Agency (EMA) and the Food and Drug Administration (FDA) for obesity therapy (orlistat, combination of bupropion and delayed-release naltrexone and liraglutide) and two more only authorized by FDA (lorcaserin and the combination of phentermine and extended release topiramate). It is recommended to use as a second therapeutic line and its choice should be individualized taking into account multiple aspects such as expected weight loss, route of administration, safety profile and cost. Currently there are several drugs under development that act on different therapeutic targets.

Estimated Costs of Clinical and Surgical Treatment of Severe Obesity in the Brazilian Public Health System.

BACKGROUND: Obesity is a major global epidemic and a burden to society and health systems. This study aimed to estimate and compare the anual costs of clinical and surgical treatment of severe obesity from the perspective of the Brazilian Public Health System. METHODS: An observational and cross-sectional study was performed in three reference centers. Data collection on health resources utilization and productivity loss was carried out through an online questionnaire. Participants were divided in clinical (waiting list for a bariatric surgery) and surgical groups (open Roux-en-Y gastric bypass), and then allocated by the time of surgery (up to 1 year; 1-2 years; 2-3 years; and >3 years). Costs of visits, medications, exams, and surgeries were obtained from government sources. Data on non-medical costs, such as transportation, special diets, and caregivers, were also colleted. Productivity loss was estimated using self-reported income. Costs in local currency (Real) were converted to international dollars (Int$ 2015). RESULTS: Two hundred and seventy-four patients, 140 in surgical group and 134 in clinical group were included. In first postoperative year, the surgical group had higher costs than clinical group (Int$6005.47 [5000.18-8262.36] versus 2148.14 [1412.2-3506.8]; p = 0.0002); however, from the second year, the costs decreased progressively. In the same way, indirect costs decreased significantly after surgery (259.08 [163.63-662.72] versus 368.17 [163.62-687.27]; p = 0.06). CONCLUSION: Total costs were higher in the surgical group in the first 2 years after surgery. However, from the third year on, the costs were lower than in the clinical group.

Cost and Health Care Utilization Implications of Bariatric Surgery Versus Intensive Lifestyle and Medical Intervention for Type 2 Diabetes.

OBJECTIVE: The aim of this study was to compare the cost and health care utilization of patients with obesity and type 2 diabetes mellitus (T2DM) randomized into either Roux-en-Y gastric bypass (RYGB) surgery or an intensive lifestyle and medical intervention (ILMI). METHODS: This analysis (N = 745) is based on 2-year follow-up of a small randomized controlled trial (RCT); adult patients with obesity and T2DM were recruited between 2011 and 2012 from Kaiser Permanente Washington. Comparisons were made for patients randomized into either RYGB (N = 15) or ILMI (N = 17). RESULTS: There were no significant cost savings for RYGB versus ILMI patients through the follow-up years. Pharmacy cost was lower for RYGB versus ILMI patients by about $900 in year 2 versus year 0; however, inpatient and emergency room costs were higher for surgery patients in follow-up years relative to year 0. Median total cost for nonrandomized patients was higher in year 0 and in year 2 compared to randomized patients. CONCLUSIONS: Bariatric surgery is not cost saving in the short term. Moreover, the costs of patients who enter into RCTs of RYGB may differ from the costs of those who do not enter RCTs, suggesting use of caution when using such data to draw inferences about the general population with obesity.

Economic evaluations of adult weight management interventions: a systematic literature review focusing on methods used for determining health impacts.

BACKGROUND: One of the challenges when undertaking economic evaluations of weight management interventions is to adequately assess future health impacts. Clinical trials commonly measure impacts using surrogate outcomes, such as reductions in body mass index, and investigators need to decide how these can best be used to predict future health effects. Since obesity is associated with an increased risk of numerous chronic diseases occurring at different future time points, modelling is needed for predictions. OBJECTIVE: To assess the methods used in economic evaluations to determine health impacts of weight management interventions and to investigate whether differences in methods affect the cost-effectiveness estimates. METHODS: Eight databases were systematically searched. Included studies were categorized according to a decision analytic approach and effect measures incorporated. RESULTS: A total of 44 articles were included; 21 evaluated behavioural interventions, 12 evaluated surgical procedures and 11 evaluated pharmacological compounds. Of the 27 papers that estimated future impacts, eleven used Markov modelling, seven used a decision tree, five used a mathematical application, two used patient-level simulation and the modelling method was unclear in two papers. The most common types of effects included were co-morbidity treatment costs, heath-related quality of life due to weight loss and gain in survival. Only 12 of the studies included heath-related quality of life gains due to reduced co-morbidities and only one study included productivity gains. Despite consensus that trial-based analysis on its own is inadequate in guiding resource allocation decisions, it was used in 39% of the studies. Several of the modelling papers used model structures not suitable for chronic diseases with changing health risks. Three studies concluded that the intervention dominated standard care; meaning that it generated more quality-adjusted life-years (QALYs) for less cost. The incremental costs per QALY gained varied from $US235 to $US56,836 in the remaining studies using this outcome measure. An implicit hypothesis of the review was that studies including long-term health effects would illustrate greater cost effectiveness compared with trial-based studies. This hypothesis is partly confirmed with three studies arriving at dominating results, as these reach their conclusion from modelling future co-morbidity treatment cost savings. However, for the remaining studies there is little indication that decision-analytic modelling disparities explain the differences. CONCLUSIONS: This is the first literature review comparing methods used in economic evaluations of weight management interventions, and it is the first time that observed differences in study results are addressed with a view to methodological explanations. We conclude that many studies have methodological deficiencies and we urge analysts to follow recommended practices and use models capable of depicting long-term health consequences.

Marine by-product phospholipids as booster of medicinal compounds.

Marine phospholipids are defined as phospholipids containing docosahexaenoic acid (DHA) or eicosapentaenoic acid that would be more effective than fish oil, which is mostly composed of triacylglycerol, in exerting health benefits. Marine phospholipids would boost the effect of both the health-beneficial hydrophilic and the hydrophobic compounds such as cell differentiators, anticancer compounds, and antiobesity compounds. When marine phospholipids are served as liposomal drinks, they would be more effective than adding into solid foods or feeds. As long as the liposome bilayer is basically composed of marine phospholipids, they would promote the encapsulated functional compounds. And this is the principal advantage of choosing marine phospholipids as liposomal membrane. Bioconversion of marine phospholipid would also be advantageous in delivering DHA into the desired tissue. For example, lysophosphatidylserine obtained through phospholipase D-mediated transphosphatidylation and phospholipase A1 or sn-1 positional specific lipase-mediated partial hydrolysis seemed to be the most effective chemical form in delivering DHA into brain.

What is the clinical effectiveness and cost-effectiveness of using drugs in treating obese patients in primary care? A systematic review.

BACKGROUND: Obesity [defined as a body mass index (BMI) ≥ 30 kg/m(2)] represents a considerable public health problem and is associated with a significant range of comorbidities and an increased mortality risk. The primary aim of the management of obesity is to achieve weight reduction in the interests of health. For obese patients who cannot achieve or maintain a healthy weight by non-pharmacological means, drug therapy is recommended in combination with non-pharmacological interventions such as dietary modifications and exercise. OBJECTIVE: To evaluate the clinical effectiveness and cost-effectiveness of three pharmacological interventions in obese patients. DATA SOURCES: Clinical effectiveness data used in the meta-analysis were sourced from articles identified in a systematic review of the literature. Data used to inform transitions to obesity-related comorbidities were derived from the General Practice Research Database (GPRD). The results of the meta-analysis and GPRD analyses informed the economic model supplemented by data from the Health Survey for England and other UK-specific data sourced from the literature. REVIEW METHODS: A systematic literature review was conducted of the clinical effectiveness and cost-effectiveness of orlistat, sibutramine and rimonabant within their licensed indications for the treatment of obese patients. Electronic bibliographic databases including MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, The Cochrane Library databases and Cumulative Index to Nursing and Allied Health Literature (CINAHL) were searched in January 2009, and the reference lists of relevant articles were checked. Studies were included if they compared orlistat, sibutramine or rimonabant with lifestyle and/or exercise advice (standard care), placebo or metformin. RESULTS: Overall, 94 studies involving 24,808 individuals were included in the clinical meta-analysis. Eighty-three trials included data on weight change, 41 included data on BMI change and 45 and 36 studies reported on 5% and 10% body weight loss, respectively. Overall, the results show that the active drug interventions are all effective at reducing weight and BMI compared with placebo. In the case of sibutramine, the higher dose (15 mg) resulted in a greater reduction than the lower dose (10 mg). Generally, the data quality of the trials included was low with poor reporting of standard errors and standard deviations. Results from the BMI risk models derived from the GPRD showed consistent increases in risk with increasing BMI. Adjustments for key confounders, such as age, sex and smoking status, were found to be statistically significant at the 5% level, in all risk models. Applying linear models to estimate BMI trajectories, for the diabetic cohort, an average increase in BMI of 0.040 per year for both men and women was observed. The non-diabetic cohort model showed an increase in BMI of 0.175 per year for women and 0.145 per year for men. The results of the cost-effectiveness analyses suggest that sibutramine 15 mg dominates the other three active interventions and the net benefit analyses show that sibutramine 15 mg is the most cost-effective alternative for thresholds > £2000 per quality-adjusted life-year (QALY). However, both sibutramine and rimonabant have been withdrawn because of safety concerns relating to potential treatment-induced fatal adverse events. If the proportion of patients who experienced a fatal adverse event was > 1.8% (1.5%, 1.0%) for sibutramine 15 mg (sibutramine 10 mg, rimonabant) the treatment would not be considered cost-effective when using a threshold of £20,000 per QALY. LIMITATIONS: The clinical review did not include all possible lifestyle comparators, with the inclusion limited to only those trials included one of the active drug interventions. We also excluded all studies not reported in English. Although the clinical review included data from 94 studies, the quality of data was generally low, particularly in terms of the reporting of standard deviation. There was also inconsistency between the results of the mixed-treatment comparison (MTC) and the pair-wise analyses. CONCLUSION: The MTC of anti-obesity treatments shows that all the active treatments are effective at reducing weight and BMI. The economic results show that, compared with placebo, the treatments are all cost-effective when using a threshold of £20,000 per QALY, and, within the limitations of the data available, sibutramine 15 mg dominates the other three interventions. This work has highlighted many areas of methodological research that could be explored, including assessing inconsistencies within a network to determine differences between the results of pair-wise and MTC analyses; the use of meta-regression methods to look for effect modifiers; exploring the effect of local publication bias; and the use of joint models to analyse the repeated measures of BMI and the time-to-event processes simultaneously. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Cost-effectiveness of pharmacotherapy to reduce obesity.

AIMS: Obesity causes a high disease burden in Australia and across the world. We aimed to analyse the cost-effectiveness of weight reduction with pharmacotherapy in Australia, and to assess its potential to reduce the disease burden due to excess body weight. METHODS: We constructed a multi-state life-table based Markov model in Excel in which body weight influences the incidence of stroke, ischemic heart disease, hypertensive heart disease, diabetes mellitus, osteoarthritis, post-menopausal breast cancer, colon cancer, endometrial cancer and kidney cancer. We use data on effectiveness identified from PubMed searches, on mortality from Australian Bureau of Statistics, on disease costs from the Australian Institute of Health and Welfare, and on drug costs from the Department of Health and Ageing. We evaluate 1-year pharmacological interventions with sibutramine and orlistat targeting obese Australian adults free of obesity-related disease. We use a lifetime horizon for costs and health outcomes and a health sector perspective for costs. Incremental Cost-Effectiveness Ratios (ICERs) below A$50 000 per Disability Adjusted Life Year (DALY) averted are considered good value for money. RESULTS: The ICERs are A$130 000/DALY (95% uncertainty interval [UI] 93 000-180 000) for sibutramine and A$230 000/DALY (170 000-340 000) for orlistat. The interventions reduce the body weight-related disease burden at the population level by 0.2% and 0.1%, respectively. Modest weight loss during the interventions, rapid post-intervention weight regain and low adherence limit the health benefits. CONCLUSIONS: Treatment with sibutramine or orlistat is not cost-effective from an Australian health sector perspective and has a negligible impact on the total body weight-related disease burden.

Pharmaceutical interventions for obesity: a public health perspective.

The prevalence of obesity, a major risk factor for many chronic diseases, has risen in most developed countries over the past several decades. The economic burden for both public and private health care systems is substantial. Although certain non-pharmaceutical interventions have been proven efficacious in specific populations, the lack of scalability has caused many of these programmes to fail in sustainably decreasing the percent of patients who are overweight or obese. The benefits of other interventions, such as pharmaceutical agents, medical devices and surgery, should therefore be carefully considered: this article focuses on the first of these strategies. Various pharmaceutical products have been plagued with safety concerns or patient non-adherence because of unpleasant side effects. Therefore, the need for additional antiobesity drugs that are both safe and effective is considerable. This article discusses the regulatory landscape for the development of new antiobesity compounds in the United States and Europe and considers the ramifications of greater or lesser regulatory burdens.

Use and costs of bariatric surgery and prescription weight-loss medications.

The extent of use of bariatric surgery and weight-loss medications is unknown. Using the Nationwide Inpatient Sample, we estimate that the number of bariatric surgeries grew 400 percent between 1998 and 2002; such surgeries were performed on 0.6 percent of the 11.5 million adults clinically eligible in 2002. Hospital costs for bariatric surgery grew sixfold to $948 million in 2002. The inpatient death rate declined 64 percent. Among employers that covered weight-loss drugs in 2002, less than 2.4 percent of adults clinically eligible for these drugs used them, with average annual spending of $304 per user.

Pharmacologic options for the treatment of obesity.

Past and current drug therapies for weight loss are discussed. More than 50% of Americans can be categorized as overweight or obese. Obesity is associated with increased mortality and with comorbidities such as hypertension, hyperglycemia, dyslipidemia, coronary artery disease, and certain cancers. According to guidelines for identification, evaluation, and treatment of obesity, patients with a body mass index (BMI) of > or = 30 kg/m2 should attempt to lose weight. Patients with a BMI of > or = 25 kg/m2 plus two or more risk factors or patients with an excessive waist circumference plus two or more risk factors should also attempt to lose weight. The initial goal is a 10% weight reduction in six months achieved through lifestyle changes. If lifestyle changes alone are not effective, then drug therapy may be indicated. Pharmacotherapeutic options for obesity have decreased over the past few years. Fenfluramine, dexfenfluramine, and phenylpropanolamine have been withdrawn because of severe adverse effects, leaving only sympathomimetics, sibutramine, and orlistat as anorectics with FDA-approved labeling. Phentermine has been shown to cause a 5-15% weight loss if given daily or intermittently. Compared with sibutramine and orlistat, phentermine is cheaper, and specific formulations allow once-daily administration. However, phentermine is indicated only for short-term treatment, and tolerance often develops. Common adverse effects associated with phentermine are dry mouth, insomnia, increased blood pressure, and constipation. Sibutramine increases norepinephrine and serotonin levels in the CNS and should not be taken with many antidepressants because of the risk of increased norepinephrine and serotonin levels. Its use is also contraindicated in patients with cardiovascular disease. Orlistat is not systemically absorbed; therefore, it does not cause the systemic adverse effects or drug interactions of phentermine and sibutramine. Orlistat has a cholesterol-lowering effect not seen with other diet medications. However, the three-times-daily administration and frequent gastrointestinal effects limit its use. Sibutramine, phentermine, and orlistat have both positive and negative properties. Choosing among the medications will depend on concurrent disease states and medications, ease of administration, and cost.