Obesity Treatment & Management

Although obesity in itself is associated with increased morbidity and mortality, massive, poorly monitored weight loss and/or weight cycling can have equally dire consequences. Among the important potential complications to watch out for in the setting of weight loss are cardiac arrhythmias; electrolyte derangements, of which hypokalemia is the most important; hyperuricemia; and psychologic sequelae, including depression and the development of eating disorders (particularly binge-eating disorders).

The 3 major phases of any successful weight-loss program are as follows:

• Preinclusion screening phase
• Definitive weight-loss program
• Maintenance phase, which can conceivably last for the rest of the patient's life but which must last for at least 2 years after the weight-loss program is completed

Before enrolling any patient in a weight-loss program, the clinician must have a clear idea of that individual’s expectations. Patients with unrealistic expectations should not be enrolled until these are changed to realistic and attainable goals.

Also crucial is a clear assessment of the patient's level of motivation regarding the dietary, exercise, and behavioral changes required to maintain weight loss. This assessment should be completed before the patient is enrolled in a weight-loss program. Comprehensive, written, informed consent must be obtained and should address details of the expected weight loss and the required changes.

Because of the potential harm of attempting weight loss in an unsuitable candidate, all patients to be enrolled in any surgical, medical, or other weight-loss program must be exhaustively screened for underlying psychiatric, psychologic, and/or eating disorders.

Although many of the psychologic and psychiatric problems commonly associated with obesity are not contraindications to enrollment in a weight-loss program, clinicians and patients must be aware of these problems before enrollment. In addition, the clinician must ensure that any such problems are relatively stable, quiescent, or well managed before the patient begins a weight-loss program.

The national weight-loss database tracks indices and predictors in individuals with a sustained (≥5y) weight loss of 15% or greater. The data indicate that sustained compliance with diet programs is by far a more important predictor of sustained weight loss than are consistently increased levels of physical activity. Caloric deficits are more important than any specific composition of dietary macronutrient.

According to a study by Blüher et al, patients regaining weight after initial weight loss on long-term dietary intervention continued to show long-lasting improvements in high-sensitivity C-reactive protein, adiponectin, fetuin, high-density lipoprotein cholesterol, progranulin, and vaspin, suggesting delayed effects of initial weight loss and/or continuous beneficial effects from switching to healthier diets.^[39]

Comorbidities

The management of obesity is not complete without attention being paid to various potential comorbidities. Addressing these issues can have profound effects on the patient's well-being and risk of morbidity and mortality.

A reasonable goal for weight loss in the setting of a medical treatment program is approximately 0.9-1.5 kg/wk. The concept that the weight-loss goal for each subject must be individualized and cannot be unilaterally based on standard weight-for-height norms is becoming increasingly apparent.

One must consider the family's weight, as well as the patient's weight and cultural, ethnic, and racial background, in setting individualized goals of weight loss. A study of approximately 200 obese black women, the Obesity Reduction Black Intervention Trial (ORBIT), found evidence that greater weight loss can be achieved with a culturally adapted weight-loss program than with a more general health program.^[40]

The women in the study were randomly divided into a general health program or a 6-month, culturally adapted program aimed at altering the women's dietary and physical activity patterns (followed by 1 year of maintenance intervention). Women in the latter group lost significantly more weight than did participants in the general program, although the report also found that, despite this success, the average weight loss in the culturally adapted program was still relatively modest and that the amount of weight loss varied greatly among the women in the program.

Like all chronic medical conditions, effective management of obesity must be based on a partnership between a highly motivated patient and a committed team of health professionals, including the physician, psychologist or psychiatrist, physical and exercise therapists, dietitians, and other subspecialists, depending on the comorbidities of the individual patient.

After successful weight loss, the hormones that encourage weight regain remain elevated and do not reach levels recorded before diet-induced weight loss. Thus, long-term strategies are needed to prevent obesity relapse.^[41]

The results of most weight-loss programs are dismal. On average, participants in the best programs lose approximately 10% of their body weight, but people generally regain two thirds of the weight lost within a year.

When defined as sustained weight loss over a 5-year follow-up period, the success of even the best medical weight-loss programs is next to nil. Most available data indicate that, irrespective of the method of medical intervention, 90-95% of the weight lost is regained in 5 years.

Commercially available weight loss programs are more successful and more affordable compared with primary care practice–based programs led by specialty trained staff.^[42]

Weight-loss goals

In general, body weight and body fat generally tenaciously regulated. Available data suggest that a loss of approximately 10% of body weight in subjects who are obese (BMI < 40) is associated with virtually maximal benefits regarding obesity-elated comorbidities; therefore, further attempts at weight loss beyond this level are generally spurred by cosmetic considerations that may be not only unrealistic but also potentially dangerous. This possibility is the basis of a shift in paradigms in the medical management of obesity from a goal of massive weight loss to a goal of maintaining the highest weight possible while still eliminating obesity-related comorbidities or reducing them to minimum.

A study by Rock et al found that a structured weight loss program resulted in greater risk reduction than did usual care.^[43]

In cases of childhood obesity,^{[44, 45, 46]} the goal is to reduce the rate of weight gain to fit the profile expected based on normal growth curves. The intent is not to cause weight loss. The basic principles of management include:

• Modifying diet
• Increasing appropriate physical activity and exercise
• Reducing time spent in sedentary activities (eg, watching television)
• Modifying behavior

Added to these principles is medication therapy. However, such therapy is still rudimentary in the management of pediatric obesity, and a close combination with all the aforementioned modalities is required to achieve substantial and sustained weight loss. At the present, orlistat is the only medication the US Food and Drug Administration (FDA) has approved for use as an adjunct for weight loss in adolescents.

Starvation is a caloric intake of less than 200 kcal/day and is not medically indicated. Starvation is potentially dangerous and can lead to clinically significant starvation ketosis; electrolyte derangements; vitamin, mineral, and other micronutrient deficiencies; and a marked potential for morbidity and mortality. Starvation is not validated as an effective method of achieving substantial and sustained weight loss.

Achieving a caloric deficit is still the most important component to achieving sustained weight loss. However, the considerable variance in individual energy expenditures and compliances to calorie-deficient plans make it difficult to reliably predict how much weight an individual subject may lose.

Among the caveats is the fact that energy expenditure is related to body weight; about 22 kcal/kg of energy is required for basal maintenance of 1 kg of weight in a typical adult. Therefore, obese subjects tend to reduce their energy expenditure as they lose weight, dampening the effect of caloric deficits as weight loss progresses.

Presumably because of their greater lean mass proportions, men tend to lose more weight than women do when caloric deficits are similar.

Because of their lowered energy expenditure, older subjects have increased difficulty in achieving sustained weight loss. The estimated reduction in energy expenditure is 100kcal per decade after the age of 30 years.

Dennis et al found that in overweight and obese middle-aged and older adults on a hypocaloric diet, drinking water before each main meal aided weight loss. In 48 adults aged 55-75 years with a BMI of 25-40 kg/m², those who consumed 500mL of water prior to each daily meal had a 44% greater decline in weight over 12 weeks than did individuals on a hypocaloric diet without premeal water consumption.^[47]

Water drinking could assist weight loss in overweight children. Drinking 10 mL/kg of cold water could result in an additional weight loss of about 1.2 kg/y. This is primarily achieved through water-induced increase in resting energy expenditure.^[48]

Very–low-calorie diets (VLCDs) are best used in an established, comprehensive program. VLCDs involve reducing caloric intake to 800kcal/day or less. When used in optimal settings, they can achieve a weight loss of 1.5-2.5 kg/wk, with a total loss of as much as 20 kg over 12 weeks. No good-quality evidence suggests that a daily calorie intake of less than 800 kcal/d achieves any additional weight loss.

Use special caution whenever VLCDs are prescribed to children, adolescents, or elderly subjects. Use is contraindicated in pregnancy and in protein-wasting states; clinically significant cardiac, renal, hepatic, psychiatric, or cerebrovascular disease; or any other chronic disease. VLCDs are associated with profound initial weight loss, much of which is from lean mass loss in the first few weeks. However, this loss rapidly ceases, and weight-loss velocity then flattens.

Although these diets associated with notable short-term weight loss sometimes less than 15% of baseline weight and although they are associated with improved blood pressure and glycemic control, they cannot be sustained for longer than 3-6 months. Compliance beyond a few weeks is poor, and close supervision is required to avoid mishaps.

Unless a long-term maintenance calorie-deficit program is developed and adhered to, recidivism after the diet is stopped is rapid. Most individuals quickly regain all of the weight they lost and often gain more.

Among the major complications to monitor are hair loss, skin thinning, hypothermia, cholelithiasis, and electrolyte derangement. VLCDs have little or no utility in long-term weight management and are probably best used as stop-gap measures before bariatric surgery or a long-term, comprehensive weight-loss program in patients with very severe or morbid obesity and associated comorbidities (BMI ≥50).

Conventional diets can be broadly classified as follows:

• Balanced, low-calorie diets (or reduced portion sizes)
• Low-fat diets
• Low-carbohydrate diets
• Midlevel diets (eg, Zone diet, in which the 3 major macronutrients [fat, carbohydrate, protein] are eaten in similar proportions of 30-40%)
• Fad diets

Balanced, low-calorie diets and reduced-portion size diets

Balanced, low-calorie diets and reduced-portion size diets are the types that dietitians and other weight-management professionals most commonly prescribe. These diets underlie most of the popular, commercial weight-loss programs, such as those advocated by Jenny Craig, Weight Watchers, Take Off Pounds Sensibly (TOPs), and Overweight Anonymous. The basic premise involves obtaining a detailed dietary inventory of the person, which is used to estimate his or her mean daily caloric intake.

A reasonable goal for the caloric deficit is based on the new goal for total daily calories. Meal plans are then devised to provide this total in 3 or more divided meals throughout the day. Although the meals may be based on regular, everyday foods (with which strategies for effective reduction of portion sizes become central), meal-replacement shakes, bars, prepackaged meals, frozen entrees, and other meals also have adequate amounts of the major macronutrients based on the food pyramid from the US Department of Agriculture and recommended daily allowances (RDAs). These sources also have adequate micronutrients and trace elements. Because alcohol, sodas, most fruit juices, and highly concentrated sweets are generally calorie dense and nutrient deficient (empty calories), these are generally prohibited or reduced to the minimum.

Low-calorie diets involve a caloric intake of 800-1200kcal/d and are associated with a mean weight loss of 0.4-0.5 kg/wk, with a total loss of 6-8 kg in ideal settings. With any low-calorie diet, maintaining an intake of protein with a high biologic value of 1 g/kg or more is vital to preserving lean body mass. Major potential complications to watch for include vitamin deficiency, starvation ketosis, electrolyte derangements, and cholelithiasis. Although these diets are useful for short-term weight loss, none alone is associated with reliable, sustained weight loss.

Normal-calorie diets

Normal-calorie diets involve diets with a caloric intake of greater than 1200 cal/d. The aim of this type of diet is to reduce the caloric intake by 500-1000kcal/day from the patient's current dietary intake. The suggested composition for the best-validated dietary programs are protein intake of 0.8-1.5g/kg of body weight (not to exceed 100 g/d), 10-30% of total calories from fat (preferably ≥90% as polyunsaturated fat and < 10% as saturated fat), carbohydrate intake of 50g/day or more, and water intake of 1L or more. Ensure that the dietary plan provides adequate micronutrients and macronutrients based on the RDAs.

Low-carbohydrate diets

Low-carbohydrate diets have become popular in the past few decades, with the Atkins diet being the most popular. Little rigorous scientific data supports the use of the Atkins diet. It is a high-protein and/or high-fat, very-low-carbohydrate diet that induces ketosis. The very-low-carbohydrate content is critical in inducing short-term weight loss in the first 2-4 weeks; this is largely due to fluid mobilization.

Ketone bodies tend to be generated with daily dietary carbohydrate intake of under 50g, and sodium diuresis is forced, causing most of the short-term weight loss. No robust data about the safety or long-term effectiveness of this diet are available. The premise of the diet is that caloric intake as protein is less prone to fat storage than is the equivalent caloric intake as carbohydrate; however, no physiologic data support this premise.

Data on the long-term effects of a high-protein diet in rodents cause concern because they indicate that these diets may be associated with a reduced life span and a predisposition to neoplasia.

In 2 randomized trials, weight loss with Atkins-type diets was compared with conventional low-fat or balanced calorie-deficit diets. Although the Atkins-type diet had the greatest initial weight loss, weight loss became similar within 1 year. Furthermore, although lipids did not appear to be deleteriously affected, follow-up was only about 1 year, and the noncompliance rate in the Atkins-type group was close to 50%.

The South Beach diet is another low-carbohydrate diet. This program is more liberal in its carbohydrate allowance than the Atkins diet is; therefore, compliance rates are enhanced. The South Beach diet distinguishes between what are considered to be good and bad carbohydrates on the basis of their glycemic index. Although the relevance and importance of the glycemic index is controversial, the diet encourages increased fiber intake, which is associated with lowered weight even when total caloric intake is relatively unchanged. Low-glycemic index diets plus a modest increase in protein intake are better at helping to maintain weight loss.^[49]

Persons who decide to use a low-carbohydrate diet should choose heart-healthy sources of fat (monounsaturated fats, polyunsaturated fats, and fats rich in omega 3 fatty acids, rather than saturated fat) and protein (fish, nuts, legumes, and lean poultry, rather than pork chops, steak, and mutton).

Comparison of diet programs

Dansinger and colleagues compared the Zone, Ornish, and Atkins diets and a typical balanced, calorie-restricted (Weight Watchers) diet.^[50] The Ornish diet, very-low-fat diet, and Atkins diet had the poorest compliance rates. The researchers observed no significant differences in weight loss based on the diet. Compliance and caloric deficits were more important predictors of weight loss and improvement in cardiovascular risk surrogates than was specific dietary composition.

However, another study found low-carbohydrate and low-fat diets to be equally efficacious in inducing weight loss. The study also found that fuel partitioning may impact cardiovascular markers differently.^[51]

When types of diets are compared, low-fat diets are better than low-carbohydrate diets in achieving sustained weight loss (probably because of generally improved compliance).

Before receiving an exercise-program prescription, patients should undergo screening for cardiovascular and respiratory adequacy. Any clinically significant anomalies found require full evaluation by appropriate subspecialist physicians, and only after these issues are adequately managed and stabilized should an active exercise program be begun.^[52]

Aerobic isotonic exercise is of the greatest value for subjects who are obese. The ultimate minimum goal should be to achieve 30-60 minutes of continuous aerobic exercise 5-7 times per week.

Anaerobic isometric exercise, including resistance training, can be cautiously added as an adjunct after the aerobic goal described above is achieved.

Exercise is vital to any weight-management program because it helps to build muscle mass, increasing metabolic activity of the whole-body mass. Exercise also helps to reduce body-fat proportions and decreases the amount of compensatory muscle-mass loss that is typical in the setting of weight loss. Although most laypersons may be unable to sustain enough regular exercise to achieve weight loss, consistent, moderate exercise is important in maintaining weight and in improving overall cardiorespiratory fitness.^[53]

A study by Goodpaster et al showed that patients with severe obesity who introduced exercise concurrently with or after dietary intervention had significant weight loss and modification of cardiometabolic risk factors.^[54] Furthermore, a study by Hankinson et al indicated that benefits of exercise in young age may translate into benefits beyond, particularly in young women.^[55] This information is useful for patients and physicians who may be discouraged by the patients’ initial inability to engage in exercise.

A study by Rejeski et al indicated that community weight-loss and physical activity programs can have a positive impact on mobility in elderly people who are overweight/obese and are in poor cardiovascular health.^[56]

This treatment requires a trained professional to have an in-depth discussion with the patient regarding the changes required, subsequent to a detailed inventory of the patients' daily activities. This inventory is used to identify activities, cues, circumstances, and practices that favor nonmeal eating and snacking. An individualized plan to change these practices is then developed in conjunction with the subject. The effectiveness of this modality depends on a highly motivated patient and a dedicated counselor who is willing to maintain long-term follow-up.^{[57, 58]}

A sufficient amount of human sleep favorably impacts the maintenance of fat-free mass during times of decreased energy intake. In contrast, insufficient sleep undermines the body's ability to limit expansion of fat mass. A healthy sleep pattern is therefore important to harness weight loss benefits from other interventions.^[59]

Not many medications are available for the treatment of obesity, and those that are available have minimal long-term effectiveness.^{[60, 61, 62]}

The increasing knowledge that has come on the heels of the discovery of leptin by Friedman and colleagues in 1994 has spurred a whirlwind of research, with several potential pharmaceuticals now being evaluated in various phases of clinical trial.

The major groups of drugs used to manage obesity are (1) centrally acting medications that impair dietary intake, (2) medications that act peripherally to impair dietary absorption, and (3) medications that increase energy expenditure.

Standards for the development of obesity medications are necessarily high because most persons who are obese are fairly healthy in the short-term and must take these medications for extended periods (possibly for the rest of their lives).

The history of obesity medications is replete with numerous disasters that have taught us caution in the use of this group of medicines. Among the initial medications used for obesity management were amphetamine, methamphetamine, and phenmetrazine. These were all withdrawn because of their high potential for abuse.

Other former antiobesity medications include thyroid hormone (which caused hyperthyroidism, with its attendant sequelae), dinitrophenol (which caused cataracts and neuropathy), rainbow pills (which are a mixture of digitalis and diuretics [which caused deaths from arrhythmias and electrolyte derangements]), aminorex (which caused pulmonary hypertension), and collagen-based VLCDs (which caused sudden deaths).

Additional drugs that were, are, or may in the future be used against obesity or that have been investigated as antiobesity medications include the following:

• Orlistat - The only FDA-approved antiobesity drug on the market; orlistat (Xenical) blocks the action of pancreatic lipase, reducing triglyceride digestion and, thus, absorption^[63] (2 major clinical trials showed sustained weight loss of 9-10% over 2 years)
• D-fenfluramine - Was withdrawn because of problems with cardiac valvulopathies and primary pulmonary hypertension
• Fluoxetine - Not approved for use in achieving weight loss but has been known to cause minimal weight loss as an adverse effect, which is sometimes exploited
• Fenfluramine - Although effectively used in combination with phentermine, fenfluramine was withdrawn in 1997 (along with D-fenfluramine) because of the potential for adverse cardiac, valvular, and pulmonary hypertensive effects; the combination of fenfluramine and phentermine was used in some long-term trials with fair results
• Diethylpropion (25 mg TID) and phentermine - Are available in the United States for short-term use
• ·Phendimetrazine (30 mg/d) and benzphetamine (20-50 mg TID) are no longer available in the United States
• Mazindol - Withdrawn from the US market in 2001; was for only short-term use (1 mg TID)
• Phenylpropanolamine – An alpha-adrenoreceptor agonist that was for short-term use (25 mg TID) but that was recalled from the US market; some reports suggested a potential association between the use of phenylpropanolamine and ischemic stroke (therefore, this drug should be used with caution in elderly individuals and only after carotid atherosclerosis has been excluded)
• Methylphenidate - Not approved by the FDA for obesity management, although several anecdotal reports have described it as having variable success for this purpose^[64]
• Bupropion - Licensed for use as an antidepressant and in smoking cessation but is also associated with minimal to moderate weight loss^[65] (preliminary reports have suggested similar findings with venlafaxine)

Sibutramine

Sibutramine (Meridia) is a centrally acting appetite suppressant that inhibits reuptake of noradrenalin, serotonin, and dopamine.^[66] The Sibutramine Trial of Obesity Reduction and Maintenance (STORM) revealed that a 9% weight loss persisted for as long as 18 months after the start of therapy. However, sibutramine is fraught with adverse cardiovascular outcomes.^[67]

On October 8, 2010, Abbott and the FDA announced that sibutramine was being withdrawn from the market because of increased risk of myocardial infarction and stroke. Europe had suspended sibutramine from the market earlier that year.

The FDA requested the market withdrawal after reviewing data from the Sibutramine Cardiovascular Outcomes Trial (SCOUT). SCOUT was initiated as part of a postmarket requirement to look at the cardiovascular safety of sibutramine after the European approval of this drug. In patients who took the drug, the trial demonstrated a 16% increase over placebo in the risk of serious heart events, including nonfatal myocardial infarction, nonfatal stroke, the need to be resuscitated once the heart stopped, and death. A very small difference (2.5%) in weight loss was noted between the placebo group and the group that received sibutramine.^[68]

Ephedrine and caffeine

Ephedrine and caffeine are second-line options in the medical management of obesity. They both act by increasing energy expenditure, but they are associated with the potential for tachycardia, hypertension, and palpitations. These medications are associated with more weight loss when used in combination than when used alone. They cause 25-40% of their weight loss by inducing thermogenesis, but they also decrease food intake, which accounts for 60-75% of the weight-loss effect.

Topiramate

Topiramate, licensed as an adjunctive antiepileptic agent, has been associated with profound weight loss (as much as 15-18% of the baseline weight). The amount of weight loss appears to be greater with greater baseline weights. The exact mechanism of this effect is being actively investigated. Although the degree of efficacy is exciting, the propensity for adverse effects, especially CNS effects such as drowsiness, paresthesias, memory loss, and confusion, is concerning.

Doses for weight management are lower than those for seizure management (usually 25-100 mg/d in divided doses). Doses of more than 200 mg/d are rarely tolerated when administered for weight loss. Topiramate does not have an FDA-approved indication for weight loss at this time.^[69]

The combination of low-dose phentermine and topiramate in conjunction with office-based lifestyle intervention might improve the success rate in the treatment of obesity.^[70]

Selective serotonin reuptake inhibitors

Although not FDA approved for this purpose, several selective serotonin reuptake inhibitors (SSRIs; eg, fluoxetine, paroxetine) may cause anorexia as one of their major adverse effects. Some of these medications have been used as adjuncts in the medical management of obesity, with variable success.

Cannabinoid-receptor antagonists

The importance of the central cannabinoid system in the understanding and management of feeding disorders has increased.^{[71, 72, 73, 74]} In particular, activation of the cannabinoid type 1 (CB1) receptor is associated with increased appetite and appears to be the basis for the effectiveness of dronabinol in enhancing diet in patients with acquired immunodeficiency syndrome (AIDS) and other wasting syndromes.

CB1-receptor antagonists showed great potential for weight management in several human trials. Rimonabant, the most-developed CB1-receptor antagonist, caused a mean weight loss of 3-6 kg over a 1-year follow-up at doses of 5-20 mg/d. Adverse effects, which were most prevalent at high doses, included dizziness, mood swings, headaches, nausea, vomiting, and diarrhea.

Catechin

A Japanese study found evidence that beverages containing high amounts of catechin, a flavonoid found in green tea, may aid in preventing obesity.^[75] Patients in the investigation, all of whom had type 2 diabetes mellitus, ingested either 582.8 mg or 96.3 mg of catechins per day, by drinking green tea. By the 12th week, participants receiving the higher catechin dose had undergone a significantly greater reduction in waist circumference than did patients receiving the lower dose.

Other potential antiobesity agents

Agents in early phases of investigation that may yet prove of use against obesity include ghrelin antagonists, alpha-MSH analogs, enterostatin, neuropeptide YY antagonists, beta3-adrenergic agonists, and various nutraceuticals and herbal products (including an extract from the African cactus Hoodia gordonii, which may cause clinically significant appetite suppression).

Metformin does not have an indication for obesity, but it was useful in preventing diabetes and improving insulin resistance in conditions such as polycystic ovary syndrome [PCOS]. Its use was associated with weight neutrality or mild weight loss.^[76]

Gadde and colleagues reported that randomized use of the antiepileptic drug zonisamide in a cohort of 60 obese subjects was associated with a weight loss of about 6% of baseline weight, with few adverse effects,^[77] while Lustig and colleagues reported the potential utility of octreotide in ameliorating the distinct subclass of hypothalamic obesity.^[78]

The first glucagon-like peptide (GLP)-1 analog, exenatide, although not FDA approved for obesity management, has been associated with modest weight loss in subjects with type 2 diabetes.

Peptide YY (3-36) is being developed as a nasal inhaler. Preliminary, ongoing phase 1 and 2 trials yielded encouraging results.^{[79, 80, 81]}

Amylin is the synthetic version of pramlintide and does not have an FDA indication for obesity management. However, this drug is clearly associated with variable weight loss in people with type 1 or 2 diabetes, while improving overall glycemic control.

Drugs no longer used

Some agents that initially showed promise were later demonstrated to be poor prospects in rigorous randomized intervention trials. These include the following:

• Guar gum
• Chitosan
• Axokine - Or ciliary neurotrophic factor, the use of which was associated with the development of autoantibodies and marked reduction in anorexiant potency in about 30% of subjects
• Leptin - Still used in cases of the rare obesity subclass leptin-deficient obesity
• St. John's wort
• Psyllium
• Conjugated linoleic acid
• Chromium
• Ginseng

One strategy to prevent obesity that is being explored in the dietary industry involves the use of fat substitutes.

Olestra (Olean) has been approved for use as a dietary supplement and additive in various foods, such as potato chips and crackers. Olestra has a calorie value of 0 kcal/g, whereas fat has approximately 9.1 kcal/g. Olestra consists of a sucrose polyester backbone with 6-8 fatty-acid side chains; this structure makes the molecule too large for digestive enzymes of the gut to hydrolyze.

In many trials, olestra had fairly good tolerability, although it apparently is less tasty than materials cooked in regular fat. The major adverse effects reported were flatulence, bloating, diarrhea, and loose stools. Because of concerns regarding the possible malabsorption of fat-soluble vitamins, the FDA requires all olestra-prepared foods to be supplemented with these vitamins.

Sitostanol (Benecol) is a plant stanol ester preparation that is used as a spread similar to margarine. It blocks cholesterol absorption in the intestine, with no clinically significant alterations occurring in triglyceride or HDL-C values.

Preliminary reports suggest the potential utility of agents that impede dietary carbohydrate absorption. Tagatose is one of the compounds in this class that is undergoing trials.

Surgical therapy for obesity(bariatric surgery) is the only available therapeutic modality associated with clinically significant and sustained weight loss in subjects with morbid obesity associated with comorbidities. Evidence shows that well-performed bariatric surgery in carefully selected patients and a good multidisciplinary support team substantially ameliorate the morbidities associated with severe obesity.

Although bariatric surgery is the only therapeutic method associated with consistently demonstrable sustained weight loss, it is expensive, highly procedure and surgeon specific, and certainly not the solution for the burgeoning obesity epidemic.

Patient selection for bariatric procedures must be addressed along the same stringent lines as those discussed earlier for the selection of patients for medical weight-management programs.

The presence of comorbidities is not a contraindication to bariatric surgical procedures; however, the patient's condition must be stabilized and adequately treated before surgery. At a minimum, consider these procedures only in subjects with a BMI greater than 40 kg/m² and/or a weight greater than 45 kg above the age-defined and sex-defined ideal weight. For subjects with BMIs of 35-40 kg/m², several other comorbidities must be present to justify these procedures.

Comorbidities that have been reported to be ameliorated and/or resolved through bariatric surgery include the following:

• Type 2 diabetes mellitus
• Hypertension
• Heart failure
• Peripheral edema
• Respiratory insufficiency
• Asthma
• Dyslipidemia
• Esophagitis
• Pseudotumor cerebri
• Sleep disorders
• Operative risk
• Osteoarthrosis
• Thromboembolism
• Urinary incontinence

Other reports suggest improved quality of life and fertility among postsurgical patients. Although other outcomes are difficult to demonstrate and are awaiting clear documentation, these procedures may substantially reduce macrovascular complications (eg, myocardial infarction), stroke, amputations, obesity-related malignancies, and a predisposition to infection, hernias, and varicose veins.

Patients in the Swedish Obese Subjects study who underwent bariatric surgery had reduced incidences of cardiovascular death and reduced occurrence of cardiovascular events, myocardial infarction, and stroke.^[82]

Although most bariatric procedures were initially developed in the setting of laparotomies, they now are increasingly performed laparoscopically, with reduced postoperative morbidity. The laparoscopic approach to bariatric surgery is particularly well developed in Europe.

Among the standard bariatric procedures are the following:

• Horizontal gastroplasty
• Roux-en-Y gastric bypass
• Biliopancreatic bypass
• Silicone gastric banding
• Adjustable gastric banding
• Jejunoileal bypass procedures
• Biliopancreatic bypass with duodenal-switch procedures

Although available data on the effectiveness of all of these procedures are still relatively scant, anecdotal reports on individual patients and a few reports on the most commonly performed procedures (gastric restriction and gastric bypass procedures) lend veracity to the long-term effectiveness of bariatric surgery.

Vertical-band gastroplasty

Ashley and colleagues, in an evaluation of 114 patients who underwent vertical-band gastroplasty,^[83] found that about 60% of them lost more than 50% of their excess body weight over 1 year. No patient lost less than 25%, and, within a year of the surgery, mean BMI had decreased from 44.8 to 32.5 kg/m².

Gastric bypass

Flickinger and associates, in an examination of 210 patients who received a Roux-en-Y gastric bypass,^[84] recorded a mean weight loss of 51 kg in 18 months, which was then maintained over 36 months of follow-up. Only 4% of the patients required a repeat operation.

Sugerman and colleagues reported that, among patients undergoing gastric bypass, two thirds of their excess body weight was lost over 2 years, 60% of the excess body-weight loss was maintained, and more than 50% of excess body-weight loss was maintained at 9 years’ follow-up.^[5]

Roux-en-Y and other gastric-bypass procedures generally result in more weight loss than do gastric-restriction procedures. When 329 patients receiving vertical gastroplasty procedures were compared with 623 persons undergoing Roux-en-Y gastric bypass, weight loss was maintained in 47% and 62% of patients, respectively, over 5-9 years of follow-up.^[5]

According to a study by Plecka et al, in patients who are morbidly obese, gastric bypass (but not restrictive surgery) apparently reduces the risk levels for the development of type 2 diabetes and myocardial infarction to those for the general population, but the mortality risk in these patients nonetheless remains higher than that of the general population.^[85]

A Swedish study compared gastric bypass with duodenal switch and determined that duodenal switch surgery was associated with greater weight loss and greater reductions of total and LDL-C levels but was also associated with increased adverse effects.^[86]

A study by Salehi et al found that although exaggerated glucagonlike peptide 1 (GLP-1) stimulated insulin response is observed in patients who undergo gastric bypass, it does not differentiate those with recurrent hypoglycemia from those without.^[87]

A systematic review and meta-analysis by Vilsbøll et al found that treatment with GLP-1 receptor agonists results in weight loss among overweight or obese patients with or without type 2 diabetes.^[88]

Gastric pacing

Emerging data suggest that gastric pacing achieved by using implantable electrodes may have significant weight-loss effects. This outcome was initially discovered with the use of gastric pacemaker devices for gastroparesis in patients with diabetes.

Cigaina reported that 10 patients in whom a pacing device was laparoscopically implanted showed a mean excess weight loss of about 25% at 3-year follow-up.^[89] Similar findings were reported in several European studies with a total cohort of about 50 patients. (See the image below.)

Additional procedures

Other adjunctive procedures that may be performed but that have an unclear utility include visceral fat removal, omentectomy, subcutaneous fat panniculectomy, and large-volume subcutaneous fat liposuction. Klein and colleagues indicated that liposuction in itself has no utility in improving cardiac risk factors among subjects with obesity.^[90]

Previous procedures, such as jaw wiring and insertion of a gastric balloon or a gastric wrap, are no longer popular because of their poor results compared with those of newer procedures and because of their high complication rates.

Vagotomy has also declined in popularity; although on its own vagotomy is associated with some weight loss, the weight is typically regained within a few years. A few reports suggest that when vagotomy is performed with gastric bypass, it increases weight loss by as much as 20%, but this finding has not been consistently replicable.

Surgical complications

Major procedure-specific postoperative complications to watch for include the following:

• Wound dehiscence
• Stomal strictures
• Erosions or ulcers
• Postprocedure diarrhea
• Malabsorption
• Dumping syndrome
• Anastomotic leaks with a potential for mediastinitis or peritonitis

In addition, gastric-specific operations can be associated with persistent vomiting, metabolic alkalosis, thiamine deficiency, and malabsorption of iron and vitamin B-12. These operations are more commonly associated with weight-loss failure and inadvertent splenectomy than are other methods.

Prevalences for adverse events are approximately 70% for dumping, 50% for dairy intolerance, 40% for constipation and headaches, 15% for depression, and 33% for hair loss. Vitamin B-12 deficiency was found in 25% of patients; incisional hernias, anemia, diarrhea, or abdominal pain each occurred in 15% of patients, while arrhythmias or single or multiple vitamin deficiencies not involving vitamin B-12 were each found in 10% of patients.

The mortality rate associated with standard bariatric surgical procedures in an experienced center should not exceed 1.5-2%. The surgical mortality rate is less than 0.5% at centers specializing in bariatric surgery. Mortality rates exceeding this rate suggest a risk-to-benefit ratio that probably is unacceptable.

Patients who receive bypass procedures are particularly prone to micronutrient deficiency states, especially of calcium, vitamin B-12, folate, and iron.

Among the major specific complications associated with malabsorptive operations are uncontrolled diarrhea, steatorrhea, malabsorption of fat-soluble vitamins, potassium and/or magnesium deficiency, blind-loop syndrome (which includes enteritis, arthropathy, and liver cirrhosis), gallstone development, urolithiasis, and metabolic encephalopathy.

If failure is defined as an inability to ameliorate comorbidities or prevent recurrence of such comorbidities, gastric bypass appears to have a failure rate of approximately 20%. Failure rates based on weight loss are controversial. The overall failure rates for malabsorptive procedures are relatively low, although the need for reversal of the surgery because of resulting adverse effects appears to be relatively high.

Despite the morbidity and mortality risk associated with bariatric surgery, the few reports on the follow-up of patients undergoing these procedures suggest overall improvement in quality of life. Even more convincing than this finding is that most subjects who undergo these procedures, irrespective of their postoperative complications and difficulties, indicate that they would undergo the procedures again if necessary.

Although weight-management programs may be based in an outpatient or inpatient setting, no rigorous evidence suggests that inpatient programs are necessarily superior to outpatient programs of similar structure and content.

Inpatient programs may offer the convenience of easy access to patients and ease of monitoring, but they are expensive to run, difficult to reimburse, and generally considerably disrupt the patients' regular routine. In addition, they offer little guarantee of sustained effect.

The major role for inpatient evaluations is in the immediate postoperative period after antiobesity surgery and in the management of major complications, such as clinically significant respiratory or cardiac compromise.

Because of the sheer prevalence of obesity and the anticipated worsening of the pandemic in the next few decades, prevention is by far the most desirable means to curb the medical and economic consequences of this condition. However, few trials have addressed this issue, and those performed thus far have had mixed results.^[55]

Results of some public health education initiatives in Singapore and parts of China that are only now being evaluated suggest, as hoped, that such programs have the potential for reducing the incidence and prevalence of obesity and the major comorbidities of obesity, such as type 2 diabetes and hypertension.

Until recombinant deoxyribonucleic acid (DNA) methods are developed enough to enable the alteration of genes that predispose individuals to obesity, the only options available are to develop a massive public health education program aimed at adults and children as a means of changing their eating, activity, and behavioral habits.

Given the global proportions of obesity, a concerted approach is needed to address the problem and should involve cooperative efforts among public health authorities, caterers, the fast food industry, and organizers of sports and outdoor games.

The following consultations are recommended in the treatment of obesity:

• Psychiatrist - Consultation with a psychiatrist is vital for identifying persons with psychiatric disorders and personality disorders, such as depression, mania, and obsessive disorders, that may be worsened by attempts at weight loss if not adequately treated and controlled
• Dietitians
• Exercise and physical therapists
• Behavioral scientists and/or psychologists
• Bariatric surgeon - In appropriate setting

As with the management of other chronic medical conditions that are not presently curable (eg, diabetes mellitus, hypertension, bronchial asthma), long-term success in the management of obesity is contingent on long-standing follow-up with the program.

Visits may not need to occur as frequently during follow-up as during the initial weight-loss phase, but they are paramount if the lessons learned regarding diet, exercise habits, and behavioral patterns are to be maintained.

Experience from the lifestyle intervention group of subjects in the Diabetes Prevention Program and the ongoing Diabetes Prevention Program Observation study have borne out the importance of regular follow-up.