Role of the Gastroenterologist in Managing Obesity

John K DiBaise; Amy E Foxx-Orenstein

Disclosures

Expert Rev Gastroenterol Hepatol. 2013;7(5):439-451. 

In This Article

Treatment of Obesity

The goal of weight loss is to improve or eliminate obesity-related comorbidities and decrease their future risk. Data from numerous prospective, randomized controlled trials demonstrate that reductions as modest as 5% initial weight improve many of the comorbidities associated with obesity. Following an appropriate medical evaluation and assessment of weight loss readiness, a structured, goal-oriented treatment plan is recommended allowing for realistic goals, regular follow-up and long-term care. Alterations in dietary intake and physical activity, together with behavioral modification therapy, are the cornerstones of treatment. Pharmacotherapy and bariatric surgery may be useful in selected patients. Because many patients who are seen by gastroenterologists are overweight or obese, it is important for gastroenterologists to be familiar with options available to treat obesity and to consider becoming actively involved in helping their obese patients lose weight.

Diet, Activity and Behavioral Approaches

An ideal diet would decrease body fat while preserving lean mass, would be readily attainable and effective in maintaining lost weight, would reduce obesity-related morbidity and improve quality of life.[54] A reduction in caloric intake by 500–1,000 kcal daily has been shown to induce a weight loss of 1–2 pounds/week.[55,56] For most individuals, this can be accomplished by limiting portion size, reducing the energy density of the meal, distributing meals throughout the day and reducing late night eating. Such a diet typically amounts to 1,000–1,200 kcal/day for women and 1,500–2,000 kcal/day for men. Extreme diets, while producing rapid weight loss, often result in metabolic imbalance, nutrient deficiencies and, importantly, have a high failure rate. Adherence to the diet plan plays a key role in any successful weight control program.

Differences in diet macronutrient distribution (e.g., low fat vs low carbohydrate vs high protein) have been suggested to influence weight loss success, at least over the short term; however, recent evidence suggests no difference when adhered to over the longer term,[57] although other beneficial effects on lipids may still occur.[58] There is insufficient data to determine overall effect of whole grain fiber on weight loss. Ultimately, it is the reduction in overall calorie intake that results in clinically meaningful weight loss. Nevertheless, dietary composition may affect weight loss maintenance via its effects on energy expenditure.[59]

Behavioral modification to control weight involves the sum of all of the practices that influence calorie intake and calorie expenditure.[60] This approach helps an individual decide what to change and how to change by facilitating self-monitoring, stimulus control, goal setting and problem solving. Behavioral modification has been demonstrated to independently produce weight loss of 8–10% during the first 6 months of treatment.[60] Meal replacement may further increase the magnitude of weight loss,[61] suggesting that increasing structure may improve dietary compliance. Nevertheless, commercial weight loss programs that incorporate such practices have been associated with high cost and attrition rates and a high probability of regaining 50% or more of lost weight after 2 years.[62]

Physical activity is recommended as a component of weight management strategies to prevent weight gain, to lose weight and to prevent weight gain after weight loss.[63] Although the benefits of physical activity for a healthy lifestyle are clear, there has never been consensus as to what constitutes an optimal physical activity program. Moderate-intensity aerobic physical activity (e.g., brisk walk, elliptical) 30 to 60 min five-times/week is recommended to prevent weight gain. Importantly, while of benefit in reducing body fat and increasing muscle mass, this degree of activity will provide only modest weight loss, if any, unless coupled with moderate diet restriction.[64] The addition of resistance training to aerobic activity does not seem to add much with regards to reductions in visceral and liver fat, aminotransferase levels or fasting insulin resistance.[65]

Pharmacologic Therapy

Along with diet, exercise and behavior modification, drug therapy may be a helpful adjunct in the treatment of overweight and obese patients.[66] Appetite and satiation are regulated by complex and incompletely understood central serotonergic, dopaminergic, opioid and cannabinoid systems that, together with many interconnections, affect a number of regulatory pathways.[67] Until recently, pharmacologic options to manage overweight and obesity have been limited due to concerns about efficacy and safety. Because most patients regain their weight when these drugs are stopped, long-term use is required, emphasizing the importance of long-term safety. As such, if patients do not lose a moderate amount of weight (i.e., expect about 5% after 12 weeks) or experience weight regain while on treatment, the medication should be stopped. At present, pharmacologic options are considered adjunctive therapy in obese and overweight patients with a BMI >27 kg/m2 with weight-related comorbidities.[68] The recent approval of two new medications provides an opportunity for gastroenterologists to take a more proactive approach to managing their overweight and obese patients.

Phentermine, an amphetamine derivative, is one of several sympathomimetic amine anorexiants approved by US FDA as a short-term weight loss aid. These agents are thought to stimulate the central release of dopamine and norepinephrine, leading to a suppression of appetite and increasing satiation.[67]

Despite great enthusiasm from clinicians and patients toward the use of medications to treat obesity, only three drugs are FDA-approved for long-term use (Table 2), and numerous drugs have been withdrawn from the market or abandoned in the development stage because of serious adverse effects, including aminorex (pulmonary hypertension), fenfluramine and dexfenfluramine (cardiac valvulopathy), phenylpropanolamine (stroke), rimonabant (suicidal ideation) and, most recently, sibutramine (myocardial infarction and stroke).

Until recently, the gastric and pancreatic lipase inhibitor, orlistat, has been the only drug approved for long-term use. Orlistat (Xenical, Roche), FDA-approved in 1999, inhibits the absorption of fat by about 30% at the recommended dose of 120 mg three-times/day with meals and has been shown to lead to a sustained 5–10% total body weight loss in most patients.[69] Benefits in lipids, blood pressure and glycemic control have also been described. A nonprescription formulation is also available. The predominant side effects of orlistat are gastrointestinal including borborygmi, cramping, flatulence and anal seepage with oily discharge. These side effects tend to occur early and subside as patients learn how to avoid these problems by avoiding high fat diets and sticking to the recommended dietary intake of 30% fat. As malabsorption of fat-soluble vitamins may also occur, vitamin supplementation is recommended.

A relationship between higher levels of serotonin in the brain and lower appetite has been appreciated for years. Due to the development of serious side effects, however, the use of serotonergic drugs (e.g., fenfluramine, dexfenfluramine, sibutramine) has proven problematic for long-term weight control. Nevertheless, the highly selective 5-hydroxytryptamine 2C receptor agonist, lorcaserin (Belviq, Arena Pharmaceuticals) was approved by the FDA in June 2012 for the long-term treatment of obesity. In two pivotal trials of lorcaserin, the cumulative proportion of patients who achieved weight loss 5% over 12 months was 47% for lorcaserin versus 23% for placebo.[70] Favorable changes in lipids, blood pressure, glycemic control and waist circumference were also seen. Although there were initially safety concerns including an increased incidence of mammary and brain tumors in rats and cardiac valvulopathy in earlier studies in humans, these concerns have subsequently been allayed leading to lorcaserin's recent approval. Lorcaserin is contraindicated in pregnancy and while breastfeeding.

Topiramate is an FDA-approved anticonvulsant and migraine prevention therapy that has well-known, anti-craving and weight loss effects. Despite a denial of approval by the FDA in 2010, earlier this year, the FDA approved the fixed-dose combination of phentermine and topiramate (Qsymia, Vivus Pharmaceuticals) for the long-term treatment of obesity based on new safety and efficacy data. The rationale for use of a combination of medications is that it allows for lower doses of the individual agents, thus potentially resulting in fewer side effects. In a recent randomized, placebo-controlled pivotal trial of phentermine-topiramate, the proportion of patients who achieved weight loss 5% over 12 months with the higher dose of the active drug was 67% compared to 17% with the placebo.[71] The higher dose group also had significantly greater changes relative to placebo for waist circumference, blood pressure, fasting glucose and lipids. The most common adverse events were paresthesia, dry mouth, constipation, dysgeusia and insomnia. Potential safety concerns with phentermine-topiramate include teratogenicity and resting tachycardia. Accordingly, the approval of this drug combination required a risk evaluation and mitigation strategy that includes a medication guide, patient brochure and formal training program for prescribers.

Weight fluctuation, up or down, is an unwanted side effect of a number of medications; weight gain is a major cause of drug nonadherence. Indeed, many antidepressants, antipsychotics, antidiabetic and antihypertensive agents, corticosteroids and antihistamine promote weight gain.[72] Weight management measures should be implemented when prescribing drugs known to cause weight gain, with strong consideration given to alternatives whenever available.

Bariatric Surgery

At present, bariatric surgery is the only obesity treatment that consistently achieves and maintains substantial weight loss, decreases the incidence and severity of obesity-related comorbidities, and improves overall quality of life and survival.[73,74] Current criteria for patient selection for bariatric surgery date back to an NIH Consensus Statement from 1991 and include individuals with a BMI >40 kg/m2 or >35 kg/m2 if obesity-related comorbidities exist, who have failed other means of weight loss and are psychologically stable and able to make the diet, exercise and behavioral changes necessary to maintain long-term success after surgery.[75] Bariatric options include the adjustable gastric band (AGB), the vertical sleeve gastrectomy, the Roux-en-Y gastric bypass and the biliopancreatic diversion (BPD) with or without a duodenal switch (DS).[76] The FDA recently approved the AGB for use in those with a BMI >30 kg/m2 with an obesity-related comorbidity. The growing obesity epidemic together with the promulgation of guidelines regarding patient selection and the widespread adoption of laparoscopy to perform these surgeries has led to tremendous growth in the performance of bariatric operations.[77] Although RYGB is the most commonly performed bariatric operation in the United States and is generally considered the 'gold standard' bariatric surgery at present, each operation has advantages and disadvantages.[78] Important considerations for the patient and surgeon alike in the decision to proceed with bariatric surgery include the technical aspects of the operation, magnitude of initial and sustained weight loss desired, correction of obesity-related comorbidities and postoperative complications including long-term nutritional problems. Although the mechanism of weight loss with these operations tends to rely on restriction of food intake, malabsorption of ingested food, or a combination of the two, the exact mechanism(s) appears to be more complex implicating hormonal, inflammatory, CNS and gut microbial factors.[79,80]

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