Weight Loss Strategies for Treatment of Obesity Kushner, Robert F
Progress in cardiovascular diseases,
2014, January-February 2014, 2014 Jan-Feb, 2014-1-00, Letnik:
56, Številka:
4
Journal Article
Recenzirano
Abstract Obesity is one of the most serious and prevalent non-communicable diseases of the 21st century. It is also a patient-centered condition in which affected individuals seek treatment through a ...variety of commercial, medical and surgical approaches. Considering obesity as a chronic medical disease state helps to frame the concept of using a three-stepped intensification of care approach to weight management. As a foundation, all patients should be counseled on evidence-based lifestyle approaches that include diet, physical activity and behavior change therapies. At the second tier, two new pharmacological agents, phentermine–topiramate and lorcaserin, were approved in 2012 as adjuncts to lifestyle modification. The third step, bariatric surgery, has been demonstrated to be the most effective and long-term treatment for individuals with severe obesity or moderate obesity complicated by comorbid conditions that is not responsive to non-surgical approaches. By using a medical model, clinicians can provide more proactive and effective treatments in assisting their patients with weight loss.
Obesity is one of the most serious and prevalent non-communicable diseases of the twenty-first century. It is also a patient-centered condition in which affected individuals seek treatment through a ...variety of commercial, medical and surgical approaches. Considering obesity as a chronic medical disease state helps to frame the concept of using a three-stepped intensification of care approach to weight management. As a foundation, all patients should be counseled on evidence-based lifestyle approaches that include diet, physical activity and behavior change therapies. At the second tier, four new pharmacological agents, lorcaserin, phentermine/topiramate, naltrexone/bupropion and liraglutide have been approved since 2012 as adjuncts to lifestyle modification. The third step, bariatric surgery, has been demonstrated to be the most effective and long-term treatment for individuals with severe obesity or moderate obesity complicated by co-morbid conditions that is not responsive to non-surgical approaches. By using a medical model, clinicians can provide more proactive and effective treatments in assisting their patients with weight loss.
Severe obesity and its related diseases, such as type 2 diabetes, hypertension, dyslipidemia, and sleep apnea, are very common in the United States, but currently very few patients with these ...conditions choose to undergo bariatric surgery. Summaries of the expanding evidence for both the benefits and risks of bariatric surgery are needed to better guide shared decision-making conversations.
There are approximately 252 000 bariatric procedures (per 2018 numbers) performed each year in the US, of which an estimated 15% are revisions. The 1991 National Institutes of Health guidelines recommended consideration of bariatric surgery in patients with a body mass index (calculated as weight in kilograms divided by height in meters squared) of 40 or higher or 35 or higher with serious obesity-related comorbidities. These guidelines are still widely used; however, there is increasing evidence that bariatric procedures should also be considered for patients with type 2 diabetes and a body mass index of 30 to 35 if hyperglycemia is inadequately controlled despite optimal medical treatment for type 2 diabetes. Substantial evidence indicates that surgery results in greater improvements in weight loss and type 2 diabetes outcomes, compared with nonsurgical interventions, regardless of the type of procedures used. The 2 most common procedures used currently, the sleeve gastrectomy and gastric bypass, have similar effects on weight loss and diabetes outcomes and similar safety through at least 5-year follow-up. However, emerging evidence suggests that the sleeve procedure is associated with fewer reoperations, and the bypass procedure may lead to more durable weight loss and glycemic control. Although safety is a concern, current data indicate that the perioperative mortality rates range from 0.03% to 0.2%, which has substantially improved since early 2000s. More long-term randomized studies are needed to assess the effect of bariatric procedures on cardiovascular disease, cancer, and other health outcomes and to evaluate emerging newer procedures.
Modern bariatric procedures have strong evidence of efficacy and safety. All patients with severe obesity-and especially those with type 2 diabetes-should be engaged in a shared decision-making conversation about the risks and benefits of surgery compared with continuing usual medical and lifestyle treatment, and the decision about surgery should be driven primarily by informed patient preferences.
Objective
The obesity epidemic is a public health concern, warranting further research into pharmacological treatments for weight management (WM) as an adjunct to lifestyle interventions. The ...Semaglutide Treatment Effect in People with obesity (STEP) program aims to investigate the effect of semaglutide versus placebo on weight loss, safety, and tolerability in adults with obesity or overweight.
Methods
Across five phase 3 trials (NCT03548935, WM; NCT03552757, WM in type 2 diabetes; NCT03611582, WM with intensive behavioral therapy; NCT03548987, sustained WM; and NCT03693430, long‐term WM), ~5,000 participants are being randomly assigned to receive semaglutide 2.4 mg once weekly subcutaneously versus placebo. Results will be available in 2020/2021. For all trials, the primary end point is change from baseline to end of treatment in body weight.
Results
Participants have a mean age of 46.2 to 55.3 years, are mostly female (mean: 74.1%‐81.0%), and have a mean BMI of 35.7 to 38.5 kg/m2 and a mean waist circumference of 113.0 to 115.7 cm.
Conclusions
The STEP program evaluates the efficacy and safety of semaglutide 2.4 mg subcutaneously once weekly in a broad population. The trials will provide insights on WM in people with obesity with and without type 2 diabetes and on long‐term follow‐up.
Nearly half of Americans are projected to have obesity by 2030, underscoring the pressing need for effective treatments. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) represent the first ...agents in a rapidly evolving, highly promising landscape of nascent hormone-based obesity therapeutics. With the understanding of the neurobiology of obesity rapidly expanding, these emerging entero-endocrine and endo-pancreatic agents combined or coformulated with GLP-1 RAs herald a new era of targeted, mechanism-based treatment of obesity. This article reviews GLP-1 RAs in the treatment of obesity and previews the imminent future of nutrient-stimulated hormone-based anti-obesity therapeutics.
Abstract
The prevalence of obesity, measured by body mass index, has risen to unacceptable levels in both men and women in the United States and worldwide with resultant hazardous health ...implications. Genetic, environmental, and behavioral factors influence the development of obesity, and both the general public and health professionals stigmatize those who suffer from the disease. Obesity is associated with and contributes to a shortened life span, type 2 diabetes mellitus, cardiovascular disease, some cancers, kidney disease, obstructive sleep apnea, gout, osteoarthritis, and hepatobiliary disease, among others. Weight loss reduces all of these diseases in a dose-related manner-the more weight lost, the better the outcome. The phenotype of "medically healthy obesity" appears to be a transient state that progresses over time to an unhealthy phenotype, especially in children and adolescents. Weight loss is best achieved by reducing energy intake and increasing energy expenditure. Programs that are effective for weight loss include peer-reviewed and approved lifestyle modification programs, diets, commercial weight-loss programs, exercise programs, medications, and surgery. Over-the-counter herbal preparations that some patients use to treat obesity have limited, if any, data documenting their efficacy or safety, and there are few regulatory requirements. Weight regain is expected in all patients, especially when treatment is discontinued. When making treatment decisions, clinicians should consider body fat distribution and individual health risks in addition to body mass index.
This Scientific Statement critically reviews the definition of obesity, providing a list of assessment methods, obesity-related diseases, and prevention measures.
Overweight and obesity have reached epidemic levels in the United States and worldwide, and this has contributed to substantial cardiovascular and other health risks. However, controversy exists ...concerning the causes of obesity and effective modalities for its prevention and treatment. There is also controversy related to the concept of metabolically healthy obesity phenotype, the "obesity paradox," and on the importance of fitness to protect individuals who are overweight or obese from cardiovascular diseases. In this state-of-the-art review, the authors focus on "healthy weight" with the emphasis on the pathophysiologic effects of weight gain on the cardiovascular system; mechanistic/triggering factors; and the role of preventive actions through personal, education/environment, and societal/authoritative factors, as well as factors to provide guidance for caregivers of health promotion. Additionally, the authors briefly review metabolically healthy obesity, the obesity paradox, and issues beyond lifestyle consideration for weight loss with medications and bariatric surgery.
In addition to building resilience, I have shifted a considerable amount of my counseling from focusing on weight management to stressing the value of good health and well-being, including ...establishing a daily schedule for self-care, choosing nutritious foods, scheduling daily physical activity, getting adequate sleep, destressing, and virtually connecting with friends and family. ...prior to fully transforming our paradigm of how we deliver obesity care, we ultimately will need a rigorous evaluation of all aspects of a newly proposed model, including randomized controlled trials to assess the value of and methods to build resilience, the clinical effectiveness of telemedicine, and resultant long-term outcomes on body weight and other health metrics. Alencar MK, Johnson K, Mullur R, Gray V, Gutierrez E, Korosteleva O. The efficacy of a telemedicine-based weight loss program with video conference health coaching support.
Obesity is a global health challenge with few pharmacologic options. Whether adults with obesity can achieve weight loss with once-weekly semaglutide at a dose of 2.4 mg as an adjunct to lifestyle ...intervention has not been confirmed.
In this double-blind trial, we enrolled 1961 adults with a body-mass index (the weight in kilograms divided by the square of the height in meters) of 30 or greater (≥27 in persons with ≥1 weight-related coexisting condition), who did not have diabetes, and randomly assigned them, in a 2:1 ratio, to 68 weeks of treatment with once-weekly subcutaneous semaglutide (at a dose of 2.4 mg) or placebo, plus lifestyle intervention. The coprimary end points were the percentage change in body weight and weight reduction of at least 5%. The primary estimand (a precise description of the treatment effect reflecting the objective of the clinical trial) assessed effects regardless of treatment discontinuation or rescue interventions.
The mean change in body weight from baseline to week 68 was -14.9% in the semaglutide group as compared with -2.4% with placebo, for an estimated treatment difference of -12.4 percentage points (95% confidence interval CI, -13.4 to -11.5; P<0.001). More participants in the semaglutide group than in the placebo group achieved weight reductions of 5% or more (1047 participants 86.4% vs. 182 31.5%), 10% or more (838 69.1% vs. 69 12.0%), and 15% or more (612 50.5% vs. 28 4.9%) at week 68 (P<0.001 for all three comparisons of odds). The change in body weight from baseline to week 68 was -15.3 kg in the semaglutide group as compared with -2.6 kg in the placebo group (estimated treatment difference, -12.7 kg; 95% CI, -13.7 to -11.7). Participants who received semaglutide had a greater improvement with respect to cardiometabolic risk factors and a greater increase in participant-reported physical functioning from baseline than those who received placebo. Nausea and diarrhea were the most common adverse events with semaglutide; they were typically transient and mild-to-moderate in severity and subsided with time. More participants in the semaglutide group than in the placebo group discontinued treatment owing to gastrointestinal events (59 4.5% vs. 5 0.8%).
In participants with overweight or obesity, 2.4 mg of semaglutide once weekly plus lifestyle intervention was associated with sustained, clinically relevant reduction in body weight. (Funded by Novo Nordisk; STEP 1 ClinicalTrials.gov number, NCT03548935).
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