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JAMA Nov 2023Obesity affects approximately 42% of US adults and is associated with increased rates of type 2 diabetes, hypertension, cardiovascular disease, sleep disorders,... (Review)
Review
IMPORTANCE
Obesity affects approximately 42% of US adults and is associated with increased rates of type 2 diabetes, hypertension, cardiovascular disease, sleep disorders, osteoarthritis, and premature death.
OBSERVATIONS
A body mass index (BMI) of 25 or greater is commonly used to define overweight, and a BMI of 30 or greater to define obesity, with lower thresholds for Asian populations (BMI ≥25-27.5), although use of BMI alone is not recommended to determine individual risk. Individuals with obesity have higher rates of incident cardiovascular disease. In men with a BMI of 30 to 39, cardiovascular event rates are 20.21 per 1000 person-years compared with 13.72 per 1000 person-years in men with a normal BMI. In women with a BMI of 30 to 39.9, cardiovascular event rates are 9.97 per 1000 person-years compared with 6.37 per 1000 person-years in women with a normal BMI. Among people with obesity, 5% to 10% weight loss improves systolic blood pressure by about 3 mm Hg for those with hypertension, and may decrease hemoglobin A1c by 0.6% to 1% for those with type 2 diabetes. Evidence-based obesity treatment includes interventions addressing 5 major categories: behavioral interventions, nutrition, physical activity, pharmacotherapy, and metabolic/bariatric procedures. Comprehensive obesity care plans combine appropriate interventions for individual patients. Multicomponent behavioral interventions, ideally consisting of at least 14 sessions in 6 months to promote lifestyle changes, including components such as weight self-monitoring, dietary and physical activity counseling, and problem solving, often produce 5% to 10% weight loss, although weight regain occurs in 25% or more of participants at 2-year follow-up. Effective nutritional approaches focus on reducing total caloric intake and dietary strategies based on patient preferences. Physical activity without calorie reduction typically causes less weight loss (2-3 kg) but is important for weight-loss maintenance. Commonly prescribed medications such as antidepressants (eg, mirtazapine, amitriptyline) and antihyperglycemics such as glyburide or insulin cause weight gain, and clinicians should review and consider alternatives. Antiobesity medications are recommended for nonpregnant patients with obesity or overweight and weight-related comorbidities in conjunction with lifestyle modifications. Six medications are currently approved by the US Food and Drug Administration for long-term use: glucagon-like peptide receptor 1 (GLP-1) agonists (semaglutide and liraglutide only), tirzepatide (a glucose-dependent insulinotropic polypeptide/GLP-1 agonist), phentermine-topiramate, naltrexone-bupropion, and orlistat. Of these, tirzepatide has the greatest effect, with mean weight loss of 21% at 72 weeks. Endoscopic procedures (ie, intragastric balloon and endoscopic sleeve gastroplasty) can attain 10% to 13% weight loss at 6 months. Weight loss from metabolic and bariatric surgeries (ie, laparoscopic sleeve gastrectomy and Roux-en-Y gastric bypass) ranges from 25% to 30% at 12 months. Maintaining long-term weight loss is difficult, and clinical guidelines support the use of long-term antiobesity medications when weight maintenance is inadequate with lifestyle interventions alone.
CONCLUSION AND RELEVANCE
Obesity affects approximately 42% of adults in the US. Behavioral interventions can attain approximately 5% to 10% weight loss, GLP-1 agonists and glucose-dependent insulinotropic polypeptide/GLP-1 receptor agonists can attain approximately 8% to 21% weight loss, and bariatric surgery can attain approximately 25% to 30% weight loss. Comprehensive, evidence-based obesity treatment combines behavioral interventions, nutrition, physical activity, pharmacotherapy, and metabolic/bariatric procedures as appropriate for individual patients.
Topics: Adult; Female; Humans; Male; Anti-Obesity Agents; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Gastric Balloon; Glucagon-Like Peptide 1; Glucose; Hypertension; Obesity; Obesity Management; Overweight; Peptides; United States; Weight Loss; Body Mass Index
PubMed: 38015216
DOI: 10.1001/jama.2023.19897 -
Lancet (London, England) Jan 2022Pharmacotherapy provides an option for adults with overweight and obesity to reduce their bodyweight if lifestyle modifications fail. We summarised the latest evidence...
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 143 eligible trials enrolled 49 810 participants. Except for levocarnitine, 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 -7·97, 95% CI -9·28 to -6·66) followed by GLP-1 receptor agonists (OR 6·33, 95% CI 5·00 to 8·00; MD -5·76, 95% CI -6·30 to -5·21). Naltrexone-bupropion (OR 2·69, 95% CI 2·11 to 3·43), phentermine-topiramate (2·40, 1·69 to 3·42), GLP-1 receptor agonists (2·17, 1·71 to 2·77), and orlistat (1·72, 1·44 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 -11·41, 95% CI -12·54 to -10·27).
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; Anti-Obesity Agents; Humans; Network Meta-Analysis; Obesity; Overweight; Randomized Controlled Trials as Topic; Treatment Outcome; Weight Loss
PubMed: 34895470
DOI: 10.1016/S0140-6736(21)01640-8 -
Gastroenterology Nov 2022Pharmacological management of obesity improves outcomes and decreases the risk of obesity-related complications. This American Gastroenterological Association guideline...
BACKGROUND & AIMS
Pharmacological management of obesity improves outcomes and decreases the risk of obesity-related complications. This American Gastroenterological Association guideline is intended to support practitioners in decisions about pharmacological interventions for overweight and obesity.
METHODS
A multidisciplinary panel of content experts and guideline methodologists used the Grading of Recommendations Assessment, Development and Evaluation framework to prioritize clinical questions, identify patient-centered outcomes, and conduct an evidence synthesis of the following agents: semaglutide 2.4 mg, liraglutide 3.0 mg, phentermine-topiramate extended-release (ER), naltrexone-bupropion ER, orlistat, phentermine, diethylpropion, and Gelesis100 oral superabsorbent hydrogel. The guideline panel used the evidence-to-decision framework to develop recommendations for the pharmacological management of obesity and provided implementation considerations for clinical practice.
RESULTS
The guideline panel made 9 recommendations. The panel strongly recommended the use of pharmacotherapy in addition to lifestyle intervention in adults with overweight and obesity (body mass index ≥30 kg/m, or ≥27 kg/m with weight-related complications) who have an inadequate response to lifestyle interventions. The panel suggested the use of semaglutide 2.4 mg, liraglutide 3.0 mg, phentermine-topiramate ER, and naltrexone-bupropion ER (based on moderate certainty evidence), and phentermine and diethylpropion (based on low certainty evidence), for long-term management of overweight and obesity. The guideline panel suggested against the use of orlistat. The panel identified the use of Gelesis100 oral superabsorbent hydrogel as a knowledge gap.
CONCLUSIONS
In adults with overweight and obesity who have an inadequate response to lifestyle interventions alone, long-term pharmacological therapy is recommended, with multiple effective and safe treatment options.
Topics: Adult; Humans; Orlistat; Anti-Obesity Agents; Overweight; Liraglutide; Bupropion; Naltrexone; Topiramate; Weight Loss; Diethylpropion; Phentermine; Obesity; Hydrogels
PubMed: 36273831
DOI: 10.1053/j.gastro.2022.08.045 -
Diabetes & Metabolism Journal Dec 2020Obesity is among the leading causes of morbidity and mortality worldwide and its prevalence continues to increase globally. Because obesity is a chronic, complex, and... (Review)
Review
Obesity is among the leading causes of morbidity and mortality worldwide and its prevalence continues to increase globally. Because obesity is a chronic, complex, and heterogeneous disease influenced by genetic, developmental, biological, and environmental factors, it is necessary to approach obesity with an integrated and comprehensive treatment strategy. As it is difficult to achieve and sustain successful long-term weight loss in most patients with obesity through lifestyle modifications (e.g., diet, exercise, and behavioral therapy), pharmacological approaches to the treatment of obesity should be considered as an adjunct therapy. Currently, four drugs (orlistat, naltrexone extended-release [ER]/bupropion ER, phentermine/topiramate controlled-release, and liraglutide) can be used long-term (>12 weeks) to promote weight loss by suppressing appetite or decreasing fat absorption. Pharmacotherapy for obesity should be conducted according to a proper assessment of the clinical evidence and customized to individual patients considering the characteristics of each drug and comorbidities associated with obesity. In this review, we discuss the mechanisms of action, efficacy, and safety of these available long-term anti-obesity drugs and introduce other potential agents under investigation. Furthermore, we discuss the need for research on personalized obesity medicine.
Topics: Anti-Obesity Agents; Benzazepines; Humans; Orlistat; Phentermine; Weight Loss
PubMed: 33389955
DOI: 10.4093/dmj.2020.0258 -
Handbook of Experimental Pharmacology 2022Older medications approved for chronic weight management (orlistat, naltrexone/bupropion, liraglutide 3 mg and, in the USA, phentermine/topiramate) have not been widely...
Older medications approved for chronic weight management (orlistat, naltrexone/bupropion, liraglutide 3 mg and, in the USA, phentermine/topiramate) have not been widely adopted by health care providers. Those medications produce only modest additional weight loss when used to augment lifestyle intervention. However, semaglutide 2.4 mg weekly has recently emerged and produces much more weight loss - on average 15% weight loss at 1 year. Semaglutide's enhanced efficacy and that its class (GLP-1 receptor analogs) is well-known may result in more clinicians adopting pharmacotherapy. Furthermore, the first dedicated cardiovascular outcome trial powered for superiority testing an anti-obesity medication (SELECT) is underway with semaglutide 2.4 mg. A positive outcome will further promote the concept that weight management should be a primary target for cardiometabolic disease control. In phase 3, tirzepatide and cagrilintide/semaglutide combination are showing promise for even greater weight loss efficacy. Another recently approved medication takes a personalized medicine approach; setmelanotide is approved as a therapy for those with some of the ultra-rare genetic diseases characterized by severe, early onset obesity. This chapter reviews the currently available and anticipated medications for chronic weight management as well as those approved for the genetic and syndromic obesities.
Topics: Anti-Obesity Agents; Humans; Islet Amyloid Polypeptide; Obesity; Phentermine; Weight Loss
PubMed: 34783910
DOI: 10.1007/164_2021_560 -
The Medical Letter on Drugs and... Apr 2021
Topics: Anti-Obesity Agents; Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptides; Humans; Incretins; Obesity; Treatment Outcome; Weight Loss
PubMed: 33830968
DOI: No ID Found -
Current Obesity Reports Mar 2021As a chronic and relapsing disease, obesity impairs metabolism and causes cardiovascular diseases. Although behavioral modification is important for the treatment of... (Review)
Review
PURPOSE OF REVIEW
As a chronic and relapsing disease, obesity impairs metabolism and causes cardiovascular diseases. Although behavioral modification is important for the treatment of obesity, it is difficult to achieve an ideal weight or sustain the process of long-term weight loss. Therefore, the obesity control guidelines strongly recommend lifestyle interventions along with medical treatment for patients who are overweight. There is sufficient evidence supporting that pharmacotherapy in combination with behavior-based interventions can result in significant weight loss and improved cardiometabolism.
RECENT FINDINGS
Recent meta-analyses of new anti-obesity drugs and their weight-loss efficacy have shown that the overall placebo-subtracted weight reduction (%) for at least 12 months ranged from 2.9 to 6.8% for the following drugs: phentermine/topiramate (6.8%), liraglutide (5.4%), naltrexone/bupropion (4.0%), orlistat (2.9%), and lorcaserin (3.1%). However, very recently, on February 13, 2020, the US Food and Drug Administration (FDA) ordered the withdrawal of lorcaserin from markets, as a clinical trial to assess drug safety showed an increased risk of cancer. Currently, the anti-obesity medications that have been approved by the FDA for chronic weight management are orlistat, phentermine/topiramate, naltrexone/bupropion, and liraglutide. However, they are costly and may have adverse effects in some individuals. Therefore, drug therapy should be initiated in obese individuals after weighing its benefits and risks. One of the strategies for long-term obesity control is that anti-obesity medications should be tailored for specific patients depending on their chronic conditions, comorbidities, and preferences.
Topics: Animals; Anti-Obesity Agents; Benzazepines; Bupropion; Humans; Liraglutide; Naltrexone; Obesity; Orlistat; Overweight; Phentermine; Topiramate; United States; United States Food and Drug Administration; Weight Loss
PubMed: 33410104
DOI: 10.1007/s13679-020-00422-w -
EClinicalMedicine Apr 2023Obesity is an epidemic and a public health threat. Medical weight management remains one of the options for the treatment of excess weight and recent advances have... (Review)
Review
UNLABELLED
Obesity is an epidemic and a public health threat. Medical weight management remains one of the options for the treatment of excess weight and recent advances have revolutionized how we treat, and more importantly how we will be treating obesity in the near future. Metreleptin and Setmelanotide are currently indicated for rare obesity syndromes, and 5 other medications (orlistat, phentermine/topiramate, naltrexone/bupropion, liraglutide, semaglutide) are approved for non-syndromic obesity. Tirzepatide is about to be approved, and other drugs, with exciting novel mechanisms of action primarily based on incretins, are currently being investigated in different phases of clinical trials. The majority of these compounds act centrally, to reduce appetite and increase satiety, and secondarily, in the gastrointestinal tract to slow gastric emptying. All anti-obesity medications improve weight and metabolic parameters, with variable potency and effects depending on the specific drug. The currently available data do not support a reduction in hard cardiovascular outcomes, but it is almost certain that such data are forthcoming in the very near future. The choice of the anti-obesity medication needs to take into consideration the patient's clinical and biochemical profile, co-morbidities, and drug contra-indications, as well as expected degree of weight loss and improvements in cardio-renal and metabolic risk. It also remains to be seen whether precision medicine may offer personalized solutions to individuals with obesity, and whether it may represent the future of medical weight management along with the development of novel, very potent, anti-obesity medications currently in the pipeline.
FUNDING
None.
PubMed: 36992862
DOI: 10.1016/j.eclinm.2023.101882 -
Life (Basel, Switzerland) Jul 2023Obesity affects approximately 1 in 5 youth globally and increases the risk of complications during adolescence and young adulthood, including type 2 diabetes,... (Review)
Review
Obesity affects approximately 1 in 5 youth globally and increases the risk of complications during adolescence and young adulthood, including type 2 diabetes, dyslipidemia, hypertension, non-alcoholic fatty liver disease, obstructive sleep apnea, and polycystic ovary syndrome. Children and adolescents with obesity frequently experience weight stigma and have an impaired quality of life, which may exacerbate weight gain. Pediatric obesity is typically defined using sex-, age-, and population-specific body mass index percentiles. Once identified, pediatric obesity should always be managed with lifestyle modification. However, adolescents with obesity may also benefit from anti-obesity medications (AOM), several of which have been approved for use in adolescents by the US Food and Drug Administration, including liraglutide, phentermine/topiramate, and semaglutide. For children with specific, rare monogenic obesity disorders, setmelanotide is available and may lead to significant weight loss. Metabolic and bariatric surgery may be used for the management of severe obesity in youth; though highly effective, it is limited to specialized centers and has had relatively low pediatric uptake. In this narrative review using pediatric-focused data from original research, reviews, clinical practice guidelines, governmental agencies, and pharmaceutical companies, we review obesity-related metabolic complications in youth and management strategies, including AOM and bariatric surgery.
PubMed: 37511966
DOI: 10.3390/life13071591 -
Nature Reviews. Endocrinology Sep 2023Obesity is a common chronic disease in children and adolescents and its prevalence is increasing worldwide. The causes are multifactorial but involve biological... (Review)
Review
Obesity is a common chronic disease in children and adolescents and its prevalence is increasing worldwide. The causes are multifactorial but involve biological predisposition towards a specific body-weight set point and defended adipose tissue mass converging with an obesogenic environment. Comprehensive treatment of paediatric obesity includes lifestyle modification therapy, anti-obesity medications (AOMs) and/or metabolic surgery. Lifestyle modification therapy used alone produces fairly modest weight loss for most youth with obesity. The emergence of new AOMs has changed the landscape of paediatric weight management, improving the outlook for youth with obesity. This Review briefly highlights obesity development pathways in youth and the role that pharmacotherapy can play in counteracting these pathophysiological forces. Here, results from adolescent AOM clinical trials published since 2020 are reviewed, including the safety, efficacy and tolerability of the newest treatments (glucagon-like peptide 1 receptor agonists and phentermine-topiramate). The importance of a comprehensive and chronic care model, including both lifestyle modification and ongoing pharmacotherapy, will be discussed in the context of maximizing long-term health outcomes. Finally, insight will be provided into the emerging pipeline of AOMs (for example, incretin receptor co-agonists and tri-agonists) and how future therapies might fundamentally change the prognosis for youth with obesity.
Topics: Adolescent; Humans; Child; Pediatric Obesity; Topiramate; Fructose; Anti-Obesity Agents; Weight Loss
PubMed: 37337008
DOI: 10.1038/s41574-023-00858-9