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Current Medicinal Chemistry 2020Obesity represents the second preventable mortality cause worldwide, and is very often associated with type 2 Diabetes Mellitus (T2DM). The first line treatment is...
BACKGROUND
Obesity represents the second preventable mortality cause worldwide, and is very often associated with type 2 Diabetes Mellitus (T2DM). The first line treatment is lifestyle modification to weight-loss, but for those who fail to achieve the goal or have difficulty in maintaining achieved results, pharmacological treatment is needed. Few drugs are available today, because of their side effects.
OBJECTIVE
We aim to review actual pharmacological management of obese patients, highlighting differences between Food and Drug Administration - and European Medicine Agency-approved molecules, and pointing out self-medications readily obtainable and widely distributed.
METHODS
Papers on obesity, weight loss, pharmacotherapy, self- medication and diet-aid products were selected using Medline. Research articles, systematic reviews, clinical trials and meta-analyses were screened.
RESULTS
Anti-obesity drugs with central mechanisms, such as phentermine and lorcaserin, are available in USA, but not in Europe. Phentermine/topiramate and naltrexone/bupropion combinations are now available, even though the former is still under investigation from EMA. Orlistat, with peripheral mechanisms, represents the only drug approved for weight reduction in adolescents. Liraglutide has been approved at higher dose for obesity. Anti-obesity drugs, readily obtainable from the internet, include crude-drug products and supplements for which there is often a lack of compliance to national regulatory standards.
CONCLUSIONS
Mechanisms of weight loss drugs include the reduction of energy intake or the increase in energy expenditure and sense of satiety as well as the decrease of hunger or the reduction in calories absorption. Few drugs are approved, and differences exist between USA and Europe. Moreover, herbal medicines and supplements often sold on the internet and widely used by obese patients, present a risk of adverse effects.
Topics: Adolescent; Anti-Obesity Agents; Diabetes Mellitus, Type 2; Europe; Humans; Obesity; Phentermine
PubMed: 30678612
DOI: 10.2174/0929867326666190124121725 -
American Journal of Therapeutics
Topics: Anti-Bacterial Agents; Colonoscopy; Enterocolitis, Pseudomembranous; Humans; Phentermine
PubMed: 34228655
DOI: 10.1097/MJT.0000000000001068 -
Journal of Medicinal Chemistry Aug 2023The cardiotoxicity associated with -ethyl-dexfenfluramine (norDF) and related agonists of the serotonin receptor 2B (5-HT) has solidified the receptor's place as an... (Review)
Review
The cardiotoxicity associated with -ethyl-dexfenfluramine (norDF) and related agonists of the serotonin receptor 2B (5-HT) has solidified the receptor's place as an "antitarget" in drug discovery. Conversely, a growing body of evidence has highlighted the utility of 5-HT antagonists for the treatment of pulmonary arterial hypertension (PAH), valvular heart disease (VHD), and related cardiopathies. In this Perspective, we summarize the link between the clinical failure of fenfluramine-phentermine (fen-phen) and the subsequent research on the role of 5-HT in disease progression, as well as the development of drug-like and receptor subtype-selective 5-HT antagonists. Such agents represent a promising class for the treatment of PAH and VHD, but their utility has been historically understudied due to the clinical disasters associated with 5-HT. Herein, it is our aim to examine the current state of 5-HT drug discovery, with an emphasis on the receptor's role in the central nervous system (CNS) versus the periphery.
Topics: Humans; Receptor, Serotonin, 5-HT2B; Serotonin; Fenfluramine; Heart Valve Diseases; Drug Discovery
PubMed: 37584406
DOI: 10.1021/acs.jmedchem.3c01178 -
Obesity (Silver Spring, Md.) Jul 2023The study aim was to review the economic evaluation literature of commercially available and effective nonsurgical weight-loss interventions to investigate whether there... (Review)
Review
OBJECTIVE
The study aim was to review the economic evaluation literature of commercially available and effective nonsurgical weight-loss interventions to investigate whether there is evidence to support claims of cost-effectiveness (i.e., good value for money) or cost savings (i.e., a positive return on investment).
METHODS
Relevant databases were systematically reviewed to identify economic evaluations of commercially available weight-loss products and services shown to result in clinically significant weight loss. Five weight-loss medications (orlistat, liraglutide, naltrexone-bupropion, semaglutide, and phentermine-topiramate), two meal replacement programs (Jenny Craig, Optifast), and one behavioral intervention (Weight Watchers [WW]) that met inclusion criteria were identified. After screening, 32 relevant comparisons of cost-effectiveness or cost savings across 20 studies were identified.
RESULTS
Ten of twenty pharmaceutical comparisons showed evidence of cost-effectiveness based on established thresholds. Four of twelve nonpharmaceutical comparisons provided evidence of cost-effectiveness, and five made claims of cost savings. However, methodological concerns cast doubt on the robustness of these claims.
CONCLUSIONS
Evidence of cost-effectiveness for commercially available, evidence-based, nonsurgical weight-loss interventions is mixed. There is no evidence for cost-saving weight-loss medications and only weak evidence for behavioral and weight-loss interventions. Results provide a call to action to generate more robust evidence of the economic value proposition for these interventions.
Topics: Humans; Anti-Obesity Agents; Weight Loss; Orlistat; Cost-Benefit Analysis; Liraglutide
PubMed: 37231621
DOI: 10.1002/oby.23760 -
Romanian Journal of Internal Medicine =... Mar 2024Obesity and overweight are the major risk factors for numerous chronic diseases, including cardiovascular diseases such as heart disease and stroke, which are the... (Review)
Review
Obesity and overweight are the major risk factors for numerous chronic diseases, including cardiovascular diseases such as heart disease and stroke, which are the leading causes of death worldwide. The prevalence of obesity has dramatically risen in both developed and developing countries, making it a significant public health concern and a global crisis. Despite lifestyle modifications being the first-line treatment, the high risk of relapse has led to a growing interest in non-invasive pharmacotherapeutic interventions to achieve and maintain weight loss and reverse the growth of the obesity epidemic. Cardiovascular diseases and cancer account for the highest mortality rates among other comorbidities associated with obesity and overweight. Excess and abnormally deposited adipose tissue secretes various inflammatory mediators, leading to cardiovascular diseases and cancers. Weight loss of 5-10% significantly reduces cardiometabolic risk. Medications currently approved in the USA for long-term management of obesity are orlistat, naltrexone, bupropion, phentermine/topiramate, and Glucagon Like Peptide-1 (GLP-1) agonists such as liraglutide and semaglutide. The benefit-to-risk of medications, comorbidities, and individual responses should guide the treatment decisions. The article provides a comprehensive overview and discussion of several weight loss medications used previously and currently, including their efficacy, mechanisms of action, and side effects.
Topics: Humans; Overweight; Cardiovascular Diseases; Obesity; Anti-Obesity Agents; Weight Loss
PubMed: 37752761
DOI: 10.2478/rjim-2023-0023 -
Current Opinion in Endocrinology,... Apr 2015Overweight and obesity together with their comorbidities have become increasingly prevalent worldwide. The need for well tolerated, effective interventions has become... (Review)
Review
PURPOSE OF REVIEW
Overweight and obesity together with their comorbidities have become increasingly prevalent worldwide. The need for well tolerated, effective interventions has become increasingly urgent. Here we review the pharmacology, benefits, and risks of Western and Chinese medications used for weight loss.
RECENT FINDINGS
Lifestyle interventions for weight loss are efficacious, but have had limited long-term durability. Bariatric surgery is very effective for weight loss and reversal of type 2 diabetes mellitus (T2DM), but it is invasive and not consistently durable in all patients. Recent studies show that newer Western pharmaceuticals and some traditional Chinese medications may be effective for appropriate patients in need of weight loss.
SUMMARY
New Western medications, notably lorcaserin, phentermine/topiramate, naltrexone/bupropion, and liraglutide, are more effective and possibly safer than older medications but have important side-effects. Chinese herbal medicines may have efficacy similar to that of older Western medications and with few side-effects, but data are limited. We suggest that for appropriate patients, in particular those with or at high risk for T2DM, the judicious use of these medications with lifestyle modification is justified. This may be particularly true in Asia where T2DM develops at a low BMI, though more data are needed to support this concept.
Topics: Anti-Obesity Agents; Comorbidity; Drugs, Chinese Herbal; Humans; Obesity; Risk Factors; Risk Reduction Behavior; Treatment Outcome; Weight Loss
PubMed: 25692921
DOI: 10.1097/MED.0000000000000140 -
Endocrinology and Metabolism Clinics of... Sep 2016Successful treatment of obesity requires a multidisciplinary approach including diet, exercise and behavioral modification. As lifestyle changes are not sufficient for... (Review)
Review
Successful treatment of obesity requires a multidisciplinary approach including diet, exercise and behavioral modification. As lifestyle changes are not sufficient for some patients, pharmacologic therapies should be considered as adjuncts to lifestyle interventions. In this article, we review clinical indications, mechanisms of action, dosing/administration, side effects, drug interactions and contraindications for the six most widely prescribed obesity medications. We also summarize the efficacy data from phase 3 trials which led to drug approval. As multiple agents are sometimes required for clinically significant weight loss, the future of obesity medicine will likely involve combinations of agents in addition to behavioral counseling.
Topics: Anti-Obesity Agents; Exercise; Humans; Life Style; Obesity; Weight Loss
PubMed: 27519128
DOI: 10.1016/j.ecl.2016.04.005 -
Expert Opinion on Pharmacotherapy Aug 2020Pharmacotherapy is a useful adjunct when patients with obesity are unable to achieve adequate benefit from lifestyle interventions. (Review)
Review
INTRODUCTION
Pharmacotherapy is a useful adjunct when patients with obesity are unable to achieve adequate benefit from lifestyle interventions.
AREAS COVERED
This review covers the history of antiobesity drugs, efficacy, and risks of currently approved drugs, limits of their usefulness in clinical practice, gaps in knowledge, methodological limitations of clinical trials, and reasons for underutilization.
EXPERT OPINION
In randomized controlled trials, currently approved antiobesity drugs have yielded an average weight loss ranging from approximately 3% to 9% relative to placebo at 1 year. Inadequate inclusion of racial and ethnic minorities and men, and high dropout rates in clinical trials limit generalizability of these findings to clinical practice. Weight loss achieved with antiobesity drugs is generally associated with lowered glycemia, but improvements in blood pressure and lipid measures tend to be marginal. There is limited evidence for sustained weight loss beyond 1 year and for safety and efficacy of antiobesity drugs in children and adolescents, and in post-bariatric surgery patients. None have demonstrated reduction in major adverse cardiovascular events or other significant disease outcomes. Limited health insurance coverage and negative perceptions of physicians have hindered the utilization of antiobesity drugs.
Topics: Adolescent; Anti-Obesity Agents; Bariatric Surgery; Blood Pressure; Child; Clinical Trials as Topic; Drug Combinations; Drug Utilization; Humans; Life Style; Obesity; Treatment Outcome; Weight Loss
PubMed: 32292094
DOI: 10.1080/14656566.2020.1748599 -
Endocrine, Metabolic & Immune Disorders... 2024Obesity is a chronic lifestyle issue with devastating results. Behavioral changes are one of the initial lines of management strategies for obesity, but they are not... (Review)
Review
Obesity is a chronic lifestyle issue with devastating results. Behavioral changes are one of the initial lines of management strategies for obesity, but they are not very efficient management strategies. Many people also use surgical intervention to maintain a healthy weight, now considered to be the most common and effective obesity management. Chemically synthesized medicines fill the gap between lifestyle interventions and minimally invasive surgical management of obesity. The most common issue associated with monotherapy without side effects is its moderate effectiveness and higher dose requirement. Combination therapy is already used for many serious and complicated disease treatments and management and has shown efficacy as well. Generally, we use two or more medicines with different mechanisms of action for a better effect. The commonly used combination therapy for obesity management includes low-dose phentermine and prolonged and slow-releasing mechanism topiramate; naltrexone, and bupropion. Phentermine with inhibitors of Na-glucose cotransporter-2 or glucagon-like peptide-1 (GLP-1) agonists with gastric hormone or Na-glucose cotransporter-2 are two more viable combo therapy. This combination strategy aims to achieve success in bariatric surgery and the scientific community is working in this direction.
Topics: Humans; Obesity; Anti-Obesity Agents; Drug Therapy, Combination; Phentermine; Treatment Outcome; Animals
PubMed: 37641995
DOI: 10.2174/1871530323666230825140808 -
Drug Design, Development and Therapy 2024Anti-obesity medications (AOMs), along with lifestyle interventions, are effective means of inducing and maintaining weight loss in patients with obesity. Although the...
PURPOSE
Anti-obesity medications (AOMs), along with lifestyle interventions, are effective means of inducing and maintaining weight loss in patients with obesity. Although the efficacy of AOMs has been reported, there have been no direct comparisons of these drugs. Therefore, in the present study, we aimed to compare the efficacy of all the AOMs available in Korea in a real-world setting.
PATIENTS AND METHODS
The body weight and composition of 205 adults treated with phentermine, phentermine/topiramate, liraglutide, naltrexone/bupropion, lorcaserin, or orlistat for at least 6 months were analyzed at 2 month intervals. The prevalence of the achievement of a ≥5% weight loss and the changes in body composition were compared between participants using each AOM at each visit.
RESULTS
A total of 132 (64.4%) participants achieved ≥5% weight loss within 6 months (prevalence of ≥5% weight loss after 6 months: phentermine, 87.2%; phentermine/topiramate, 67.7%; liraglutide, 58.1%; naltrexone/bupropion, 35.3%; lorcaserin, 75%; orlistat, 50%). At each visit, after adjustment for age, sex, and baseline body weight, phentermine use was associated with a significantly higher prevalence of ≥5% weight loss than the use of the other AOMs, except for liraglutide. There were significant differences in the body weight, body mass index and body fat mass among the AOM groups by visit (P for interaction <0.05), but not in their waist circumference, skeletal muscle mass, percentage body fat, or visceral fat area.
CONCLUSION
All the AOMs were effective at inducing and maintaining weight loss, in the absence of significant changes in muscle mass, over a 6 month period, and the short-term use of phentermine and the long-term use of phentermine/topiramate or liraglutide would be practical choices for the treatment of obesity. However, further, large-scale studies are necessary to confirm these findings.
Topics: Adult; Humans; Orlistat; Topiramate; Liraglutide; Naltrexone; Bupropion; Fructose; Anti-Obesity Agents; Obesity; Body Weight; Phentermine; Weight Loss
PubMed: 38524878
DOI: 10.2147/DDDT.S445415