• Testing and treatment for any secondary causes of obesity and comorbid conditions
• Manage with lifestyle measures for 3–6 mo; if weight loss is insufficient to lower long-term health risks, consider pharmacologic or surgical therapy
• If BMI ≥ 30 or if BMI > 27 in patient with obesity-related risk factors (i.e., diabetes, hypertension, or hyperlipidemia), consider pharmacologic therapy
• If BMI ≥ 40 or if BMI > 35 in patient with obesity-related risk factors, refer for surgery
• Goal for pharmacologic or surgical treatment, together with lifestyle measures: sustained loss of ≥ 5% of initial body weight

Diet Modification

• Caloric restriction
  • Without additional interventions such as exercise or pharmacologic therapy, ≥ 95% of initially lost weight will be regained within 5 yr
• Dietary-fat restriction
  • Restriction of dietary fat to 25%–30% of calories results in significant but modest weight loss; response is highly varied
• Dietary-carbohydrate changes
  • Increasing dietary carbohydrate intake while lowering total fat intake results in modest weight loss (~ 2–4 kg) in overweight and obese persons if the additional carbohydrates come from fruits, vegetables, and grain products
  • Can help sustain weight loss after a period of caloric restriction
  • Severe carbohydrate restriction (< 25 g/day) may lead to modest spontaneous weight loss by inducing ketogenesis, but sustainability of weight loss and long-term health outcomes are unclear
• Dietary-protein changes
  • Protein intake should be limited to ~ 10%–15% of daily calories
  • Obese patients can have significantly greater weight loss on a high-protein diet (~ 30% total calories) than on a regular or a low-fat, high-carbohydrate diet, but potential adverse outcomes have not been adequately studied
  • High protein intake may be associated with intestinal cancers, bone disease, and renal disease
  • High protein intake increases glomerular filtration rate, which may harm patients with existing renal disease or diabetes

• Weight loss of 1–4 kg (2.2–8.8 lb) over 1 yr in randomized, controlled studies
• Can help sustain weight loss after a period of caloric restriction
• American College of Sports Medicine recommends a minimum exercise level of 1,000 kcal/wk for reducing body weight, but 2–3 times that level is more effective for significant, sustained weight loss
• Should be encouraged because of health benefits attributable to fitness

• Initial treatment of overweight and obese patients should include dietary-fat restriction and increased activity using individualized, sustainable behavioral and lifestyle changes
• Dietary-fat restriction and exercise can improve lipid levels, increase insulin sensitivity, and reduce risk of progression of cardiovascular disease and of onset of type 2 diabetes
• If lifestyle measures are not effective, medical and surgical treatments can be considered

• Effective in achieving weight loss of up to 10% of initial body weight for at least 2 yr
• In most studies, patients began a hypocaloric diet (daily caloric intake reduced by 500–1,000 kcal) before drug treatment
• Weight loss with obesity agents varies considerably, usually < 10% of baseline weight
• Weight loss is greatest during the first 3–6 mo, followed by a plateau at a new lower weight even with continued therapy
• Rapid weight regain toward baseline follows discontinuance of medication
• Treatment should be continued indefinitely unless the weight is regained or significant side effects develop

• Phentermine
  • Inhibits appetite
  • Average weight loss, 8.7 kg (19.2 lb)
  • May cause anxiousness, insomnia, palpitations, dry mouth, vasospasm, psychosis, and ischemic events
  • May be used long term if weight loss sustained
  • Dose: 30 mg resin, or 15 or 37.5 mg tablets; doses > 37.5 mg not recommended
  • Cost/mo: $23

• Sibutramine
  • Inhibits appetite
  • Average weight loss, 7.0 kg (15.4 lb)
  • Associated with improvements in lipid levels and glycemic control in diabetes
  • May cause dry mouth, constipation, insomnia, palpitations, and headache
  • Raises blood pressure and pulse rate, which should be monitored; contraindicated in patients with cardiovascular disease, heart failure, arrhythmia, or stroke
  • Dose: 5–15 mg/day
  • Cost/mo: $110
• Orlistat
  • Reduces fat absorption
  • When combined with a calorie-restricted diet, results in an average weight loss of 7.24–13 kg (16 to 28.7 lb) and significant reduction in levels of total and LDL cholesterol
  • Blood pressure and insulin levels decrease and glycemic control improves with weight loss
  • Side effects include abdominal discomfort, flatus, fecal urgency, oily spotting, and fecal incontinence
  • To minimize side effects related to fat malabsorption, candidates for orlistat treatment are first placed on a 30%-fat–restricted diet
  • Contraindicated in patients with existing malabsorptive states
  • Patients should take a daily multivitamin supplement during therapy
  • Dose: 250 mg with each meal
  • Cost/mo: $260

• Selective serotonin reuptake inhibitors
  • Weight loss is modest and short-lived
• Bupropion plus modest daily caloric restriction
  • Can produce weight loss
  • Contraindicated in patients with seizures, anorexia nervosa, and bulimia
  • Dose: 300–400 mg/day
  • Cost/mo: $134
• Growth hormone, sex steroids
  • No clear benefit for obesity unless there are clear hormonal deficiencies

• Systemic steroids (glucocorticoids)
  • Alternatives
    • Asthma: inhalers
    • Cancer chemotherapy: non–glucocorticoid-based regimens
    • Rheumatoid arthritis: methotrexate and remitting agents
• Antidiabetic drugs (insulin, sulfonylureas, thiazolidinediones)
  • Alternatives
    • Metformin
    • Acarbose
• Antiepileptic drugs (gabapentin, valproic acid)
  • Alternatives
    • Lamotrigine
    • Topiramate
• Antipsychotic agents (clozapine, olanzapine, risperidone, sertindole)
  • Alternatives
    • Haloperidol
    • Ziprasidone
• Antidepressants (tricyclic antidepressants, monoamine oxidase inhibitors, mirtazapine)
  • Alternatives
    • Bupropion
    • Nefazodone
    • SSRIs
    • Venlafaxine

• Can produce weight loss to up to 30% of initial weight for at least 5 yr
• Best therapy to reverse or prevent type 2 diabetes and sleep apnea
• Improvements in hypertension and lipid levels more closely related to amount of weight lost
• Anatomically irreversible in most cases
• Potentially high postoperative complication rate, including infections, wound complications, and pulmonary symptoms
• Perioperative death rates, 0.2%–1.3%; complication rates, 13%–36%

Best References

Bray GA: J Clin Endocrinol Metab 89:2583, 2004 [PMID 15181027]

Buchwald H, et al: JAMA 292:1724, 2004 [PMID 15479938]

Schwartz MW, et al: Nature 404:661, 2000 [PMID 10766253]

Snow V, et al: Ann Intern Med 142:525, 2005 [PMID 15809464]