Obesity

Obesity occurs when there is an imbalance between energy intake and energy expenditure over time, resulting in increased energy storage.

• The etiology of obesity is usually unknown, but it is likely multifactorial and related to varying contributions from genetic, environmental, and physiologic factors.
• Genetic factors appear to be the primary determinants of obesity in some individuals, whereas environmental factors are more important in others. Identification of the total number of contributing genes is an area of extensive research.
• Environmental factors include reduced physical activity or work, abundant food supply, relatively sedentary lifestyles, increased availability of high-fat foods, and cultural factors and religious beliefs.
• Medical conditions including Cushing disease and growth hormone deficiency or genetic syndromes such as Prader–Willi syndrome can be associated with weight gain.
• Medications associated with weight gain include insulin, corticosteroids, some antidepressants, antipsychotics, and several anticonvulsants.

Clinical Evaluation

Obesity is associated with serious health risks and increased mortality. Central obesity reflects high levels of intraabdominal or visceral fat that is associated with the development of hypertension, dyslipidemia, type 2 diabetes, and cardiovascular disease. Other obesity comorbidities are osteoarthritis and changes in the female reproductive system.

• Body mass index (BMI) and waist circumference (WC) are recognized, acceptable markers of excess body fat that independently predict disease risk.
• BMI is calculated as weight (kg) divided by the square of the height (m2).
• WC, the most practical method of characterizing central adiposity, is the narrowest circumference between the last rib and the top of the iliac crest.

Treatment

Goals of Treatment: Weight management goals may include losing a predefined amount of weight, decreasing the rate of weight gain, or maintaining a weight-neutral status, depending on the clinical situation.

General Approach

Successful obesity treatment plans incorporate reduced caloric intake, exercise, behavior modification with or without pharmacologic therapy, and/or surgery. Weight loss of 5% to 10% of initial weight is a reasonable goal for most obese patients. Measures of success not only include pounds lost but also improvement in comorbid conditions, including blood pressure, blood glucose, and lipids.

• Many diets exist to aid weight loss. Regardless of the program, energy consumption must be less than energy expenditure. A reasonable goal is loss of 0.5 to 1 kg per week with a diet balanced in fat, carbohydrate, and protein intake.
• Increased physical activity combined with reduced calorie intake and behavior modification can augment weight loss and improve obesity-related comorbidities and cardiovascular risk factors.
• The primary aim of behavior modification is to help patients choose lifestyles conducive to safe and sustained weight loss. Behavioral therapy is based on principles of human learning, which use stimulus control and reinforcement to substitute desirable behaviors for learned, undesirable habits.
• Bariatric surgery, which reduces the stomach volume or absorptive surface of the alimentary tract, remains the most effective intervention for obesity. Surgery should be reserved for those with BMI above 35 or 40 kg/m2 and significant comorbidities due to the morbidity and mortality associated with the surgical procedures

Pharmacologic Therapy

The debate regarding the role of pharmacotherapy remains heated, fueled by the need to treat a growing epidemic and by the fallout from the removal of several agents from the market because of adverse reactions.

• Long-term pharmacotherapy may have a role for patients who have no contraindications to approved drug therapy . The National Institutes of Health guidelines recommend consideration of pharmacotherapy in adults with BMI ≥30 kg/m2 and/or WC ≥40 in (102 cm) for men or 35 in (89 cm) for women, or BMI of 27 to 30 kg/m2 with at least two concurrent risk factors if 6 months of diet, exercise, and behavioral modification failed to achieve weight loss.
• Orlistat (180 or 360 mg in 3 divided doses/day) is a lipase inhibitor that induces weight loss by lowering dietary fat absorption; it also improves lipid profiles, glucose control, and other metabolic markers. Soft stools, abdominal pain or colic, flatulence, fecal urgency, and/or incontinence occur in 80% of individuals using prescription strength, are mild to moderate in severity, and improve after 1 to 2 months of therapy. Orlistat is approved for long-term use. It interferes with the absorption of fat-soluble vitamins, cyclosporine, levothyroxine, and oral contraceptives. A nonprescription formulation is also available.
• Lorcaserin is a selective serotonin receptor agonist (5-HT2c) approved for chronic weight management. Activation of central 5-HT2c receptors results in appetite suppression leading to modest weight loss as compared with placebo. Discontinue lorcaserin if 5% weight loss is not achieved by week 12. Common adverse effects include headache, dizziness, constipation, fatigue, and dry mouth.
• Phentermine in combination with topiramate extended release is indicated for chronic weight management. Doses are gradually titrated from phentermine 3.75 to 15 mg and topiramate 23 to 92 mg over 4 months but the drug should be stopped after 12 weeks if 5% weight loss is not achieved. Common adverse effects include constipation, dry mouth, paraesthesia, dysgeusia, and insomnia.
• Phentermine and diethylpropion are each more effective than placebo in achieving short-term weight loss. Neither should be used in patients with severe hypertension or significant cardiovascular disease. Short-term therapy is not consistent with current national guidelines for chronic management of obesity.

Orlistat 120 mg three times daily with each main meal containing fat

Orlistat 60 mg three times daily with each main meal containing fat

Lorcaserin 10 mg twice daily.

• Amphetamines should generally be avoided because of their powerful stimulant effects and addictive potential.
• Many complementary and alternative therapy products are promoted for weight loss. Regulation of dietary supplements is less rigorous than that of prescription and over the-counter drug products; manufacturers do not have to prove safety and effectiveness prior to marketing.