Obesity

David Arterburn

Oct 1, 2002 Issue

Clinical Evidence: A Publication of BMJ Publishing Group

Obesity

DAVID ARTERBURN, M.D., Health Services Research Fellow, VA Puget Sound Health Care System, Department of Veterans Affairs, Seattle, Washington

Am Fam Physician. 2002 Oct 1;66(7):1279-1280.

Questions Addressed

What are the effects of drug treatments for obesity in adults?

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Summary of Interventions

Trade off between benefits and harms

Sibutramine

Phentermine

Mazindol

Orlistat

Unknown effectiveness

Diethylpropion

Fluoxetine

Sibutramine plus orlistat

Likely to be ineffective or harmful

Phenylpropanolamine

Fenfluramine

Dexfenfluramine

Fenfluramine plus phentermine

To be covered in subsequent issues ofClinical Evidence

Ephedrine-caffeine, olestra, acarbose, cholecystokinin agonists, neuropeptide Y antagonists, beta₃-adrenergic agonists, leptin, growth hormone, surgery

Summary of Interventions

Trade off between benefits and harms

Sibutramine

Phentermine

Mazindol

Orlistat

Unknown effectiveness

Diethylpropion

Fluoxetine

Sibutramine plus orlistat

Likely to be ineffective or harmful

Phenylpropanolamine

Fenfluramine

Dexfenfluramine

Fenfluramine plus phentermine

To be covered in subsequent issues ofClinical Evidence

Ephedrine-caffeine, olestra, acarbose, cholecystokinin agonists, neuropeptide Y antagonists, beta₃-adrenergic agonists, leptin, growth hormone, surgery

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Definition	Obesity is a chronic condition characterized by an excess of body fat. It is most often defined by the body mass index (BMI), a mathematical formula that is highly correlated with body fat. BMI is weight in kilograms divided by height in meters squared (kg per m²). People with a BMI between 25 and 30 kg per m² are categorized as overweight, and those with a BMI greater than 30 kg per m² are categorized as obese.1
Incidence/Prevalence	Obesity has increased steadily in many countries since 1900.2 In the past decade, the prevalence of obesity in the United States has increased from 12 percent in 1991 to 17.9 percent in 1998.3
Etiology/Risk Factors	The etiology of obesity includes genetic and environmental factors. Obesity may also be induced by drugs (e.g., high-dose glucocorticoids), or be secondary to a variety of neuroendocrine disorders such as Cushing's syndrome and polycystic ovary syndrome.4
Prognosis	Obesity is a risk factor for several chronic diseases, including hypertension, dyslipidemia, diabetes, cardiovascular disease, sleep apnea, osteoarthritis, and some cancers.1 The relation between increasing body weight and the mortality rate is curvilinear, with mortality rate increasing in people with low body weight. Whether this is caused by increased mortality risk at low body weights or by unintentional weight loss is not clear.5 Results from five prospective cohort studies and 1991 national statistics suggest that the number of annual deaths attributable to obesity among U.S. adults is about 280,000.6
Clinical Aims	To achieve realistic gradual weight loss and prevent the morbidity and mortality associated with obesity, without undue adverse effects.
Clinical Outcomes	We found no studies that used the primary outcomes of functional morbidity or mortality. Proxy measures include mean weight loss (kg), number of people losing 5 percent or more of baseline body weight, and number of people maintaining weight loss.

Definition	Obesity is a chronic condition characterized by an excess of body fat. It is most often defined by the body mass index (BMI), a mathematical formula that is highly correlated with body fat. BMI is weight in kilograms divided by height in meters squared (kg per m²). People with a BMI between 25 and 30 kg per m² are categorized as overweight, and those with a BMI greater than 30 kg per m² are categorized as obese.1
Incidence/Prevalence	Obesity has increased steadily in many countries since 1900.2 In the past decade, the prevalence of obesity in the United States has increased from 12 percent in 1991 to 17.9 percent in 1998.3
Etiology/Risk Factors	The etiology of obesity includes genetic and environmental factors. Obesity may also be induced by drugs (e.g., high-dose glucocorticoids), or be secondary to a variety of neuroendocrine disorders such as Cushing's syndrome and polycystic ovary syndrome.4
Prognosis	Obesity is a risk factor for several chronic diseases, including hypertension, dyslipidemia, diabetes, cardiovascular disease, sleep apnea, osteoarthritis, and some cancers.1 The relation between increasing body weight and the mortality rate is curvilinear, with mortality rate increasing in people with low body weight. Whether this is caused by increased mortality risk at low body weights or by unintentional weight loss is not clear.5 Results from five prospective cohort studies and 1991 national statistics suggest that the number of annual deaths attributable to obesity among U.S. adults is about 280,000.6
Clinical Aims	To achieve realistic gradual weight loss and prevent the morbidity and mortality associated with obesity, without undue adverse effects.
Clinical Outcomes	We found no studies that used the primary outcomes of functional morbidity or mortality. Proxy measures include mean weight loss (kg), number of people losing 5 percent or more of baseline body weight, and number of people maintaining weight loss.

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Evidence-Based Medicine Findings

SEARCH DATE:CLINICAL EVIDENCE UPDATE SEARCH AND APPRAISAL SEPTEMBER 2001

Evidence-Based Medicine Findings

SEARCH DATE:CLINICAL EVIDENCE UPDATE SEARCH AND APPRAISAL SEPTEMBER 2001

Drug Treatments

CENTRALLY ACTING DRUGS

We found good evidence from systematic reviews and subsequent randomized controlled trials (RCTs) that sibutramine is more effective than placebo for promoting modest weight loss in healthy, diabetic, and hypertensive obese adults (BMI 25 to 40 kg per m²). Weight regain occurs after stopping treatment. We found no evidence about safety beyond two years of treatment. Limited evidence suggests that phentermine and mazindol, compared with placebo, result in modest weight loss over short periods in people more than 15 percent overweight. Weight regain was found after stopping treatment and after longer treatment periods. We found no major evidence of serious adverse events associated with phentermine or mazindol. We found insufficient evidence about diethyl-propion, fluoxetine, or sibutramine plus orlistat for weight loss. Dexfenfluramine, fenfluramine, and the combination of fenfluramine plus phentermine have been associated with valvular heart disease and pulmonary hypertension. Phenylpropanolamine has been associated with increased risk of hemorrhagic stroke.

ORLISTAT

Three systematic reviews and one subsequent RCT have found that orlistat plus a low-calorie diet modestly increases weight loss in adults with obesity compared with placebo plus diet. We found no evidence about effects on weight following discontinuation or on long-term adverse effects.

The views expressed in this article are those of the author and do not necessarily represent the views of the U.S. Department of Veterans Affairs.

Adapted with permission from Arterburn D. Obesity. Clin Evid 2002;7:538–47.

REFERENCES

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1. National Institutes of Health. Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults: the evidence report. Bethesda, Maryland: U.S. Department of Health and Human Services, 1998....

2. University of York, NHS Centre for Reviews and Dissemination. A systematic review of the interventions for the prevention and treatment of obesity, and the maintenance of weight loss. York, England: NHS Centre for Reviews and Dissemination, 1997. Search date 1995; primary sources Medline, EMBASE, Bids, Dare, PSY-CHLIT, bibliographies of review articles, and contributions from peer reviewers.

3. Mokdad AH, Serdula MK, Dietz WH, Bowman BA, Marks JS, Koplan JP. The spread of the obesity epidemic in the United States 1991–1998. JAMA. 1999;282:1519–22.

4. Bray GA. Obesity: etiology. UpToDate [serial on CD-ROM] 2000; 8(1). UpToDate, Inc., Wellesley, Mass., USA.

5. Bray GA. Obesity: overview of therapy for obesity. UpToDate [serial on CD-ROM] 2000;8(1). UpToDate, Inc., Wellesley, Mass., USA.

6. Allison DB, Fontaine KR, Manson JE, Stevens J, Vanitallie TB. Annual deaths attributable to obesity in the United States. JAMA. 1999;282:1530–8.

This is one in a series of chapters excerpted from Clinical Evidence, published by the BMJ Publishing Group, Tavistock Square, London, United Kingdom. Clinical Evidence is published in print twice a year and is updated monthly online. The complete text for this topic, as well as additional information, is available to subscribers atwww.clinicalevidence.com. This series is part of the AFP's CME. See “Clinical Quiz” on page 1147.