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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 -
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 -
Clinical Therapeutics Jul 2023Despite the introduction of various pharmaceutical therapies for treating obesity, selecting the optimal treatment remains challenging for both patients and physicians.... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Despite the introduction of various pharmaceutical therapies for treating obesity, selecting the optimal treatment remains challenging for both patients and physicians. Therefore, in this network meta-analysis (NMA), we aim to simultaneously compare the available drugs for treating obesity to determine the most effective treatment options.
METHODS
International databases, including PubMed, Web of Science, Scopus, Cochrane Library, and Embase, were searched for studies published from database inception to April 2023. The consistency assumption was evaluated using by the loop-specific and design × treatment interaction approaches. The effects of treatment in the NMA were summarized using mean differences based on a change score analysis. The random-effects model was used to report the results. Results were reported with 95% CIs.
FINDINGS
Of 9519 retrieved references, 96 randomized controlled trials, including 68 with both men and women, 23 with women only, and 5 with men only, met the eligibility criteria for this study. There were 4 treatment networks in the trials of both men and women, 4 in the trials of women only, and 1 in the trials of men only. The best-ranked treatments in the network in the trials of both men and women were (1) semaglutide, 2.4 mg (P-score = 0.99); (2) hydroxycitric acid, 4667 mg 3 times daily, supervised walking, and 2000-kcal/d diet (P-score = 0.92); (3) phentermine hydrochloride and behavioral therapy (P-score = 0.92); and (4) liraglutide plus advice to diet and exercise (P-score = 1.00). In women, the best-ranked treatments were beloranib (P-score = 0.98) and sibutramine, metformin, and hypocaloric diet (P-score = 0.90). In men, there was no significant difference among treatments.
IMPLICATIONS
According to the results of this NMA, semaglutide seems to be an effective treatment option for both men and women, whereas beloranib appears to be particularly effective for women with obesity and overweight, but its production has been stopped since 2016 and is not available.
Topics: Male; Humans; Female; Obesity; Diet, Reducing; Network Meta-Analysis; Pharmaceutical Preparations; Randomized Controlled Trials as Topic
PubMed: 37400324
DOI: 10.1016/j.clinthera.2023.06.003 -
Saudi Pharmaceutical Journal : SPJ :... Oct 2023Recently, many drugs have been approved for halting overweight and obesity-few types of research shifted to using Anti-obesity medications (AOM) solely for well-being... (Review)
Review
BACKGROUND
Recently, many drugs have been approved for halting overweight and obesity-few types of research shifted to using Anti-obesity medications (AOM) solely for well-being and shape-keeping.
OBJECTIVE
This narrative review's objective was to explore the use of AOM in relation to their medical indications, efficacy, and cardiovascular safety.
METHODS AND MATERIALS
We have conducted a narrative review of the literature on approved/non-approved AOM used for obesity and overweight. We have shed light on the emerging trials of therapies and evolving remedies.
RESULTS
Recently, there has been an enormous change in the use of AOM with high consumption that deserves extensive surveillance for the long-term consequences and impact on social, mental, and physical health. Nearly six AOMs and combined therapy are approved by the Food and Drug Administration. The recent guidelines for obesity management have shifted the focus from weight loss to goals that the patient considers essential and toward targeting the root cause of obesity.
CONCLUSION
The use of AOM increased enormously despite its sometimes-dubious safety and ineffectiveness. The public and medical professionals should be vigilant to the real-world benefits of anti-obesity drugs and their achieved effectiveness with an improved safety profile.
PubMed: 37712012
DOI: 10.1016/j.jsps.2023.101757 -
Lancet (London, England) Apr 2024Pharmacotherapy provides an option for adults with overweight and obesity to reduce their bodyweight if lifestyle modifications fail. We summarised the latest evidence... (Meta-Analysis)
Meta-Analysis
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 132 eligible trials enrolled 48 209 participants. 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 -7·98, 95% CI -9·27 to -6·69) followed by GLP-1 receptor agonists (OR 6·33, 95% CI 5·00 to 8·00; MD -5·79, 95% CI -6·34 to -5·25). Naltrexone-bupropion (OR 2·69, 95% CI 2·10 to 3·44), phentermine-topiramate (2·40, 1·68 to 3·44), GLP-1 receptor agonists (2·22, 1·74 to 2·84), and orlistat (1·71, 1·42 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 -11·40, 95% CI -12·51 to -10·29).
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; Humans; Overweight; Network Meta-Analysis; Topiramate; Obesity; Weight Loss; Phentermine; Randomized Controlled Trials as Topic
PubMed: 38582569
DOI: 10.1016/S0140-6736(24)00351-9 -
Diabetes, Obesity & Metabolism Sep 2023To compare the benefits and harms of drugs approved for weight management in adults with obesity or overweight. (Meta-Analysis)
Meta-Analysis
AIM
To compare the benefits and harms of drugs approved for weight management in adults with obesity or overweight.
MATERIALS AND METHODS
We performed a systematic review of drugs approved for treating obesity and overweight. We searched MEDLINE, Embase and CENTRAL through 26 February 2023. Random-effects network meta-analysis was applied.
RESULTS
A total of 168 trials (97 938 patients) were included. There was no evidence that drugs approved for weight management had different associations with cardiovascular death (69 trials, 59 037 participants). Naltrexone/bupropion was associated with lower cardiovascular mortality than placebo (odds ratio [OR], 0.62 [95% CI: 0.39, 0.99]; low certainty evidence). All drugs were associated with greater weight loss at 12 months than placebo (33 trials, 37 616 participants), mainly semaglutide (mean difference [MD], -9.02 kg [95% CI: -10.42, -7.63]; moderate certainty) and phentermine/topiramate (MD, -8.10 kg [95% CI: -10.14, -6.05]; high certainty); and with greater waist circumference reduction at 12 months than placebo (24 trials, 35 733 participants), mainly semaglutide (MD, -7.84 cm [95% CI: -9.34, -6.34]; moderate certainty) and phentermine/topiramate (MD, -6.20 cm [95% CI: -7.46, -4.94]; high certainty). Semaglutide and phentermine/topiramate were associated with lower or no difference in the odds of treatment withdrawal compared with all other drugs (87 trials, 70 860 participants).
CONCLUSIONS
Among adults with obesity or overweight, semaglutide and phentermine/topiramate were associated with greater body weight loss and waist circumference reduction at 12 months than all other drugs, and lower or no significant difference in risks of withdrawal. There was no evidence that drugs approved for weight management had different associations with cardiovascular death.
Topics: Adult; Humans; Overweight; Topiramate; Network Meta-Analysis; Randomized Controlled Trials as Topic; Obesity; Phentermine
PubMed: 37254688
DOI: 10.1111/dom.15138 -
Current Organic Synthesis 2024In recent years, a growing global concern has been obesity. Patients with obesity are at major risk for developing a number of diseases. These diseases may significantly... (Review)
Review
In recent years, a growing global concern has been obesity. Patients with obesity are at major risk for developing a number of diseases. These diseases may significantly impact patient's daily lives and increase the mortality rate. Over a year, medication for obesity has undergone substantial changes. An amphetamine-like prescription drug called Phentermine (Adipex-P, Lomaira) is used to suppress appetite. In the last few years, Phentermine and its derivatives have attracted much attention due to their use in weight reduction; by reducing appetite or prolonging the feeling of fullness, it can aid in weight reduction. So, reviewing the synthesis of Phentermine and its derivatives becomes imperative. Therefore, various synthetic routes for Phentermine (from benzaldehyde, isopropyl phenyl ketone, dimethyl benzyl carbinol) and its derivatives synthesis, involving ortho-palladation, are also reviewed here comprehensively.
Topics: Phentermine; Humans; Appetite Depressants
PubMed: 37259208
DOI: 10.2174/1570179420666230530095245 -
Journal of Obesity & Metabolic Syndrome Jun 2023Obesity is a prevalent global health issue affecting approximately half of the world's population. Extensive scientific research highlights the urgent need for effective... (Review)
Review
Obesity is a prevalent global health issue affecting approximately half of the world's population. Extensive scientific research highlights the urgent need for effective obesity management to mitigate health risks and prevent complications. While bariatric surgery has proven to be highly effective, providing substantial short-term and long-term weight loss and resolution of obesity-related comorbidities, it is important to recognize its limitations and associated risks. Given the global obesity epidemic and the limitations of surgical interventions, there is high demand for effective and safe anti-obesity medications (AOMs). In Korea, the Korean Society for the Study of Obesity strongly advocates for the use of pharmacotherapy in Korean adults with a body mass index of 25 kg/m or higher who have not achieved weight reduction through non-pharmacological treatments. Currently, five AOMs have been approved for long-term weight management: orlistat, naltrexone/bupropion, phentermine/topiramate, liraglutide, and semaglutide. Tirzepatide is awaiting approval, and combination of semaglutide/cagrilintide and oral semaglutide are currently undergoing rigorous evaluation in phase 3 clinical trials. Furthermore, other promising drugs, including orforglipron, BI 456906, and retartrutide, are progressing to phase 3 studies, expanding the therapeutic options for obesity management. In personalized patient care, physicians play a crucial role in accurately identifying individuals who genuinely require pharmacotherapy and selecting appropriate AOMs based on individual patient characteristics. By integrating evidence-based interventions and considering the unique needs of patients, healthcare professionals significantly contribute to the success of obesity management strategies.
PubMed: 37349257
DOI: 10.7570/jomes23032