Pharmacotherapy For Obesity Research Articles

Pharmacological Treatment of Obesity in Older Adults.

Obesity is a complex health issue with growing prevalence worldwide. It is also becoming more prevalent in the population of older adults (i.e., 65 years of age and older), affecting frequency and severity as well as other comorbidities, quality of life and consequently, life expectancy. In this article we review currently available data on pharmacotherapy of obesity in the population of older adults and its role in obesity management. Even though there is growing evidence, in particular in the general population, of favourable efficacy and safety profiles of glucagon-like peptide-1 (GLP-1) receptor agonists liraglutide and semaglutide, and recently dual GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) agonist tirzepatide, concise guidelines for older adults are not available to this day. We further discuss specific approaches to frequently represented phenotype of obesity in older adults, in particular sarcopenic obesity and rationale when to treat and how. In older adults with obesity there is a need for more drug trials focusing not only on weight loss, but also on geriatric endpoints including muscle mass preservation, bone quality and favourable fat distribution changes to get enough data for evidence-based recommendation on obesity treatment in this growing sub-population.

Obesity Management in Youth with Duchenne Muscular Dystrophy: A Review of Metformin and Alternative Pharmacotherapies.

Background: Individuals with Duchenne muscular dystrophy (DMD) have increased risk of obesity from prolonged glucocorticoid use and progressive muscle weakness. Over 50% have obesity by the teenage years. Objectives: The current study examines literature on obesity management in DMD and describes how obesity pharmacotherapy can be used in this high-risk cohort. Methods: This review was conducted in adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews checklist. A Pubmed Database search was conducted from January 2000 to May 2024. Included terms were DMD and topiramate, phentermine, metformin, glucagon-like peptide-1 receptor agonist, semaglutide, and liraglutide. Eligible studies were cataloged to examine obesity pharmacotherapy, side effect profiles, and clinical outcomes. Results: Twenty studies met inclusion criteria, 18 on metformin. Reviewed studies varied in duration from 4 to 24 weeks, ages 6.5-44 years old, with 112 participants total (range: 1-30 participants). Included studies were: eight animal studies, six clinical trials, four reviews, one cohort study, and one case report. Primary outcomes varied among studies: muscular degeneration and function (15 articles), cardiac function (2 articles), weight loss (2 articles), and general endocrine care (1 article). Conclusions: Adjunct obesity pharmacotherapy use in youth with DMD is promising but needs to be confirmed. Large gaps include appropriate agent selection, side effect monitoring, and dose escalation. The overall quality of pediatric-specific evidence for the use of obesity pharmacotherapy in youth with DMD is low. Future research is needed to investigate how to safely utilize these agents.

Pediatric Obesity Pharmacotherapy: State of the Science, Research Gaps, and Opportunities.

Pediatric obesity is a major public health problem, affecting nearly 20% of children and adolescents living in the United States. In 2023, the American Academy of Pediatrics released its first clinical practice guideline for the evaluation and management of child and adolescent obesity and recommended integrating health behavior and lifestyle interventions with pharmacological treatment when medically indicated. However, there is a limited evidence base to guide antiobesity medication treatment decisions in clinical practice and limited data on long-term safety during this critical period of growth and development in youth. Thus, in November of 2023, the National Institute of Diabetes and Digestive and Kidney Diseases sponsored a workshop to identify knowledge gaps and opportunities for research on the use of pharmacotherapy for obesity in children and adolescents. Leading scientific and clinical experts in obesity pathophysiology and treatment, pharmacotherapy, clinical trial design, and health equity and disparities, among others, identified gaps in clinical trial design, guidance for clinical use of medications in children and adolescents, additional treatment outcomes beyond body fat or weight, and improvement in care delivery. Adolescent patients and caregivers with lived experience of obesity and weight management were also invited to participate in a panel discussion, providing personal perspectives on living with obesity, clinical care considerations, and research needs. This article summarizes the workshop proceedings on the state of the science and identifies gaps and opportunities for future research to inform optimal and equitable medical management of children and adolescents with obesity.

8040 Precision-Engineered Activin and GDF Ligand Trap HS235: A Novel Lean Mass-Preserving Treatment for Obesity

Abstract Disclosure: G. Schang: Employee; Self; 35Pharma. M. De Molliens: Employee; Self; 35Pharma. E. Brule: Employee; Self; 35Pharma. C. Chauvet: Employee; Self; 35Pharma. J. Denis: Employee; Self; 35Pharma. A. Sours: Employee; Self; 35Pharma. V. Ganesh: Employee; Self; 35Pharma. G. Tremblay: Employee; Self; 35Pharma. J. Schoelermann: Employee; Self; 35Pharma. M. O'Connor: Employee; Self; 35Pharma. Introduction: Novel anti-obesity medications including incretin mimetics have revolutionized the pharmacotherapy of obesity and type 2 diabetes, leading to unprecedented weight loss and clinically meaningful improvement of glucose metabolism and cardiometabolic health. However, incretins reduce body mass in a non-selective manner; both fat mass and lean mass are lost with incretin treatment. In obese patients treated with incretins, undesirable loss of lean body mass (LBM) can account for up to 40% of overall weight loss. Loss of LBM negatively impacts resting metabolic rate, leading to a weight loss plateau and often unsustainable results. Furthermore, individuals with sarcopenia, characterized by low muscle mass and strength, are at greater risk for heart failure. The preservation, or even increase, of LBM is therefore a desirable treatment goal for obesity pharmacotherapy and overall cardiometabolic health. Activins and growth differentiation factors (GDFs), which are members of the TGF-beta superfamily, are validated targets controlling body composition and metabolism. Specifically, blockade of activins and GDFs has anabolic effects in metabolically active tissues such as skeletal muscle and brown adipose tissue, while reducing white adipose tissue mass. Therefore, specific and selective blockade of activins and GDFs represents a novel anti-obesity treatment strategy which can act orthogonally to current anti-obesity medications. HS235 is an activin receptor ectodomain-based (ActR) Fc-fusion protein that has been rationally designed to attain optimal inhibition of ligands controlling body composition in obesity. Methods: A structure-assisted rational molecular engineering approach coupled with cell-based potency screening was employed to design HS235. To validate the anti-obesogenic potential of HS235, diet-induced obese (DIO) mice were injected with HS235, an incretin mimetic, or a combination of both. Fat mass, LBM, muscle weights, and biomarker readouts were assessed at the end of study. Results: In cell-based assays, HS235 potently and selectively neutralized activins and GDFs implicated in body composition. This translated to complete in vivo target engagement and pharmacodynamic response. In a DIO mouse model, both HS235 and the incretin mimetic significantly improved metabolic parameters and decreased fat mass, but only HS235 increased LBM, while incretin-based treatment led to LBM loss. Importantly, the addition of HS235 to the incretin mimetic lead to a synergistic fat mass loss and prevented loss of LBM. Conclusion: Potent and selective inhibition of activins and GDFs by HS235 represents a novel LBM preserving weight loss strategy orthogonal to incretin mimetics. Collectively, these data support the development of HS235 as a novel anti-obesity agent to complement currently approved incretin-based medications to improve quality of weight loss. Presentation: 6/3/2024

Patient, facility, and environmental factors associated with obesity treatment in US Veterans.

Identifying patient-, facility-, and environment-level factors that influence the initiation and retention of comprehensive lifestyle management interventions (CLMI) for urban and rural Veterans could improve obesity treatment and reach at Veterans Affairs (VA) facilities. This study identified factors at these various levels that predicted treatment engagement, retention, and weight management among urban and rural Veterans. A retrospective cohort study of 631,325 Veterans was designed using VA databases to identify Veterans with class II and III obesity during 2015-2017. Primary outcomes were initiation of CLMI, bariatric surgery, or obesity pharmacotherapy within 1year of index date. Secondary outcomes included treatment retention and successful weight loss. Generalized linear mixed models were used to evaluate the relationships between factors and obesity-related outcomes, with rurality differences assessed through interaction terms. Patient characteristics associated with increased odds of initiating CLMI included female sex (p<0.001), black race (p<0.001), sleep apnea (p<0.001), mood disorder (p<0.001), and use of medications associated with weight loss (p<0.001) or weight gain (p<0.001). Facility use of telehealth was associated with greater odds of CLMI initiation in urban Veterans (p<0.001) but lower retention in both populations (p=0.003). Routine consideration of pharmacotherapy was associated with higher CLMI initiation. Environmental characteristics associated with increased odds of CLMI initiation included percent of population foreign born (OR=1.03 per 10% increase; p<0.001), percent black (p<0.001), and high walkability index (p<0.001). The relationship between total population and CLMI initiation differed by rurality, as greater population was associated with lower odds of CLMI initiation in urban areas (OR: 0.99 per 1000 population; p<0.001), but higher odds in rural areas (OR:1.01, p=0.01). Veterans in the south were less likely to initiate CLMI and had lower retention (p<0.001). Treatment and retention of CLMI among Veterans remain low, highlighting areas for improvement to expand its reach both urban and rural Veterans.

Tackling Cravings in Medical Weight Management: An Update on Pathophysiology and an Integrated Approach to Treatment

Background/Objectives: Food cravings involve a strong drive to consume palatable foods irrespective of nutritional status. Importantly, cravings contribute substantially to the obesity epidemic. Managing hunger alone is insufficient for weight management as this relates only to homeostatic eating and does not address the complex aetiology of hedonic eating and its crucial role in food cravings. Medical weight management clinics and anti-obesity medication trials do not routinely identify and address food cravings. Methods: We conducted a narrative review of the literature consisting of 115 peer-reviewed articles (original articles and reviews). We included articles focused on food craving pathophysiology, assessment, and management strategies providing contrasts against the current medical model of weight management seen in obesity pharmacotherapy trials as well as the current standard of practise. Results: We outline the neurohormonal and psychological drivers of cravings, which lead to a spectrum of eating behaviours, from comfort food eating to binge eating disorders. We provide an overview of ways of identification and measurement options, including their strengths and weaknesses, and an overview of management strategies and their cravings control efficacy, spanning lifestyle modifications like nutrition and sleep, psychological therapies (i.e., cognitive behavioural therapy [CBT], acceptance-based therapies such as mindfulness) and, last but not least, medications that not only are approved for weight reduction but reduce cravings. Finally, based on these findings, we provide a proposed integrated and iterative model that is able to evolve and adapt to the individual over time in tackling cravings for long-term weight loss maintenance. Conclusions: The findings emphasise the importance of cravings management and provide a synthesis on how cravings can be identified in a medical weight management setting, which can be practically implemented in an integrated iterative model spanning anti-obesity medications that have craving control data to evidence-based lifestyle and psychological interventions.

Skeletal muscle loss and sarcopenia in obesity pharmacotherapy

Skeletal muscle loss and sarcopenia in obesity pharmacotherapy

Incretin hormone agonists: Current and emerging pharmacotherapy for obesity management.

Obesity continues to be a significant global health challenge, affecting over 800 million individuals worldwide. Traditional management strategies, including dietary, exercise, and behavioral interventions, often result in insufficient and unsustainable weight loss. Lifestyle modification remains the cornerstone of obesity management, providing the foundation for other strategies. While options such as bariatric surgery remain an effective intervention for severe obesity, it is associated with its own set of risks and is typically reserved for patients who have not achieved the desired results with pharmacotherapy and lifestyle interventions. Incretin hormone agonists represent a significant advancement in the pharmacotherapy of obesity, offering substantial weight reduction and cardiometabolic benefits. Agents like liraglutide, semaglutide, and tirzepatide supported by key clinical trials such as Satiety and Clinical Adipose Liraglutide Evidence (SCALE), Semaglutide Treatment Effect in People with Obesity (STEP) program trials, and Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1) have demonstrated remarkable efficacy in promoting weight loss and improving metabolic outcomes. Additionally, novel therapies, including dual and triple incretin agonists, are under investigation and hold the potential for further advancements in obesity treatment. These novel therapies can be categorized by their mechanisms of action and route of administration into oral glucagon-like peptide-1 (GLP-1) receptor agonists, triple agonists (targeting GLP-1, glucose-dependent insulinotropic polypeptide [GIP], and glucagon receptors), and glucagon receptor-GLP-1 receptor co-agonists. Other innovative approaches include oral GIP-GLP-1 receptor co-agonists, and the combination of long-acting amylin receptor agonists with GLP-1 receptor agonists. The ongoing development of incretin-based therapies and the expanding availability of currently available agents are expected to enhance clinical outcomes further and reduce the burden of obesity-related health complications. This review aims to discuss the mechanisms and efficacy of current and emerging incretin hormone agonists for obesity management.

Pharmacotherapy in obesity

Pharmacotherapy in obesity

Off-label pharmacotherapy of obesity: a systematic review

Off-label pharmacotherapy of obesity: a systematic review

Precision medicine for obesity: current evidence and insights for personalization of obesity pharmacotherapy.

Obesity is a chronic and complex disease associated with increased morbidity, mortality, and financial burden. It is expected that by 2030 one of two people in the United States will have obesity. The backbone for obesity management continues to be lifestyle interventions, consisting of calorie deficit diets and increased physical activity levels, however, these interventions are often insufficient to achieve sufficient and maintained weight loss. As a result, multiple patients require additional interventions such as antiobesity medications or bariatric interventions in order to achieve clinically significant weight loss and improvement or resolution of obesity-associated comorbidities. Despite the recent advances in the field of obesity pharmacotherapy that have resulted in never-before-seen weight loss outcomes, comorbidity improvement, and even reduction in cardiovascular mortality, there is still a significant interindividual variability in terms of response to antiobesity medications, with a subset of patients not achieving a clinically significant weight loss. Currently, the trial-and-error paradigm for the selection of antiobesity medications results in increased costs and risks for developing side effects, while also reduces engagement in weight management programs for patients with obesity. The implementation of a precision medicine framework to the selection of antiobesity medications might help reduce heterogeneity and optimize weight loss outcomes by identifying unique subsets of patients, or phenotypes, that have a better response to a specific intervention. The detailed study of energy balance regulation holds promise, as actionable behavioral and physiologic traits could help guide antiobesity medication selection based on previous mechanistic studies. Moreover, the rapid advances in genotyping, multi-omics, and big data analysis might hold the key to discover additional signatures or phenotypes that might respond better to a certain intervention and might permit the widespread adoption of a precision medicine approach for obesity management.

Therapeutic Advances in Obesity: How Real-World Evidence Impacts Affordability Beyond Standard of Care.

Obesity is currently considered a global epidemic, with rising prevalence worldwide and rather pessimistic projections. Based on its close interconnection with various co-morbidities, such as diabetes mellitus and cardiovascular disease, obesity is associated with significant increases in morbidity and mortality, while it also poses a substantial economic burden for national healthcare systems. Apparently, the majority of individuals classified as obese do not achieve adequate weight loss with the adoption of a healthy lifestyle intervention, including dietary modification and physical activity. Fortunately, during the last decade, a significant progress in pharmacotherapy of obesity has been observed, with the introduction of agents that have gained approval from regulatory authorities, namely semaglutide, liraglutide and tirzepatide, due to their impressive results in body weight reduction, alongside their beneficial, pleiotropic effects. The aim of the present review article is to discuss on evidence retrieved from real-world studies regarding the efficacy of those agents in obesity treatment, with emphasis on cost-effectiveness data, towards an effort to tackle efficiently the progression of obesity epidemic.

Possibilities of using glucagon-like peptide-1 agonists and incretin multi-agonists in pharmacotherapy of obesity and metabolic syndrome

Obesity is a predisposing factor in the development of a number of non-communicable diseases. The current Russian clinical guidelines for the treatment of obesity in adults include the following drugs: orlistat, sibutramine, sibutramine+metformin, liraglutide. Currently, hypoglycemic agents such as glucagon-like peptide-1 (GLP-1) agonists and incretin multi-agonists are being actively studied in the treatment of obesity, especially in comorbid patients. Long-acting GLP-1 agonists and incretin multi-agonists have demonstrated clinically significant efficacy in reducing body weight among hypoglycemic drugs in a number of pilot and larger studies. The data obtained regarding the effectiveness of the above drugs indicate the need to expand existing clinical recommendations for the treatment of patients with obesity and introduce into clinical practice alternative drugs, the use of which is quite safe and well tolerated by patients.

Pharmacotherapy of obesity and metabolic syndrome. Focus on sodium-glucose cotransporter type 2 inhibitors

The current Russian clinical guidelines for the treatment of obesity in adults include the following drugs: orlistat, sibutramine, sibutramine + metformin, liraglutide. However, in many cases the use of the first two drugs is limited or contraindicated. In a significant number of clinical cases, drug treatment of obesity, especially in comorbid patients, requires consideration of other groups of drugs that have a positive effect on concomitant pathology, such as, for instance, new classes of hypoglycemic drugs — sodium-glucose cotransporter type 2 (SGLT2) inhibitors. The hypoglycemic agents presented in this article contributed to varying degrees of weight loss. The data obtained regarding the effectiveness of the above drugs indicate the need to expand existing clinical recommendations for the treatment of patients with obesity and introduce into clinical practice alternative drugs, the use of which is quite safe and well tolerated by patients.

Current options in obesity pharmacotherapy for children and adolescents

Obesity is pervasive from infancy to adulthood and presents a major challenge to healthcare systems worldwide. In children and adolescents, the prevalence of overweight and obesity continues to increase, especially in classes II and III, and in younger toddlers and preschool-aged children. Childhood obesity may be associated with comorbidities in all organ systems and increased cardiovascular risk, as it tracks into adolescent and adult obesity. Although intensive health and behavior lifestyle treatments form the foundation of obesity treatment, there are limitations in the extent and maintenance of weight loss with lifestyle modifications alone. The offering of obesity pharmacotherapy in adjunct to intensive lifestyle treatment in children aged &gt; 12 years may improve outcomes in pediatric obesity. In this review, we discuss currently approved medications for childhood and adolescent obesity, focusing on orlistat, phentermine monotherapy, glucagon-like peptide-1 receptor agonists (liraglutide and semaglutide injections), and phentermine/topiramate combination.

Metabolic alliance: pharmacotherapy and exercise management of obesity.

Metabolic alliance: pharmacotherapy and exercise management of obesity.

A Review on Pharmacological and Non-Pharmacological Therapy for the treatment of Obesity with Cardiovascular Diseases

One of the biggest issues facing the globe today is obesity. It primarily correlates with heart disease. Obesity can raise the risk of cardiovascular illness or muscle-related problems. Numerous fat tissues secrete bio-active cytokines, and these mediators affectglucose resistance, diabetes mellitus, hypertension, atherosclerosis, and heart attacks in addition to body weight homeostasis. Currently, there are three treatment options for obesity: pharmacological therapy, bariatric surgery, and lifestyle modification or non-pharmacotherapy (such as physical therapy, cognitive behavioral therapy, and healthy food planning). The market with the quickest rate of growth is pharmacotherapy. phentermine plus topiramate, Belviq, semaglutide, and naltrexone plus bupropion are among the medications used in pharmacological therapy. The Federal Drug Administration of the United States has authorized the first two drugs based on clinical studies that showed improvements in lipid profile, glucose resistance, and overweight. In this review, we will address the effectiveness of previous pharmacotherapy for obesity, with an emphasis on new therapeutic agents that enhance patient safety.

Genetics, pharmacotherapy, and dietary interventions in childhood obesity.

Childhood obesity has emerged as a major global health issue, contributing to the increased prevalence of chronic conditions and adversely affecting the quality of life and future prospects of affected individuals, thereby presenting a substantial societal challenge. This complex condition, influenced by the interplay of genetic predispositions and environmental factors, is characterized by excessive energy intake due to uncontrolled appetite regulation and a Westernized diet. Managing obesity in childhood requires specific considerations compared with adulthood, given the vulnerability of the critical juvenile-adolescent period to toxicity and developmental defects. Consequently, common treatment options for adult obesity may not directly apply to younger populations. Therefore, research on childhood obesity has focused on genetic defects in regulating energy intake, alongside pharmacotherapy and dietary interventions as management approaches, with an emphasis on safety concerns. This review aims to summarize canonical knowledge and recent findings on genetic factors contributing to childhood obesity. Additionally, it assesses the efficacy and safety of existing pharmacotherapies and dietary interventions and suggests future research directions. By providing a comprehensive understanding of the complex dynamics of childhood obesity, this review aims to offer insights into more targeted and effective strategies for addressing this condition, including personalized healthcare solutions.

Genetic or pharmacological GHSR blockade has sexually dimorphic effects in rodents on a high-fat diet

The stomach-derived hormone ghrelin regulates essential physiological functions. The ghrelin receptor (GHSR) has ligand-independent actions; therefore, GHSR gene deletion may be a reasonable approach to investigate the role of this system in feeding behaviors and diet-induced obesity (DIO). Here, we investigate the effects of a long-term (12-month) high-fat (HFD) versus regular diet on obesity-related measures in global GHSR-KO and wild-type (WT) Wistar male and female rats. Our main findings are that the GHSR gene deletion protects against DIO and decreases food intake during HFD in male but not in female rats. GHSR gene deletion increases thermogenesis and brain glucose uptake in male rats and modifies the effects of HFD on brain glucose metabolism in a sex-specific manner, as assessed with small animal positron emission tomography. We use RNA-sequencing to show that GHSR-KO rats have upregulated expression of genes responsible for fat oxidation in brown adipose tissue. Central administration of a novel GHSR inverse agonist, PF-5190457, attenuates ghrelin-induced food intake, but only in male, not in female mice. HFD-induced binge-like eating is reduced by inverse agonism in both sexes. Our results support GHSR as a promising target for new pharmacotherapies for obesity.

The effect of obesity pharmacotherapy on body composition, including muscle mass.

Obesity pharmacotherapy represents a promising approach to treating obesity and may provide benefits beyond weight loss alone. Maintaining or even increasing muscle mass during weight loss is important to overall health, metabolic function and weight loss maintenance. Drugs such as liraglutide, semaglutide, tirzepatide, and naltrexone/bupropion have shown significant weight loss effects, and emerging evidence suggests they may also have effects on body composition, particularly a positive influence on muscle mass. However, further research is needed to fully understand the mechanism of action of these drugs and their effects on muscle mass. Clinicians should consider these factors when developing an obesity treatment plan for an individual patient.