Obesity is epidemic in the United States and other industrialized nations.¹ Currently, obesity is defined as a body mass index (BMI = weight in kilograms divided by height in meters squared) of 30 kg per m² or more.¹ There are three classes of severity: Class I (BMI of 30.0 to 34.9 kg per m²), Class II (BMI of 35.0 to 39.9 kg per m²) and Class III (BMI of equal to or greater than 40.0 kg per m²).¹ The age-adjusted prevalence rates of Class I, II and III obesity in American adults are estimated to be 14.4, 5.2 and 2.9 percent, respectively.¹ These estimates represent a substantial increase in the prevalence of all three obesity classes over the past decade.

Obese persons have a greater mortality risk, compared with nonobese persons.^1,2 In particular, obesity increases the risk of cardiovascular disease-related mortality one- to twofold.^1,3 Results of one study found that a BMI greater than 35 was associated with a sevenfold increase in mortality risk in coronary patients.⁴ Obesity is also associated with increased risk of multiple comorbid medical conditions, including hypertension, dyslipidemia, coronary heart disease, type 2 diabetes mellitus (formerly called non–insulin-dependent diabetes mellitus), gallbladder disease, sleep apnea, osteoarthritis and various forms of cancer.^1,4

One study found that obese persons (BMI of 30 or greater) are substantially more likely to have a comorbid medical condition, compared with persons who have BMIs in the healthy range (19.0 to 24.9 kg per m²).⁵ In this study, obese subjects were 1.7 times more likely to have heart disease, twice as likely to have hypertension and three times as likely to have diabetes, compared with persons in the healthy BMI range. The American Heart Association (AHA), in its call to action on obesity and heart disease, reclassified obesity as a major, modifiable risk factor for coronary heart disease.⁶

Successful Management of Obesity

Successful management of the obese patient involves multiple treatment strategies, most focusing on modification of the patient's lifestyle (e.g., diet and physical activity habits). Behavior modification, although not an intervention itself, is a systematic method for modifying eating, exercise or other behaviors that may contribute to or maintain obesity.⁷ Behavior modification techniques include self-monitoring, stimulus control, cognitive restructuring, stress management and social support.

SELF-MONITORING

Self-monitoring is the systematic observation and recording of target behaviors. Self-monitoring tools include the following: food diaries to record total caloric intake, total fat grams consumed, food groups used, and conditions or situations when overeating is common; physical activity logs to record frequency, duration and intensity of exercise; and weight scales or body composition measures to record changes in weight, body fat or lean body mass. Although patients are not always accurate in reporting their diet and exercise behaviors,⁸ the primary purpose of self-monitoring is for patients to become more aware of their behaviors and the factors that influence their behaviors in ways that are beneficial or detrimental to their weight management efforts. Research has consistently demonstrated that self-monitoring is associated with improved treatment outcomes, and patients report that it is one of the most helpful tools in obesity management.^9–11

Current guidelines from the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH) suggest that persons who desire to lose weight should reduce their caloric intake by 500 to 1,000 kcal per day, which will produce a weight loss of 0.45 to 0.90 kg (1 to 2 lb) per week.¹ According to the NHLBI guidelines,¹ women may choose a diet of 1,000 to 1,200 kcal per day and men may choose a diet of 1,200 to 1,500 kcal per day.

STIMULUS CONTROL

Stimulus control involves identifying and modifying the environmental cues that are associated with a patient's overeating and inactivity. By changing their individual environments, patients may be more successful in sustaining their weight management behaviors.¹² Controlling cues associated with overeating or a sedentary lifestyle can be helpful for long-term maintenance because exposure to these cues may precipitate relapse.¹² Suggestions for ways patients can implement this strategy include: eating only at the kitchen table without watching television; keeping no snack foods in the house; and laying out exercise clothes the night before as a reminder to walk or jog in the morning. Patients and their physicians should work together to develop practical, individualized stimulus control strategies that will fit the patient's lifestyle.

COGNITIVE RESTRUCTURING

Cognitive restructuring increases patient awareness of their perceptions of themselves and their weight. In addition, patients learn to actively change internal dialogue that undermines their weight management efforts. Cognitive restructuring is important because many obese patients have poor self-esteem and a distorted body image. Many are unrealistic about how much weight they can lose and the benefits that weight loss can have on their life. One obesity treatment study found that patients had weight loss expectations that were substantially greater than what was realistically attainable.¹³ Although most patients in this study lost about 10 percent of their initial weight during treatment,¹ this “modest” amount of weight loss was disappointing to the patients.¹³

Stress Management

Because stress is a primary predictor of relapse and overeating,¹¹ teaching patients various methods for reducing stress and tension is crucial. Tension reduction techniques (e.g., diaphragmatic breathing, progressive muscle relaxation and meditation) are designed to reduce tension and associated sympathetic nervous system arousal, thereby providing a distraction from stressful events. These strategies are highly effective for numerous health-related problems, including obesity.¹⁴

SOCIAL SUPPORT

Persons with higher levels of social support tend to have more success achieving and maintaining weight loss.¹¹ Social support can come from inclusion of the family in the obesity treatment program, participation in community-based programs or involvement in outside social activities (e.g., university or community education courses, health clubs and church-related activities). These groups or programs do not need to be oriented toward weight management. Peer support can be particularly useful in helping patients become more self-accepting, develop new norms for interpersonal relationships and manage stressful work- or family-related situations.^11,12

EFFECTIVENESS OF BEHAVIORAL STRATEGIES

Obesity interventions that incorporate these behavioral strategies are generally effective in producing gradual and moderate weight loss. Numerous studies over the past two decades show that the average weight loss is 0.45 kg (1 lb) per week and more than 8 kg (17.6 lb) over the total treatment period. Attrition rates are generally low (less than 18 percent), and the use of multiple behavioral strategies appears to be associated with greater weight loss.^1,15 Behavior modification interventions last about 18 weeks and usually include multiple treatment strategies. Patients are able to maintain, on average, about two thirds of their initial weight loss nine to 10 months after treatment termination.^1,15 Studies consistently show that behavior modification strategies, extended treatment and physical activity are excellent predictors of weight loss during treatment.^11,16

The Importance of Physical Activity in Weight Maintenance

Regular physical activity is associated with reductions in many medical comorbidities associated with obesity.^1,17 Physical activity is an important predictor of weight maintenance,^1,17 and the results of at least one study suggest that being physically active, even if the patient is obese, can substantially reduce one's risk for all-cause mortality.¹⁸ This study found that moderately and highly fit men, irrespective of their BMI, experienced significantly lower age-adjusted risk for all-cause mortality, compared with sedentary or low-fit men.¹⁸ The finding suggests the possibility of "healthy" obesity (persons who are obese but physically fit) and highlights the importance of increasing physical activity regardless of weight changes.

The American College of Sports Medicine recommends specific guidelines for exercise-induced weight loss.¹⁹ The exercise program should promote an expenditure of 300 to 500 kcal per session and 1,000 to 2,000 kcal per week for adults. However, this goal may not be realistic for the severely obese person. Thus, according to NHLBI guidelines,¹ obese patients should start with moderate levels of physical activity (e.g., brisk walking) for 30 to 45 minutes, three to five days per week (an expenditure of about 150 to 225 kcal per session), working up to exercise sessions on most, and preferably all, days of the week.

The Role of Pharmacotherapy

Although behavior modification strategies are helpful for most obese patients, they do not guarantee long-term weight-loss maintenance. Without recurrent contact, most or all of the weight patients lose can be regained within three to five years.¹⁵ This limitation contributed to the active development of pharmacologic approaches to obesity. Current guidelines consider pharmacotherapy to be an adjunct to lifestyle modification programs and are targeted toward at-risk patients (patients with a BMI of 30 or greater, or a BMI of 27 or greater combined with medical comorbidities).^1,20 Several early studies^21,22 evaluated the effectiveness of drug treatment alone (using fenfluramine administered during brief physician visits), behavior therapy alone and drug treatment combined with behavior therapy. Behavior therapy alone and drug treatment combined with behavior therapy produced substantially greater weight loss at the end of the treatment period when compared with the wait-list control group or the patients receiving the drug alone.^21,22

Studies of obesity medications, usually in conjunction with dietary programs, demonstrate modest benefits compared with studies of behavior modification programs and placebo.¹ The effects of pharmacotherapy tend to maximize within six months, and weight loss is generally maintained for the duration of treatment. Currently available obesity medications are listed in Table 1.

Noradrenergic Drugs. One class of weight-loss medications is the noradrenergic drugs that affect weight loss by suppressing one's appetite. Some noradrenergic agents include: phentermine resin (Ionamin), mazindol (Sanorex), phenylpropanolamine (Dexatrim), phendimetrazine (Plegine) and diethylpropion (Tenuate). When combined with dietary programs, these drugs produced modest short-term net weight losses compared with dietary changes and placebo. The U.S. Food and Drug Administration (FDA) has not labeled any of these drugs for long-term treatment of obesity.

Orlistat. Orlistat (Xenical) is a lipase inhibitor²³ that has been approved by the FDA for long-term use. After 12 weeks of treatment with orlistat (360 mg per day), patients in a clinical study showed weight losses of up to 5 kg (11 lb), compared with 2-to 3-kg losses (4.4 to 6.6 lb) among patients in the placebo group.^23,24 Weight losses appear to be dosage-dependent, with lower dosages producing smaller weight losses, and some patients report mild and transient gastrointestinal side effects. The results of a 52-week randomized, double-blind, clinical trial demonstrated sustained weight loss in the treatment group (120 mg three times daily), averaging a weight loss of 3 kg (6.6 lb) more than the placebo group.²⁵

A more recent study²⁶ found that patients treated with orlistat over a two-year period experienced significant improvements in several health parameters. For example, during the first year, patients receiving orlistat lost more weight than patients receiving a placebo. Patients treated with orlistat (120 mg, three times per day) during years 1 and 2 regained less weight during year 2 than patients treated with orlistat (60 mg three times per day) or placebo. Treatment with orlistat (120 mg three times per day) was also associated with improvements in fasting low-density lipoprotein (LDL) cholesterol levels and insulin levels.²⁶

In a one-year randomized, double-blind study of obese patients with type 2 diabetes, patients receiving orlistat lost more weight than patients receiving a placebo.²⁷ In addition, patients treated with orlistat plus a modification of their diet showed reductions in dosage of sulfonylurea medications and significant improvements in hemoglobin A_1c (HbA1_c) fasting plasma glucose levels, and lipid parameters (total cholesterol levels, LDL cholesterol levels, triglyceride [TG] levels, apolipoprotein B levels, and the LDL-to-high-density–lipoprotein [HDL] ratio) when compared with placebo plus diet modifications.²⁷

Sibutramine. Sibutramine (Meridia), which has been approved by the FDA for long-term treatment of obesity, is a specific reuptake inhibitor of norepinephrine and serotonin, thus having satiating and potential thermogenic effects.^28,29 Preclinical studies in animal models showed that sibutramine and its metabolites reduced food intake and that animals eating a high-fat diet were more sensitive to sibutramine.²⁸ Several clinical studies of 12 to 52 weeks' duration showed weight losses of 4.7 to 7.6 kg (10.3 to 16.7 lb) in patients receiving sibutramine.^30,31 Weight losses were dosage-dependent and tended to plateau by the 24th week. Efficacy of sibutramine at one year has also been established. Patients taking 5-, 10-, and 15-mg daily dosages experienced dosage-related weight loss for up to 12 weeks, and all dosages were well-tolerated.³¹

A 52-week trial³⁰ of sibutramine found that patients receiving the 10 mg per day dosage, the 15 mg per day dosage, and a placebo lost 4.8 kg (10.6 lb), 6.1 kg (13.4 lb), and 1.8 kg (4.0 lb), respectively. The percentage of patients who lost at least 5 percent of their initial body weight over a 21-month period was 56 percent in the patients taking 10 mg per day, 65 percent in the patients taking 15 mg per day, and only 29 percent in the subjects receiving placebo. Thirty percent of the subjects taking 10 mg per day and 39 percent of subjects in the group receiving 15 mg per day reached the 10 percent loss of initial body weight criteria while only 8 percent of subjects in the placebo group reached that level of weight loss.³⁰ Treatment with sibutramine also can improve many obesity-related comorbidities.^28,29

A one-year study of patients using 10 or 15 mg per day of sibutramine found significant reductions in waist-to-hip ratio compared with patients receiving placebo.³⁰ Sibutramine-induced weight losses have also been found to produce favorable reductions in plasma TG, total cholesterol, LDL and HbA_1c levels.³⁰ In a 12-week study,³² 91 patients with type 2 diabetes were randomized to receive 15 mg of sibutramine or placebo. Patients who received sibutramine showed moderate but significant weight loss as well as improvements in HbA_1c levels, compared with patients in the placebo group.

All drug therapies can have adverse effects that may include depression, neurotoxicity, valvular heart disease, primary pulmonary hypertension, and the potential for abuse of or the development of tolerance to the drug being taken.^33,34 Other side effects can include diarrhea, polyuria, dry mouth, sleep disturbance, nervousness, sexual dysfunction and increased blood pressure, but these effects are generally mild to moderate and tend to ameliorate with continued treatment.¹ Reviews of pharmacotherapy for weight management are available.^33–36

Systemic side effects of orlistat are minimal because it acts on gastrointestinal lipases and is minimally absorbed.²⁶ Adverse events tend to be similar in orlistat- and placebo-treated groups^26,27 with the exception of gastrointestinal events. Gastrointestinal symptoms typically include flatus with discharge, oily spotting, fecal urgency, fatty/oily stool, oily evacuation, fecal incontinence and increased defecation.²⁶ These symptoms are predictable, tend to diminish over time, and tend to be more pronounced in patients who have difficulty maintaining a moderate dietary fat intake. Absorption of fat-soluble vitamins (A, D and E) and carotenoids may be affected, so the use of orlistat should be supplemented with a multivitamin.

Side effects of sibutramine include mean increases of 1 to 3 mm Hg in systolic blood pressure (SBP) and diastolic blood pressure (DBP) and an increase in pulse rate. Increases in blood pressure may be partially mitigated by sibutramine-related weight losses.³⁰ In controlled safety trials, 0.4 percent of patients treated with sibutramine and 0.4 percent of patients who received a placebo discontinued use because of hypertension (SBP greater than 160 mm Hg; DBP greater than 95 mm Hg), while 0.4 percent of patients treated with sibutramine and 0.1 percent of patients who received a placebo discontinued use because of tachycardia (pulse rate greater than 100 beats per minute). In placebo-controlled trials, the most common side effects were dry mouth, anorexia, insomnia and constipation. No cases of primary pulmonary hypertension or valvular heart disease have been reported to be associated with sibutramine.^30,31

Assessing Treatment Outcome

Although the primary goal of obesity treatment programs is weight loss, there are now broader definitions of what constitutes successful treatment. More emphasis is being placed on outcomes such as improvements in metabolic profiles and comorbid medical conditions (e.g., hypercholesterolemia, diabetes); physical activity; self-esteem; body image; self-efficacy; mood and psychologic status; quality of life; and activities of daily living or functional status.¹³ Methods for measuring these outcomes must be incorporated in a comprehensive obesity management program.

Summary

Obesity is a chronic disease with no known cure. It requires long-term management similar to that of diabetes and hypertension.⁵ The use of long-term management strategies for chronic diseases is not perceived as treatment failure. Nor is treatment considered ineffective when a patient has difficulty adhering to the interventions. Rather, we acknowledge that many health care problems require long-term management and a focus on improving adherence to treatment. Obesity is best thought of and treated as a chronic disease requiring continuous care.

Given this chronic disease model of obesity, treatment should no longer require large weight losses. Modest, sustained weight losses (5 to 10 percent of initial body weight) have been shown to positively modify many comorbid disease risk factors.¹ Patients and physicians should focus on making lifestyle changes in small steps that lead to moderate and lasting weight losses. Because of the inherent difficulties in treating obesity, physicians should also attempt to develop continuous care programs emphasizing lifestyle modifications, such as enduring changes in dietary and activity habits. Patients using behavior modification strategies to make these changes are more likely to succeed in long-term weight maintenance.^11,16 Table 2 provides a summary of basic obesity treatment recommendations.

Finally, it is crucial that physicians become more involved in the prevention of obesity. Currently, 13.7 and 11.5 percent of children and adolescents, respectively, are obese.¹ Because childhood obesity is associated with adult obesity, physicians should intervene early with overweight children and their parents. The AHA, in its call to action on obesity,¹² states that the development of obesity prevention in children is key to decreasing the current obesity epidemic. This critical health issue needs to be seriously addressed, or the long-term social and economic toll on the nation will be incalculable.