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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 -
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 -
Children (Basel, Switzerland) Dec 2022Obesity might adversely affect the health and well-being of children and their families. Childhood obesity has crucial implications for health, both during childhood and... (Review)
Review
Obesity might adversely affect the health and well-being of children and their families. Childhood obesity has crucial implications for health, both during childhood and as they age. It is highly associated with many acute problems and is commonly present during childhood, making visits and hospital admissions polarized in this group of children. The problems that may affect these children can be medical, such as asthma, chronic inflammation, orthopedic abnormalities, liver disease, diabetes mellitus or dyslipidemia. Long-term consequences of cardiovascular risk factors, the persistence of obesity and premature mortality are common among adults who had obesity during their early lives. Additionally, they could also suffer from psychological issues, such as low self-esteem, which puts them at risk of a much more serious psychosocial problem that may lead to depression, as well as a disruption in educational achievements and social relationships. A healthy diet, physical activity, adequate sleep, and limited screen time are all preventive measures that should be implemented at the family and community levels, preferably through well-structured programs. Furthermore, pharmacological management of childhood obesity is limited and only used after non-pharmacological interventions have failed or in the late stages of obesity. However, recent guidelines advocate the early use of medical interventions. Approved pharmacotherapeutic options include orlistat, phentermine/topiramate combination and liraglutide. There are several other options approved primarily for other specific forms of obesity or for other indications, including setmelanotide, metformin, lisdexamfetamine, zonisamide and fluoxetine. Bariatric surgery is a safe and effective option in cases with extreme obesity and comorbidities considering the need for long-term monitoring and support for cases and their families post-surgery. This review aims to discuss and highlight the recent evidence regarding risk factors, clinical consequences, prevention, and treatment of childhood obesity.
PubMed: 36553418
DOI: 10.3390/children9121975 -
Current Hypertension Reports Feb 2019Weight loss is strongly associated with improvement in blood pressure; however, the mechanism of weight loss can impact the magnitude and sustainability of blood... (Review)
Review
PURPOSE OF REVIEW
Weight loss is strongly associated with improvement in blood pressure; however, the mechanism of weight loss can impact the magnitude and sustainability of blood pressure reduction.
RECENT FINDINGS
Five drugs-orlistat, lorcaserin, liraglutide, phentermine/topiramate, and naltrexone/bupropion-are currently approved for weight loss therapy in the USA. Naltrexone/bupropion results in an increase in in-office and ambulatory blood pressure compared to placebo. Other therapies are associated with modest lowering of blood pressure, and are generally well-tolerated; nonetheless, evidence is limited regarding their effect on blood pressure, particularly longitudinally, in individuals with hypertension. Although weight loss medications can be an effective adjunct to lifestyle modifications in individuals with obesity, there is limited evidence regarding their benefit with regard to blood pressure. Future studies evaluating the effectiveness of weight loss medications should include careful assessment of their short- and long-term impact on blood pressure in individuals with hypertension.
Topics: Anti-Obesity Agents; Blood Pressure Monitoring, Ambulatory; Humans; Hypertension; Obesity; Weight Loss
PubMed: 30747357
DOI: 10.1007/s11906-019-0915-1 -
Current Opinion in Endocrinology,... Feb 2021Childhood obesity is escalating globally. Lifestyle and behavioral changes, which are the frequently used interventions in clinical practice, lead to only modest... (Review)
Review
PURPOSE OF REVIEW
Childhood obesity is escalating globally. Lifestyle and behavioral changes, which are the frequently used interventions in clinical practice, lead to only modest improvements in children with established obesity. Bariatric surgery is currently the most effective obesity treatment but has very limited utilization in pediatric obesity and is preferentially used for children with worsening comorbidities. There exists a massive treatment gap for children suffering with obesity especially after the failure of lifestyle modifications. Pharmacotherapy that is an established management tool in adults is very infrequently used in children. Only two medications, Phentermine and Orlistat are approved by the Food and Drug Administration (FDA) for use in adolescent obesity. Herein, we discuss the current landscape and available literature on the use of antiobesity pharmacotherapy in children.
RECENT FINDINGS
There are emerging pediatric data about the efficacy of the many weight loss medications that are FDA approved in adults. Moreover, more clinical trials are underway on the rarer, intractable forms of obesity such as monogenic, syndromic, and hypothalamic obesity.
SUMMARY
Weight loss medications in children, like adults, have variable efficacy and similar side effect profiles. Rigorous research and improved education of providers about weight loss medications may address the huge treatment gap in severe pediatric obesity.
Topics: Anti-Obesity Agents; Child; Humans; Pediatric Obesity; Weight Loss
PubMed: 33186194
DOI: 10.1097/MED.0000000000000587 -
Obesity (Silver Spring, Md.) Apr 2021Little is known about the predictors of response to obesity interventions.
OBJECTIVE
Little is known about the predictors of response to obesity interventions.
METHODS
In 450 participants with obesity, body composition, resting energy expenditure, satiety, satiation, eating behavior, affect, and physical activity were measured by validated studies and questionnaires. These variables were used to classify obesity phenotypes. Subsequently, in a 12-month, pragmatic, real-world trial performed in a weight management center, 312 patients were randomly assigned to phenotype-guided treatment or non-phenotype-guided treatment with antiobesity medications: phentermine, phentermine/topiramate, bupropion/naltrexone, lorcaserin, and liraglutide. The primary outcome was weight loss at 12 months.
RESULTS
Four phenotypes of obesity were identified in 383 of 450 participants (85%): hungry brain (abnormal satiation), emotional hunger (hedonic eating), hungry gut (abnormal satiety), and slow burn (decreased metabolic rate). In 15% of participants, no phenotype was identified. Two or more phenotypes were identified in 27% of patients. In the pragmatic clinical trial, the phenotype-guided approach was associated with 1.75-fold greater weight loss after 12 months with mean weight loss of 15.9% compared with 9.0% in the non-phenotype-guided group (difference -6.9% [95% CI -9.4% to -4.5%], P < 0.001), and the proportion of patients who lost >10% at 12 months was 79% in the phenotype-guided group compared with 34% with non-phenotype-guided treatment group.
CONCLUSIONS
Biological and behavioral phenotypes elucidate human obesity heterogeneity and can be targeted pharmacologically to enhance weight loss.
Topics: Anti-Obesity Agents; Clinical Trials as Topic; Female; Humans; Male; Obesity; Precision Medicine; Weight Loss
PubMed: 33759389
DOI: 10.1002/oby.23120