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Journal of the American College of... Jan 2018Obesity continues to be among the top health concerns across the globe. Despite our failure to contain the high prevalence of obesity, we now have a better understanding... (Review)
Review
Obesity continues to be among the top health concerns across the globe. Despite our failure to contain the high prevalence of obesity, we now have a better understanding of its pathophysiology, and how excess adiposity leads to type 2 diabetes, hypertension, and cardiovascular disease. Lifestyle modification is recommended as the cornerstone of obesity management, but many patients do not achieve long-lasting benefits due to difficulty with adherence as well as physiological and neurohormonal adaptation of the body in response to weight loss. Fortunately, 5 drug therapies-orlistat, lorcaserin, liraglutide, phentermine/topiramate, and naltrexone/bupropion-are available for long-term weight management. Additionally, several medical devices are available for short-term and long-term use. Bariatric surgery yields substantial and sustained weight loss with resolution of type 2 diabetes, although due to the high cost and a small risk of serious complications, it is generally recommended for patients with severe obesity. Benefit-to-risk balance should guide treatment decisions.
Topics: Anti-Obesity Agents; Bariatric Surgery; Cardiovascular Diseases; Humans; Obesity; Risk Assessment; Risk Factors; Risk Reduction Behavior
PubMed: 29301630
DOI: 10.1016/j.jacc.2017.11.011 -
Lancet (London, England) May 2016A modern approach to obesity acknowledges the multifactorial determinants of weight gain and the health benefits to be derived from weight loss. Foundational to any... (Review)
Review
A modern approach to obesity acknowledges the multifactorial determinants of weight gain and the health benefits to be derived from weight loss. Foundational to any weight loss effort is lifestyle change, diet, and increased physical activity. The approach should be a high quality diet to which patients will adhere accompanied by an exercise prescription describing frequency, intensity, type, and time with a minimum of 150 min moderate weekly activity. For patients who struggle with weight loss and who would receive health benefit from weight loss, management of medications that are contributing to weight gain and use of approved medications for chronic weight management along with lifestyle changes are appropriate. Medications approved in the USA or European Union are orlistat, naltrexone/bupropion, and liraglutide; in the USA, lorcaserin and phentermine/topiramate are also available. Surgical management (gastric banding, sleeve gastrectomy, and Roux-en Y gastric bypass) can produce remarkable health improvement and reduce mortality for patients with severe obesity.
Topics: Anti-Obesity Agents; Bariatric Surgery; Diet, Reducing; Exercise Therapy; Humans; Obesity; Risk Reduction Behavior; Treatment Outcome; Weight Loss
PubMed: 26868660
DOI: 10.1016/S0140-6736(16)00271-3 -
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 -
Metabolism: Clinical and Experimental Mar 2019The obesity epidemic is closely associated with the rising prevalence and severity of nonalcoholic fatty liver disease (NAFLD): obesity has been linked not only with... (Review)
Review
The obesity epidemic is closely associated with the rising prevalence and severity of nonalcoholic fatty liver disease (NAFLD): obesity has been linked not only with simple steatosis (SS), but also with advanced disease, i.e., nonalcoholic steatohepatitis (NASH), NASH-related cirrhosis and hepatocellular carcinoma. As a consequence, apart from increasing all-cause mortality, obesity seems to increase liver-specific mortality in NAFLD patients. Given the lack of approved pharmacological interventions for NAFLD, targeting obesity is a rational option for its management. As the first step, lifestyle modification (diet and exercise) is recommended, although it is difficult to achieve and sustain. When the first step fails, adding pharmacotherapy is recommended. Several anti-obesity medications have been investigated in NAFLD (e.g., orlistat, glucagon-like peptide-1 analogs), other anti-obesity medications have not been investigated (e.g., lorcaserin, phentermine hydrochloric, phentermine/topiramate and naltrexone/bupropion), whereas some medications with weight-lowering efficacy have not been approved for obesity (e.g., sodium-glucose cotransporter-2 inhibitors, farnesoid X receptor ligands). If the combination of lifestyle modification and pharmacotherapy also fails, then bariatric surgery should be considered in selected morbidly obese individuals. This review summarizes best evidence linking obesity with NAFLD and presents related therapeutic options.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Obesity
PubMed: 30502373
DOI: 10.1016/j.metabol.2018.11.014 -
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 -
Metabolic Syndrome and Related Disorders Oct 2018The objective of this review is to examine advances in the development of combination therapies for the treatment of obesity beyond diet or lifestyle interventions.... (Review)
Review
The objective of this review is to examine advances in the development of combination therapies for the treatment of obesity beyond diet or lifestyle interventions. Experimental combination pharmacotherapies include combinations of pramlintide and phentermine as well as amylin and bupropion-naltrexone. Incretin and pancreatic hormones generally inhibit upper gastrointestinal motor functions, and combinations showing efficacy in obesity are coadministration of glucagon-like peptide-1 (GLP-1) with glucagon, a unimolecular dual incretin of PEGylated GLP-1/GIP coagonist, the combination of GLP-1 and PYY, and, in proof of concept studies, combined infusions of GLP-1, peptide YY, and oxyntomodulin. Among bariatric procedures, repeat intragastric balloon (IGB) treatments are more efficacious than IGB plus diet, and endoscopic intervention can enhance the effects of Roux-en-Y gastric bypass when weight regain occurs. A first trial has provided promising results with combination of IGB plus the GLP-1 analog, liraglutide, compared to the balloon alone. Thus, combination therapies for the treatment of obesity hold promise for introduction into clinical practice.
Topics: Animals; Anti-Obesity Agents; Bariatric Surgery; Caloric Restriction; Combined Modality Therapy; Diet, Reducing; Disease Models, Animal; Humans; Obesity; Treatment Outcome; Weight Gain; Weight Loss
PubMed: 29993319
DOI: 10.1089/met.2018.0075 -
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 -
JAMA Jun 2016Five medications have been approved for the management of obesity, but data on comparative effectiveness are limited. (Meta-Analysis)
Meta-Analysis Review
IMPORTANCE
Five medications have been approved for the management of obesity, but data on comparative effectiveness are limited.
OBJECTIVE
To compare weight loss and adverse events among drug treatments for obesity using a systematic review and network meta-analysis.
DATA SOURCES
MEDLINE, EMBASE, Web of Science, Scopus, and Cochrane Central from inception to March 23, 2016; clinical trial registries.
STUDY SELECTION
Randomized clinical trials conducted among overweight and obese adults treated with US Food and Drug Administration-approved long-term weight loss agents (orlistat, lorcaserin, naltrexone-bupropion, phentermine-topiramate, or liraglutide) for at least 1 year compared with another active agent or placebo.
DATA EXTRACTION AND SYNTHESIS
Two investigators identified studies and independently abstracted data using a predefined protocol. A Bayesian network meta-analysis was performed and relative ranking of agents was assessed using surface under the cumulative ranking (SUCRA) probabilities. Quality of evidence was assessed using GRADE criteria.
MAIN OUTCOMES AND MEASURES
Proportions of patients with at least 5% weight loss and at least 10% weight loss, magnitude of decrease in weight, and discontinuation of therapy because of adverse events at 1 year.
RESULTS
Twenty-eight randomized clinical trials with 29 018 patients (median age, 46 years; 74% women; median baseline body weight, 100.5 kg; median baseline body mass index, 36.1) were included. A median 23% of placebo participants had at least 5% weight loss vs 75% of participants taking phentermine-topiramate (odds ratio [OR], 9.22; 95% credible interval [CrI], 6.63-12.85; SUCRA, 0.95), 63% of participants taking liraglutide (OR, 5.54; 95% CrI, 4.16-7.78; SUCRA, 0.83), 55% taking naltrexone-bupropion (OR, 3.96; 95% CrI, 3.03-5.11; SUCRA, 0.60), 49% taking lorcaserin (OR, 3.10; 95% CrI, 2.38-4.05; SUCRA, 0.39), and 44% taking orlistat (OR, 2.70; 95% CrI, 2.34-3.09; SUCRA, 0.22). All active agents were associated with significant excess weight loss compared with placebo at 1 year-phentermine-topiramate, 8.8 kg (95% CrI, -10.20 to -7.42 kg); liraglutide, 5.3 kg (95% CrI, -6.06 to -4.52 kg); naltrexone-bupropion, 5.0 kg (95% CrI, -5.94 to -3.96 kg); lorcaserin, 3.2 kg (95% CrI, -3.97 to -2.46 kg); and orlistat, 2.6 kg (95% CrI, -3.04 to -2.16 kg). Compared with placebo, liraglutide (OR, 2.95; 95% CrI, 2.11-4.23) and naltrexone-bupropion (OR, 2.64; 95% CrI, 2.10-3.35) were associated with the highest odds of adverse event-related treatment discontinuation. High attrition rates (30%-45% in all trials) were associated with lower confidence in estimates.
CONCLUSIONS AND RELEVANCE
Among overweight or obese adults, orlistat, lorcaserin, naltrexone-bupropion, phentermine-topiramate, and liraglutide, compared with placebo, were each associated with achieving at least 5% weight loss at 52 weeks. Phentermine-topiramate and liraglutide were associated with the highest odds of achieving at least 5% weight loss.
Topics: Anti-Obesity Agents; Bayes Theorem; Benzazepines; Drug Combinations; Female; Fructose; Humans; Lactones; Liraglutide; Male; Middle Aged; Naltrexone; Obesity; Orlistat; Phentermine; Randomized Controlled Trials as Topic; Topiramate; Weight Loss
PubMed: 27299618
DOI: 10.1001/jama.2016.7602