Katherine H. Saunders

White Paper AGA: POWER — Practice Guide on Obesity and Weight Management, Education, and Resources

&NA; The epidemic of obesity continues at alarming rates, with a high burden to our economy and society. The American Gastroenterological Association understands the importance of embracing obesity as a chronic, relapsing disease and supports a multidisciplinary approach to the management of obesity. Because gastrointestinal disorders resulting from obesity are more frequent and often present sooner than type 2 diabetes mellitus and cardiovascular disease, gastroenterologists have an opportunity to address obesity and provide an effective therapy early. Patients who are overweight or obese already fill gastroenterology clinics with gastroesophageal reflux disease and its associated risks of Barrett’s esophagus and esophageal cancer, gallstone disease, nonalcoholic fatty liver disease/nonalcoholic steatohepatitis, and colon cancer. Obesity is a major modifiable cause of diseases of the digestive tract that frequently goes unaddressed. As internists, specialists in digestive disorders, and endoscopists, gastroenterologists are in a unique position to play an important role in the multidisciplinary treatment of obesity. This American Gastroenterological Association paper was developed with content contribution from Society of American Gastrointestinal and Endoscopic Surgeons, The Obesity Society, Academy of Nutrition and Dietetics, and North American Society for Pediatric Gastroenterology, Hepatology and Nutrition, endorsed with input by American Society for Gastrointestinal Endoscopy, American Society for Metabolic and Bariatric Surgery, American Association for the Study of Liver Diseases, and Obesity Medicine Association, and describes POWER: Practice Guide on Obesity and Weight Management, Education and Resources. Its objective is to provide physicians with a comprehensive, multidisciplinary process to guide and personalize innovative obesity care for safe and effective weight management.

Pharmacotherapy for Obesity

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.

Metformin: an Old Therapy that Deserves a New Indication for the Treatment of Obesity.

Metformin is not currently used for weight loss or diabetes prevention because it lacks an FDA indication for obesity and/or pre-diabetes treatment. Based on the evidence, metformin has been shown to decrease the incidence of type 2 diabetes, and compares favorably to other weight-loss medications in terms of efficacy as well as safety. Thus, metformin should be considered for a treatment indication in patients with these conditions.

Practical Use of Pharmacotherapy for Obesity

Obesity management requires a multidisciplinary approach, as there are many factors that contribute to the development of obesity, as well as the preservation of excess weight once it has been gained. Diet, exercise, and behavior modification are key components of treatment. In addition to lifestyle changes, weight gain secondary to medications is an important modifiable risk factor. Even after appropriate lifestyle modification, and medication adjustments (where possible) to avoid agents that can contribute to weight gain, many patients are still unable to achieve clinically meaningful weight loss. Pharmacotherapy for obesity management can fill an important role for these patients. This article will review medications that can lead to weight gain and potential alternatives, currently approved anti-obesity medications and best practices to individualize the selection process, and the use of testosterone in men with hypogonadism and obesity.

An update on naltrexone/bupropion extended-release in the treatment of obesity

ABSTRACT Introduction: As the prevalence of obesity continues to increase, the need for effective long-term treatment strategies for overweight and obesity is critical. Pharmacology fills a large treatment gap between behavioral therapy, which is insufficient for the majority of patients, and devices and surgery, which are available to only a subset of patients. Naltrexone HCl and bupropion HCl Extended-Release (naltrexone XR/bupropion XR) was approved by the Food and Drug Administration for chronic weight management in 2014. Areas covered: This review illustrates the efficacy and safety of naltrexone XR/bupropion XR by examining data from clinical trials. It also provides an overview of the market and presents the pharmacodynamics and pharmacokinetics of naltrexone and bupropion. Expert opinion: The efficacy and safety profile of naltrexone XR/bupropion XR makes it a viable option for many patients who could benefit from its distinctive mechanism. The medication was shown to produce additive weight loss when combined with an intensive behavioral modification program and it may improve food cravings and eating behaviors. Compared to the other three antiobesity medications approved since 2012, naltrexone XR/bupropion XR is neither a controlled substance nor an injectable agent.

Pharmacotherapy for obesity in individuals with type 2 diabetes

ABSTRACT Introduction: Type 2 diabetes (T2DM) is associated with significant morbidity and mortality. Obesity is one of the main risk factors for T2DM and its management requires a multidisciplinary approach, which may include pharmacotherapy. Areas covered: In this paper, data on efficacy, tolerability and safety of FDA-approved pharmacotherapies for obesity (orlistat, phentermine/topiramate extended-release, lorcaserin, bupropion sustained release/naltrexone sustained release and liraglutide) are reviewed, focusing on individuals with type 2 diabetes. Expert opinion: Obesity is the major pathophysiologic driver of T2DM; conversely 5–10% weight loss leads to significant improvement in glycemic control, lipids and blood pressure. Weight loss maintenance is difficult with lifestyle interventions alone and may require adjunctive therapies. There is good evidence for the efficacy and tolerability of approved anti-obesity pharmacotherapies in individuals with T2DM, with current cardiovascular safety data being most favorable for liraglutide, orlistat and lorcaserin. Given the link between obesity and T2DM, a weight-centric therapeutic approach including use of weight reducing anti-diabetic therapies, and anti-obesity pharmacotherapies is both intuitive and rational to improve glycemic and other metabolic outcomes in patients with T2DM.

Current concepts in management of weight regain following bariatric surgery

ABSTRACT Introduction: Although bariatric surgery is the most effective and durable treatment for obesity, weight regain is common. Areas covered: In this article, we have critically reviewed data from retrospective and prospective studies pertaining to prevalence and predictors of weight regain following bariatric surgery, as well as the utility of behavioral and pharmacotherapeutic interventions to address post-surgical weight regain. Expert commentary: The initial step in management of post-surgical weight regain is a comprehensive evaluation of the patient including a thorough assessment of contributing factors. While lifestyle interventions including diet, exercise and behavior modification are fundamental, they have limited efficacy which can be enhanced by pharmacotherapy. The optimal time to commence pharmacotherapy may be at weight plateau to maximize weight loss outcomes after bariatric surgery. Further prospective studies are needed to determine the best combination of behavioral and pharmacological therapies, and also the timing of pharmacotherapeutic intervention.

The impact of food order on postprandial glycaemic excursions in prediabetes

Data suggest that nutrient order during a meal significantly impacts postprandial glucose and insulin excursions in type 2 diabetes, while its effects in prediabetes have not been reported. Fifteen participants with prediabetes consumed the same meal on 3 days in random order: carbohydrate first, followed 10 minutes later by protein and vegetables (CF); protein and vegetables first, followed 10 minutes later by carbohydrate (PVF); or vegetables first followed by protein and carbohydrate (VF). Blood was sampled for glucose and insulin measurements at 0, 30, 60, 90, 120, 150 and 180 minutes. Incremental glucose peaks were similarly attenuated by >40% in the PVF and VF meal conditions compared with CF. The incremental area under the curve for glucose was 38.8% lower following the PVF meal order, compared with CF, and postprandial insulin excursions were significantly lower in the VF meal condition compared with CF. The CF meal pattern showed marked glycaemic variability whereas glucose levels were stable in the PVF and VF meal conditions. Food order presents a novel, simple behavioural strategy to reduce glycaemic excursions in prediabetes.

Effect of Food Order on Ghrelin Suppression

Data suggest that the temporal sequence of carbohydrate ingestion during a meal has a significant impact on postprandial glucose (1–3), insulin, and glucagon-like peptide 1 (GLP-1) excursions (4) in type 2 diabetes, while the effects on ghrelin suppression and satiety have not been reported. The study design and methods have previously been described in detail (4). Briefly, using a crossover design, 16 subjects with overweight/obesity and metformin-treated type 2 diabetes were assigned to consume the same meal on 3 days in random order: Blood was sampled for glucose, insulin, active GLP-1, and total ghrelin measurements at baseline (just before meal ingestion) and at 30-min intervals up to 180 min. Participants rated their hunger and fullness levels using a visual analog …

Devices and Endoscopic Bariatric Therapies for Obesity

Purpose of ReviewIn this review, we describe the FDA-approved and investigational devices and endoscopic bariatric therapies for the treatment of obesity. We focus on literature published in the past few years and present mechanisms of action as well as efficacy and safety data.Recent FindingsDevices and endoscopic procedures are emerging options to fill the significant treatment gap in the management of obesity. Not only are these devices and procedures minimally invasive and reversible, but they are potentially more effective than antiobesity medications, often safer for poor surgical candidates and possibly less expensive than bariatric surgery.SummaryAs many patients require a variety of management strategies (medications, devices, procedures, and/or surgery) in addition to lifestyle modifications to achieve clinically significant weight loss, the future of obesity treatment involves a multidisciplinary approach. Combinations of advanced treatment strategies can lead to additive or synergistic weight loss. This is an area that requires further investigation.