Comprehensive assessment of the anti-obesity effects of highland barley total, insoluble, and soluble dietary fiber through multi-omics analysis.

The impact of different forms of dietary fiber (total, insoluble or soluble) derived from the same source on health remains incompletely understood. In this study, the effects of total, insoluble, and soluble dietary fiber extracted from highland barley (HDF, HIDF, and HSDF) on combating obesity were evaluated and compared. A high-fat diet (HFD) was used to induce obesity in a murine model, followed by gavage administration of HDF, HIDF, or HSDF, and a comprehensive multi-omics approach was utilized to assess and compare the effects of these dietary fibers on obesity-related parameters. The results showed that all three dietary fibers significantly reduced body weight, modified blood lipid profiles, and ameliorated tissue damage in HFD-fed mice. Additionally, 16S rRNA sequencing analysis of mice feces showed that three types of dietary fiber exerted varying degrees of impact on the composition and abundance of gut microbiota while simultaneously promoting the biosynthesis of short-chain fatty acids. Specifically, HDF supplementation remarkably enhanced the abundance of Coprococcus, while HIDF and HSDF supplementation elevated the levels of Akkermansia and Allobaculum, respectively. Transcriptomic and proteomic results suggested the PPAR signaling pathway as a central regulatory mechanism influenced by these fibers. HDF and HIDF were particularly effective in modulating biological processes related to triglyceride and fatty acid metabolism, identifying Abcc3 and Dapk1 as potential targets. Conversely, HSDF primarily affected processes related to membrane lipids, ceramides, and phospholipids metabolism, with Pck1 identified as a potential target. Collectively, HDF, HIDF, and HSDF demonstrated distinct mechanisms in exerting exceptional anti-obesity properties. These insights may inform the development of personalized dietary interventions for obesity.

Butein derivatives prevent obesity and improve insulin resistance through the induction of energy expenditure in high-fat diet-fed obese mice.

Obesity is a global public health problem and is related with fatal diseases such as cancer and cardiovascular and metabolic diseases. Medical and lifestyle-related strategies to combat obesity have their limitations. White adipose tissue (WAT) browning is a promising strategy for increasing energy expenditure in individuals with obesity. Uncoupling protein 1 (UCP1) drives WAT browning. We previously screened natural products that enable induction of Ucp1 and demonstrated that these natural products induced WAT browning and increased energy expenditure in mice with diet-induced obesity. In this study, we aimed to extensively optimise the structure of compound 1, previously shown to promote WAT browning. Compound 3 s exhibited a significantly higher ability to induce Ucp1 in white and brown adipocytes than did compound 1. A daily injection of compound 3 s at 5 mg/kg prevented weight gain by 13.6 % in high-fat diet-fed mice without any toxicological observation. In addition, compound 3 s significantly improved glucose homeostasis, decreased serum triacylglycerol levels, and reduced total cholesterol and LDL cholesterol levels, without altering dietary intake or physical activity. Pharmaceutical properties such as solubility, lipophilicity, and membrane permeability as well as metabolic stability, half-life (T1/2), and blood exposure ratio of i.p to i.v were significantly improved in compound 3 s when compared with those in compound 1. Regarding the mode of action of WAT browning, the induction of Ucp1 and Prdm4 by compounds 1 and 3 s was dependent on Akt1 in mouse embryonic fibroblasts. Therefore, this study suggests the potential of compound 3 s as a therapeutic agent for individuals with obesity and related metabolic diseases, which acts through the induction of WAT browning as well as brown adipose tissue activation.

Semaglutide for management of obesity in adolescents: efficacy, safety, and considerations for clinical practice.

PURPOSE OF REVIEW: The purpose of this review is to describe the existing limited data related to the use of semaglutide in adolescents with obesity, supplementing with findings from adult studies of semaglutide use. RECENT FINDINGS: Semaglutide, as a once weekly subcutaneous injection for weight management, effectively reduces body mass index (BMI) while improving hyperglycemia, elevated alanine aminotransferase levels, hyperlipidemia, and quality of life in youth with obesity. As of this review, only one large randomized clinical trial of semaglutide in youth has been completed, with a follow-up duration of 68 weeks. Thus, long-term data on the safety in adolescents is limited, particularly regarding the risks of cholelithiasis, pancreatitis, suicidal ideation, and disordered eating. Due to the cost of semaglutide, particularly in the United States, limited cost effectiveness analyses have demonstrated unfavorable incremental cost-effectiveness ratios for semaglutide relative to phentermine-topiramate as an alternative antiobesity medication in adolescents. SUMMARY: Semaglutide represents an important advance in the pediatric obesity management, with clear short-term reductions in BMI and improvement in metabolic parameters. However, its long-term safety and efficacy for youth with obesity remain to be demonstrated. Additional research is needed to assess trends in utilization and adherence to minimize the risk of worsening socioeconomic disparities in pediatric obesity.

The association between weight loss medications and cardiovascular complications.

OBJECTIVE: Obesity and its cardiovascular complications are major causes of morbidity and mortality. Little is known in real-world settings about the effect of newly approved antiobesity medications (AOMs) on cardiovascular complications among patients with obesity. METHODS: This retrospective cohort study examined the association between newly approved AOM use and cardiovascular events among Medicare patients with obesity using data from 2020 to 2022. Patient age, gender, comorbidity scores, socioeconomic status, and baseline cardiovascular comorbidities were compared descriptively. Subgroup analysis compared variables by medication type. Relative risk and absolute risk of cardiovascular disease (CVD) events were estimated using Cox and Aalen regression models. RESULTS: The analysis included 5926 patients treated with semaglutide and tirzepatide, including Ozempic (5404 patients), Wegovy (375 patients), or Mounjaro (147 patients). Hypertension, type 2 diabetes, and hyperlipidemia were the most common comorbidities. For patients with AOMs, less incidence of heart failure (4.89% vs. 6.13%, p < 0.0001), atrial fibrillation (3.83% vs. 5.17%, p < 0.0001), arrhythmia (3.59% vs. 4.14%, p < 0.0153), and peripheral vascular disease (3.44% vs. 2.94%, p < 0.0395) was found versus patients without AOMs. Patients receiving AOMs showed an 8% risk reduction in any CVD. Protective effect on CVD was apparent over the first 375 days. CONCLUSIONS: Results suggest that utilization of AOMs effectively alleviates the high prevalence of CVD.

Female obesity: clinical and psychological assessment toward the best treatment.

Obesity is a heterogeneous condition which results from complex interactions among sex/gender, sociocultural, environmental, and biological factors. Obesity is more prevalent in women in most developed countries, and several clinical and psychological obesity complications show sex-specific patterns. Females differ regarding fat distribution, with males tending to store more visceral fat, which is highly correlated to increased cardiovascular risk. Although women are more likely to be diagnosed with obesity and appear more motivated to lose weight, as confirmed by their greater representation in clinical trials, males show better outcomes in terms of body weight and intra-abdominal fat loss and improvements in the metabolic risk profile. However, only a few relatively recent studies have investigated gender differences in obesity, and sex/gender is rarely considered in the assessment and management of the disease. This review summarizes the evidence of gender differences in obesity prevalence, contributing factors, clinical complications, and psychological challenges. In addition, we explored gender differences in response to obesity treatments in the specific context of new anti-obesity drugs.

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.

Medicare Should Cover Weight Loss Drugs as Long as the Prices are Affordable.

Glucagon-like peptide-1 receptor agonists are effective for treating obesity, but the high cost of these medications endangers the financial viability of our health care system. To ensure that these drugs are available to Medicare beneficiaries, pharmaceutical manufacturers must lower their prices.

Economic Evaluations of Anti-obesity Interventions in Obese Adults: An Umbrella Review.

This umbrella review amalgamates the outcomes of economic evaluations pertaining to bariatric surgeries, pharmacotherapy, and gastric balloon for adult obesity treatment. Six databases were systematically searched. The inclusion criteria were established following the Patient/population Intervention Comparison and Outcomes (PICO) statement. Fifteen reviews met all the inclusion criteria. Eight studies focused on surgical interventions, four on pharmacotherapy, and three on both interventions. No systematic review of the economic evaluation of gastric balloons was identified. The majority of reviews advocated bariatric surgery as a cost-effective approach; however, there was discordance in the interpretation of pharmacological cost-effectiveness. Most of the economic evaluations were conducted from the payer and the healthcare system perspectives. We propose that future economic evaluations assessing weight loss interventions in adults adopt a societal perspective and longer-term time horizons.

State Coverage and Reimbursement of Antiobesity Medications in Medicaid.

This study examines state Medicaid coverage policies for antiobesity medications and their trends in Medicaid reimbursement from 2011 to 2022.

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.

Association of patient characteristics and insurance type with anti-obesity medications prescribing and fills.

AIM: To characterize factors associated with the receipt of anti-obesity medication (AOM) prescription and fill. MATERIALS AND METHODS: This retrospective cohort study used electronic health records from 1 January 2015 to 30 June 2023, in a large health system in Ohio and Florida. Adults with a body mass index ≥30 kg/m2 who attended ≥1 weight-management programme or had an initial AOM prescription between 1 July 2015 and 31 December 2022, were included. The main measures were a prescription for an AOM (naltrexone-bupropion, orlistat, phentermine-topiramate, liraglutide 3.0 mg and semaglutide 2.4 mg) and an AOM fill during the study follow-up. RESULTS: We identified 50 678 adults, with a mean body mass index of 38 ± 8 kg/m2 and follow-up of 4.7 ± 2.4 years. Only 8.0% of the cohort had AOM prescriptions and 4.4% had filled prescriptions. In the multivariable analyses, being a man, Black, Hispanic and other race/ethnicity (vs. White), Medicaid, traditional Medicare, Medicare Advantage, self-pay and other insurance types (vs. private insurance) and fourth quartile of the area deprivation index (vs. first quartile) were associated with lower odds of a new prescription. Hispanic ethnicity, being a man, Medicaid, traditional Medicare and Medicare Advantage insurance types, liraglutide and orlistat (vs. naltrexone-buproprion) were associated with lower odds of AOM fill, while phentermine-topiramate was associated with higher odds. Among privately insured individuals, the insurance carrier was associated with both the odds of AOM prescription and fill. CONCLUSIONS: Significant disparities exist in access to AOM both at the prescribing stage and getting the prescription filled based on patient characteristics and insurance type.

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.

Medicare Part D Coverage of Anti-obesity Medications: a Call for Forward-Looking Policy Reform.

When the Medicare Part D benefit was constructed, drugs for weight loss were explicitly excluded from coverage, as the limited effectiveness and unfavorable safety profile of medications available at the time failed to justify coverage of drugs perceived to be used for cosmetic purposes. In recent years, drugs activating the glucagon-like peptide-1 receptor (GLP-1R) pathway have proved to achieve significant reductions in body weight with a favorable safety profile. The effectiveness of GLP-1R agonists in reducing weight and improving the metabolic profile warrants the reconsideration of the historical exclusion of weight loss drugs from Part D coverage. In this perspective, we outline policy options to enable Part D coverage of GLP-1R agonists. These include legislative change through the passage of the Treat and Reduce Obesity Act and evaluation of coverage policies under the waiver authority of the Center for Medicare and Medicaid Innovation.

Pharmacoeconomic evaluation of anti-obesity drugs for chronic weight management: a systematic review of literature.

Introduction: Pharmacological therapy is recommended as a second-line alternative to reverse obesity. Currently, five anti-obesity drugs (AODs) have been approved by the U.S. Food and Drug Administration (FDA) for chronic weight management. The aim of this paper is to investigate the pharmacoeconomic evaluation of AODs through a systematic review with a special focus on methodological considerations. Methods: We searched the general and specific databases to identify the primary pharmacoeconomic evaluation of AODs. Results: A total of 18 full-text articles and three conference abstracts were included in this review. Most of the economic assessments were still about Orlistat. And the observations we could make were consistent with the previous systematic review. A few studies were on the combined therapies (i.e. PHEN/TPM ER and NB ER) compared to different comparators, which could hardly lead to a generalized summary of the cost-effectiveness. Most recently, pharmacoeconomic evidence on the newest GLP 1 RA approved for the indication of obesity or obesity with at least one comorbidity emerged gradually. Modelling-based cost-utility analysis is the major type of assessment method. In the modelling studies, a manageable number of the key health states and the state transitions were structured to capture the disease progression. In particular, the principal structure of the decision model adopted in the three studies on the newly approved drug was nearly the same, which enables more in-depth comparisons and generalizations of the findings. Conclusion: This study provided an up-to-date overview of the strengths and areas for improvement in the methodological design of the pharmacoeconomic evaluation of the licensed drugs for chronic weight management. Future modelling evaluations would benefit from a better understanding of the long-term weight loss effects of the current therapeutic options and the weight rebound process after the discontinuation of treatment. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022302648, identifier CRD42022302648.

Cost-Effectiveness of Antiobesity Drugs for Adolescents With Severe Obesity.

Importance: Although the American Academy of Pediatrics has recommended treatment with antiobesity drugs for adolescents, the cost-effectiveness of antiobesity drugs for this population is still unknown. Objective: To quantify cost-effectiveness of different antiobesity drugs available for pediatric use. Design, Setting, and Participants: This economic evaluation used a Markov microsimulation model with health states defined by obesity levels. Effectiveness was measured by quality-adjusted life-years (QALYs) and costs were calculated from third-party payer perspective, estimated in 2023 US dollars over a 10-year horizon. Data were obtained from the published literature. Intervention: Antiobesity drugs orlistat, liraglutide, semaglutide, and phentermine-topiramate vs no treatment. Metformin hydrochloride and 2 types of bariatric surgical procedures (sleeve gastrectomy and gastric bypass) were considered in sensitivity analysis. Main Outcomes and Measures: Incremental cost-effectiveness ratio. Results: Among the 4 antiobesity drugs currently approved for pediatric use, phentermine-topiramate was the most cost-effective with an incremental cost-effectiveness ratio of $93 620 per QALY relative to no treatment in this simulated cohort of 10 000 adolescents aged 12 to 17 years (mode, 15 years) with severe obesity (62% female). While semaglutide offered more QALYs than phentermine-topiramate, its higher cost resulted in an incremental cost-effectiveness ratio ($1 079 480/QALY) that exceeded the commonly used willingness-to-pay threshold of $100 000 to $150 000/QALY. Orlistat and liraglutide cost more and were less effective than phentermine-topiramate and semaglutide, respectively. Sleeve gastrectomy and gastric bypass were more effective than phentermine-topiramate but were also more costly, rendering them not cost-effective compared with phentermine-topiramate at the willingness-to-pay threshold of $100 000 to $150 000/QALY. Conclusions and Relevance: In this economic evaluation of weight loss drugs for adolescents with severe obesity, we found phentermine-topiramate to be a cost-effective treatment at a willingness-to-pay threshold of $100 000 to $150 000/QALY. Further research is needed to determine long-term drug efficacy and how long adolescents continue treatment.