Medical Care

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 (1) a preinclusion screening phase; (2) a definitive weight-loss program; and (3) a maintenance phase, which can conceivably last for the rest of the subject's life but which must last for at least 2 years after the weight-loss program is completed.

• Weight loss as medical treatment

  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. In a study of approximately 200 obese black women, the Obesity Reduction Black Intervention Trial (ORBIT) investigated whether greater weight loss could be achieved with a culturally adapted weight-loss program than with a more general health program.

  The women 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, psychologists or psychiatrist, physical and exercise therapists, dietitians, and other subspecialists, depending on the comorbidities of the individual patient.

 

• Results of weight-loss management

Results of most weight loss management programs are dismal. On average, participants in the best weight-loss programs lose approximately 10% of their body weight, but people generally regain two thirds of the weight lost within a year, and they regain almost all of it within 5 years.

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.

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.

• Childhood obesity

  For childhood obesity, the goal is to reduce the rate of weight gain to fit the profile expected based on normal growth curves. The intent here is not to cause weight loss.

  The basic principles of management include (1) modifying diet, (2) increasing appropriate physical activity and exercise, (3) reducing time spent in sedentary activities (eg, watching TV), and (4) modifying behavior.

  Added to these principles is medication therapy. However, such therapy is still rudimentary in the management of pediatric obesity, and 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.

• Dietary programs

Starvation is a caloric intake of less than 200 kcal/d 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 are the fact that energy expenditure is related to body weight; about 22 kcal/kg of energy 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 is achieving sustained weight loss. The estimated reduction in energy expenditure is 100 kcal per decade after the age of 30 years.

Very low-calorie diets (VLCDs) are best used in an established, comprehensive program. VLCDs involve reducing caloric intake to 800 kcal/d or less. When used in optimal settings, they can achieve 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 though they are associated with improved blood pressure and glycemic control, they cannot be sustained 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 subjects quickly regain all the weight they lose 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 subjects with very severe or morbid obesity and associated comorbidities (BMI >50).

Conventional diets can be broadly subclassified as (1) balanced, low-calorie diets (or reduced portion sizes), (2) low-fat diets, (3) low-carbohydrate diets, (4) midlevel diets (eg, Zone diet in which the 3 major macronutrients [fat, carbohydrate, protein] are eaten in similar proportions of 30-40%), and (5) fad diets.

Balanced LCDs or reduced portion sizes 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 subject, 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 u3 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 800-1200 kcal/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 intake of protein with high biologic value of >1 g/kg is vital to preserve 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 involve diets with a caloric intake greater than 1200 kcal/d. The aim with this type of diet is to reduce the caloric intake by 500-1000 kcal/d from the patient's current dietary intake. The suggested composition for the best-validated dietary programs are protein intake of 0.8-1.5 g/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 >50 g/d, and water intake of >1 L. Ensure that the dietary plan provides adequate micronutrients and macronutrients based on RDAs.

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 <50 g, force sodium diuresis, which causes 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 the equivalent caloric intake as carbohydrate; however, no physiologic data support this premise.

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

In 2 randomized trials weight loss with Atkins-type diets were 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, though lipids did not appear to be deleteriously affected, follow-up was only about 1 year, and noncompliance rates in the Atkins-type group was close to 50%.

The South Beach diet is another low-carbohydrate diet. This program is more liberal than the Atkins diet in its carbohydrate allowance; therefore, compliance rates are enhanced. The South Beach diet distinguishes between what it 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.

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

Dansinger and colleagues (2005) compared the Zone, Ornish, and Atkins diets and a typical balanced, calorie-restricted (Weight Watchers) diet.17 The Ornish diet, very-low-fat diet, and the Atkins diets 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 specific dietary composition.

For subjects who decide to use a low-carbohydrate diet, they 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, or mutton).

• Exercise programs

  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.

  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 build muscle mass, increasing metabolic activity of the whole-body mass. Exercise also helps 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.

• Behavioral changes

  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 both a highly motivated subject and a dedicated counselor who is willing to maintain long-term follow-up.

• Medications

  Not many medications are available for the treatment of obesity, and those that are available have minimal long-term effectiveness.

  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 are 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).

  D-fenfluramine was withdrawn because of problems with cardiac valvulopathies and primary pulmonary hypertension (PPH).

  Fluoxetine: This drug is not approved for use in achieving weight loss, but it has been known to cause minimal weight loss as an adverse effect, which is sometimes exploited.

  Fenfluramine: Although effectively used in combination with phentermine, it was withdrawn in 1997 (along with D-fenfluramine) because of the potential for adverse cardiac, valvular, and pulmonary hypertensive effects.

  Phentermine: The combination of fenfluramine and phentermine was used in some long-term trials with fair results.

  Diethylpropion: This drug is only for short-term use (25 mg 3 times/d [tid]).

  Phendimetrazine: This drug is only for short-term use (30 mg/d).

  Benzphetamine: This drug is only for short-term use (20-50 mg tid).

  Mazindol: This drug was withdrawn from US market in 2001. It was only for short-term use (1 mg tid).

  Phenylpropanolamine (recalled from US market): This drug is only for short-term use (25 mg tid). Phenylpropanolamine is an alpha-adrenoreceptor agonist. Some reports have 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 is excluded.

  Methylphenidate: This drug is not approved by the FDA for obesity management, though several anecdotal reports describe its use with variable success.

  Sibutramine (Meridia): This is a centrally acting appetite suppressant that inhibits reuptake of noradrenalin, serotonin, and dopamine.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.

  Orlistat (Xenical): This agent blocks the action of pancreatic lipase, reducing triglyceride digestion and, thus, absorption.Two major clinical trials showed sustained weight loss of 9-10% over 2 years.

  Ephedrine and caffeine: These 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.

  Serotonin selective receptor uptake inhibitors (SSRIs): Although not FDA approved for this purpose, several 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.

  Bupropion and venlafaxine: Other preliminary reports suggest the possible utility of some medications in the management of weight loss. Bupropion, which is licensed for use as both an antidepressant and in smoking cessation, is associated with minimal-to-moderate weight loss.Preliminary reports suggesting similar findings with venlafaxine.

  Topiramate: Topiramate, licensed as an adjunctive antiepileptic agent, was associated with profound weight loss of as much as 15-18% of the baseline weight. The amount of weight lost 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/day in divided doses). Doses >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.

  Dronabinol (Marinol) and rimonabant: Importance of the central cannabinoid system in the understanding and management of feeding disorders has increased.

  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 AIDS and other wasting syndromes. CB1 antagonists showed great potential for weight management in several human trials.

  Rimonabant, the most-developed CB1 antagonist, caused mean weight loss of 3-6 kg over 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. Rimonabant may obtain FDA approval as an adjunct for weight loss in the next 2-3 years based on the accumulating data from phase 3 trials of human obesity.

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

  Agents at various stages of investigation as potential pharmacotherapeutic adjuncts in obesity are described below.

  Metformin: This drug 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.

  The antiepileptic Zonisamide: Gadde and colleagues (2003) reported that randomized use of this drug in a cohort of 60 obese subjects was associated with a weight loss of about 6% of baseline weight with few adverse effects.

  Octreotide: Lustig and colleagues (2003) reported the potential utility of octreotide in ameliorating the distinct subclass of hypothalamic obesity.

  Glucagon-like peptide (GLP)-1 analogs: The first of these was exenatide. Although this drug is not FDA approved for obesity management, it was associated with modest weight loss in subjects with type 2 diabetes.

  Peptide YY (3-36): This agent is being developed as a nasal inhaler. Preliminary, ongoing phase 1 and 2 trials yielded encouraging results.

  Amylin: This is the synthetic version pramlintide and does not have an FDA indication for obesity management. 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 other agents that initially showed promise were later demonstrated to be poor prospects in rigorous randomized intervention trials. These include Guar gum, Axokine (or ciliary neurotrophic factor, the use of which was associated with development of autoantibodies and marked reduction in anorexiant potency in about 30% of subjects), leptin (except in the rare subclass of leptin-deficient obesity), St John's Wort, Psyllium, conjugated linoleic acid, chromium, and ginseng, among others.

• 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.

• Public policy and obesity management

  Although management of obesity in the individual subject is important, realizing that obesity is a public-health problem is vital. Successful management of the obesity pandemic requires public health professionals and administrators to make tough policy decisions.

  The multibillion-dollar food industry and the link between this industry and the consumer (including retailers and caterers) must be included in this public-health effort. The high-density foods, snacks, and drinks that are so common in the developed world and that now are infiltrating developing countries must be recognized as major factors in this pandemic.

  Large-scale public-health education aimed at all age groups must be implemented with the same fervor and zeal that characterized past advertisements for tobacco. Such public-health initiatives must be accompanied by an equally spirited effort to educate the public and to encourage regular participation in exercise and outdoor recreational activities among individuals of all ages.

• Fat substitutes

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

  Olestra (Olean) has been approved for use as a dietary supplement and additive in various fast 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 making it too large for digestive enzymes of the gut to hydrolyze it. In many trials, olestra had fairly good tolerability, though 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 the concern for 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 in triglyceride or HDL-C values.

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

Surgical Care

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 ameliorates 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 these procedures must be addressed along the same stringent lines as those discussed above for potential patients for medical weight-management programs (see Medical Care).
• The presence of comorbidities is not a contraindication to these 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.
• Among the comorbidities reported to be ameliorated and/or resolved by bariatric surgery are type 2 diabetes mellitus, hypertension, heart failure, peripheral edema, respiratory insufficiency, asthma, dyslipidemia, esophagitis, pseudotumor cerebri, sleep disorders, operative risk, osteoarthrosis, thromboembolism, and 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.
• 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 (1) horizontal gastroplasty, (2) roux-en-Y gastric bypass, (3) biliopancreatic bypass, (4) silicone gastric banding, (5) adjustable gastric banding, (6) jejunoileal bypass procedures, and (7) biliopancreatic bypass with duodenal-switch procedures.
  • Although available data on the effectiveness of all these procedures are still relatively scant, anecdotal reports of individual patients and a few reports of the most commonly performed procedures (gastric restriction and gastric bypass procedures) lend veracity to the long-term effectiveness of bariatric surgery.
  • Ashley and colleagues (1993) examined 114 subjects who underwent vertical-band gastroplasty.About 60% 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.
  • Flickinger and associates (1984) examined 210 subjects who received roux-en-y gastric bypass.The mean weight loss was 51 kg in 18 months, which was then maintained over 36 months of follow-up. Only 4% required a repeat operation.
  • Sugerman and colleagues (1992) 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 lost was maintained, and more than 50% of excess body weight lost was maintained at 9-years follow-up.
  • Roux-en-y and other gastric-bypass procedures generally result in more weight loss than gastric-restriction procedures. When 329 subjects receiving vertical gastroplasty procedures were compared with 623 subjects undergoing roux-en-Y gastric bypass, weight loss was maintained in 47% and 62%, respectively, over 5-9 years of follow-up.
• 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 (2004) indicated that liposuction in itself has no utility in improving cardiac risk factor among subjects with obesity.
• Previous procedures, such as jaw wiring, insertions of gastric balloon, and insertions of gastric wrap are no longer popular because of their poor results compared with those newer procedures and because of their high complication rates.
• Vagotomy has declined in popularity. On its own, vagotomy is associated with some weight loss, but 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.
• Among the major procedure-specific postoperative complications to watch for are wound dehiscence, stomal strictures, erosions or ulcers, postprocedure diarrhea, malabsorption, dumping syndrome, and 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 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, in 15% each; and arrhythmias or single or multiple vitamin deficiencies not involving vitamin B-12, in 10% each.
  • 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.
• Subjects 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, though 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 subjects 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.
• Emerging data suggest that gastric pacing achieved by using implantable electrodes may have substantial significant weight-loss effects. This outcome was initially discovered with the use of gastric pacemaker–devices for gastroparesis in subjects with diabetes.
  • Transneuronix conducted the first set of trials of a device, and findings were largely reported in abstracts. Medtronic, an established company in the arena of medical devices that developed continuous, subcutaneous insulin-pump technology, acquired Transneuronix, as seen in the image below. Recruitment is ongoing for the Appetite Suppression Induced by Stimulation Trial (ASSIST) to evaluate this technology in patients with obesity and type 2 diabetes.
    
    Gastric electrical-stimulation device
    
    
    
    
  • .Cigaina (2002) reported that 10 patients in whom the pacing device was laparoscopically implanted showed a mean excess weight loss of about 25% at 3-year follow-up.
  • Similar findings were replicated in several European studies with a total cohort of about 50 patients.

Consultations

• 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

Medication

Few medications are available for the management of obesity. The list of putative therapeutic agents being investigated has increased considerably with the explosion in our knowledge of the pathogenesis of obesity. Improved understanding of the neurocircuitry of the feeding-satiety cycle has provided many potential targets for designer therapeutic agents that are being developed (see image below).

Central nervous system neurocircuitry
for satiety and feeding cycles.

Most medications available for managing obesity are approved only for short-term use. Available literature indicates that their utility is severely limited when they are given in this fashion. Obesity is a chronic medical condition. As with similar chronic conditions (eg, diabetes, hypertension), after therapeutic agents are stopped, the relapse rate is high. The need for any pharmaceutical regimen to be combined with a sustained exercise, dietary adjustment, and a behavioral-change regimen to sustain weight loss further complicates the successful management of obesity.

The FDA approved 2 medications for the long-term management of obesity in adults. Of these, only orlistat is approved for use in adolescents, who represent the next wave of the obesity pandemic that is anticipated in the next few decades.

A Japanese study found evidence that beverages containing high amounts of catechin, a flavonoid found in green tea, may aid in preventing obesity.38 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.
Anorexiants

Anorexiants are administered to manage obesity. Indications included weight loss and maintenance of weight loss, in conjunction with a reduced calorie diet, specifically in patients who are obese with an initial BMI of 30 or 27 mg/m2  and other risk factors (eg, diabetes mellitus, dyslipidemia, hypertension).

Sibutramine (Meridia)

Inhibits central reuptake of neurotransmitters (eg, dopamine, norepinephrine, serotonin). Pharmacologic action of inhibiting serotonin reuptake may enhance satiety, while action inhibiting of norepinephrine reuptake raises metabolic rate. In Europe Sibutramine has been banned on January 10, 2010.

Dosing

Adult

10 mg PO qd; increase to 15 mg PO qd in 4 wk prn; dose-response effect at 5-30 mg qd; 5-mg dose reserved for patients who cannot tolerate 10-mg dose

Pediatric

<16 years: Not established
>16 years: Administer as in adults

Interactions

Ketoconazole, cimetidine, and erythromycin inhibit metabolism; increased risk of serotonin syndrome with MAOIs, SSRIs, sumatriptan, zolmitriptan, dihydroergotamine, dextromethorphan, meperidine, pentazocine, fentanyl, lithium, tryptophan, furazolidone, linezolid, and procarbazine; increased risk for cardiovascular complications with ephedrine, pseudoephedrine, and phenylpropanolamine (withdrawn from US market)

   
Contraindications

Documented hypersensitivity; during or within 2 wk of monoamine oxidase inhibitor (MAOI) administration; concomitant use of centrally acting appetite suppressants; anorexia nervosa; poorly controlled hypertension; coronary artery disease; congestive heart failure; cardiac arrhythmias; stroke

Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Before use, exclude organic causes of obesity (eg, untreated hypothyroidism); caution in closed-angle glaucoma (causes mydriasis); caution in seizure disorder (discontinue if seizures develop); precipitates or exacerbates gallstone formation; contributes to development of dental caries, periodontal disease, oral candidiasis, and discomfort; dose adjustment may be necessary in renal or hepatic disease; schedule C-IV; use controlled substance cautiously in patients with history of substance abuse

Note: Sibutramine blamed for increasing patients' chances of suffering a heart attack or stroke.

The European Medicines Agency (EMA) ordered doctors across the continent to stop prescribing sibutramine and told pharmacists not to dispense the drug, which is marketed in the UK as Reductil.
Dr June Raine, from the MHRA said: "Evidence suggests that there is an increased risk of non-fatal heart attacks and strokes with this medicine that outweigh the benefits of weight loss, which is modest and may not be sustained in the long term after stopping treatment."

Orlistat (Xenical)

GI lipase inhibitor that induces weight loss by inhibiting nutrient absorption. Effectiveness in producing weight loss does not depend on systemic absorption. May reduce absorption of some fat-soluble vitamins (A, D, E, K) and beta-carotene. Administer multivitamin supplement containing fat-soluble vitamins PO qd 2 h ac or 1 h pc.

Dosing

Adult

120 mg PO tid ac (meals containing fat); may take up to 1 h pc

Pediatric

60 mg PO tid ac initially; may uptitrate to 120 mg tid as tolerated, especially in overweight or obese adolescents with adult weight

Interactions

Decreases absorption of vitamin A, D, K, acitretin, calcifediol, calcitriol, dihydrotachysterol, doxercalciferol, ergocalciferol, isotretinoin, tretinoin, and beta-carotene; decreased vitamin K absorption may effect warfarin therapy; enhances effect of statin lipid-lowering agents; may decrease cyclosporin levels; may enhance hypoglycemic effect of sulfonylureas

   
Contraindications

Documented hypersensitivity; cholestasis; chronic malabsorption syndrome

   
Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions

Caution in organic causes of obesity (eg, hypothyroidism), rule out causes of obesity other than dietary intake before use; caution in calcium oxalate nephrolithiasis or hyperoxaluria (increased levels of urinary oxalate may occur); potential for abuse by certain patients, including those with anorexia nervosa or bulimia nervosa

Ephedrine (Pretz-D)

Sympathomimetic drug that directly and indirectly stimulates alpha- and beta-receptors. Not FDA approved for management of obesity. Recommended doses are for indications other than management of obesity.

Dosing
Adult

25-50 mg PO q3-4h prn
OTC products: 12.5-25 mg PO q4h; not to exceed 150 mg qd
Pediatric

<12 years: Not established; 2-3 mg/kg/d (100 mg/m2) PO divided into 4-6 doses qd has been administered to children >12 years

Interactions

Theophylline, atropine, thyroid hormones, MAOIs, furazolidone, linezolid, and procarbazine may increase toxicity; alpha-blockers and beta-blockers decrease vasopressor effects; cardiac glycosides and general anesthetics increase cardiac stimulation of ephedrine

   
Contraindications

Documented hypersensitivity; angle-closure glaucoma; cardiac arrhythmias

   
Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in elderly patients and in diabetes mellitus, hyperthyroidism, hypertension, cardiovascular disease, prostatic hypertrophy, cerebrovascular insufficiency, or history of mania or deviant personality disorders; respiratory insufficiency characterized by hypoxia, hypercapnia, or acidosis may reduce the effectiveness or increase the adverse effects associated with therapy (correct conditions before or during therapy)

Caffeine

Natural xanthine derivative that directly stimulates all levels of CNS, cardiovascular system, and voluntary muscles. Increases gastric acid secretion and renal blood flow. Has mild diuretic activity.

Dosing

Adult

Anhydrous caffeine: 100-200 mg PO q3-4h prn
Citrated caffeine: 65-325 mg (equivalent to 32-162 mg anhydrous caffeine) PO tid prn
Anhydrous caffeine extended-release (ER) capsules: 200-250 mg PO q3-4h prn; not to exceed 1000 mg/d

Pediatric

Not established

Interactions

Enhanced stimulant effect with amphetamines, ephedrine, methylphenidate, modafinil, nicotine, pemoline, pseudoephedrine, phenylpropanolamine, theophylline, and beta2-agonists; increased risk of stroke with phenylpropanolamine; decreased clearance/increased toxicity with ciprofloxacin, enoxacin, grepafloxacin, levofloxacin, and norfloxacin; metabolism enhanced by barbiturates, phenytoin, nicotine, and rifampin; metabolism inhibited by cimetidine, clarithromycin, erythromycin, ethinyl estradiol (hormonal oral contraceptives), fluvoxamine, ketoconazole, tacrine, terbinafine, zileuton, and grapefruit juice; decreases lithium serum concentrations; increased risk of cardiac arrhythmias and hypertension with MAOIs; antagonizes benzodiazepine sedative effects

   
Contraindications

Documented hypersensitivity; cardiac arrhythmias; recent myocardial infarction

   
Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions

May exacerbate peptic ulcer disease, insomnia, anxiety disorders, panic disorders, and CNS disorders; may destabilize blood glucose control in diabetes mellitus; hepatic disease may decrease clearance and increase toxicity; hyperthyroidism may increase stimulant effect

Bio-Slender

Bio-Slender is an orally administered anorexiant agent for the treatment of obesity. Its composition is  formulated from natural products Camellia sinensis, Taraxacum officinale, Garcinia cambogia 5-Hydroxytryptophan, Paullinia cupana, Panax Ginseng and Chitosan .

Dosing

Adult

Bio-Slender: 300 mg for formula containing natural ingredients, 2 capsules per day

Pediatric

14-16 years: 1 capsule per day 300mg
>16 years: Administer as in adults

Interactions

Selective Serotonin Reuptake Inhibitors (SSRIs) : (e.g. Fluoxetine, Fluvoxamine, Sertraline, Sibutramine)Selective serotonin reuptake inhibitors are used for depression, premenstrual dysphoric syndrome, bulimia nervosa, obsessive compulsive disorder, and weight loss. Bio-Slender contains 5-HTP which  is converted to serotonin, so medications that increase serotonin may increase the risk of developing a rare but serious condition called serotonin syndrome-symptoms include confusion, muscle rigidity, hot flashes, changes in blood pressure and heart rate, and coma.
Triptans: (e.g. Sumatriptan, Zolmitriptan, Rizatriptan, Naratriptan, Almotriptan, Eletriptan, Frovatriptan)  Triptan drugs are used to treat, but not prevent, migraines. These drug works by affecting serotonin receptors in the brain. If taken in combination with 5-HTP (a supplement that also affects serotonin levels), they may increase the risk of serotonin syndrome.
MAO inhibitor drugs :(e.g. Phenelzine,  Tranylcypromine) MAO inhibitors are used in the treatment of depression and panic disorder and in the prevention of headache. Although there have been no reported drug interactions with 5-HTP or with any other ingredient in Bio-Slender, MAO inhibitors may cause drowsiness, confusion, fever, agitation, seizures, elevated blood pressure, called serotonin syndrome.  No historic or clinically significant interaction has been observed or reported when patients concurrently taken Bio-Slender and MAOs but Caution should be used when prescribing Bio-Slender to patients who use MAO inhibitors.

   
Contraindications

Hypersensitivity to active components. Shouldn’t be taken if you are pregnant or nursing.

WARNINGS
No warnings are currently listed for Bio-Slender® due to the botanical nature of the principal ingredients used in the formulation.  Organic causes of obesity such as hypothyroidism should be excluded before prescribing Bio-Slender.  

Precautions

Pregnancy

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