Weight Loss Drugs: What Works?

Laura A. Stokowski, RN, MS

December 13, 2010

Wanted: A Pill That Melts Fat

As Americans become more obese and the associated health problems reach epidemic proportions, the need for a safe and effective weight loss drug has become urgent. Over the years, this quest has been marked with short-lived triumphs and many defeats, leaving patients and clinicians with less than ideal weapons in the fight against obesity.

The few drugs that have actually reached the market in recent years promote weight loss either by boosting the body's basal metabolic rate, blocking the absorption of dietary fat, or suppressing appetite.People who take these drugs typically lose weight for the first 6 months until they reach a plateau that can't be surpassed without increasing exercise or caloric restriction.The problems with many of these agents have been a lack of proven long-term safety, and the fact that when such drugs are stopped, the weight is usually regained.

Most clinicians are aware that pharmacotherapy is not indicated as a first-line therapy for obesity, and should not be initiated until all nonpharmacologic attempts at weight loss (diet, exercise) have failed.^[1] It is also important to evaluate other medications that the patient may already be taking, as some may promote weight gain (eg, sulfonylureas, thiazolidinediones, and insulin), thereby negating the effects of anti-obesity drugs.^[2]

The decision to prescribe a weight-loss drug involves a careful assessment of the risks and benefits.^[3] As a general rule, an effective regimen should help patients lose at least 4 pounds in the first 4 weeks, or 5% of baseline weight in the first 3 months on therapy.

As researchers continue searching for an ideal weight-loss agent, clinicians must work with available therapies while awaiting newer drugs in the pipeline.

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Cite this: Laura A. Stokowski. Weight Loss Drugs: What Works? - Medscape - Dec 13, 2010.

Wanted: A Pill That Melts Fat
Currently on the Market
Withdrawn or Awaiting Approval
In the Pipeline
Potential Future Therapies
Final Thoughts on Anti-Obesity Pharmacotherapy
References
Sidebar: The Weight-Loss Imperative

The Weight-Loss Imperative

The classifications of "overweight" and "obese" are defined by BMI, calculated from a patient's weight and height. A person with a BMI ≥ 25 kg/m² is considered "overweight" and someone with a BMI ≥ 30 k/m²is considered^, "obese." Using these definitions, 68% of the adults in the United States are overweight, and 34% are obese.^[36]

The days when obesity was considered primarily a cosmetic problem are long gone. We now know that obesity is a complex disease that develops from a combination of genetic and environmental factors, and that the health implications of obesity are vast (see Table). In addition to elevated rates of type 2 diabetes, cardiovascular disease, and cancer, obesity can make surgical management more difficult and result in more postoperative complications.^[37,38]

Evidence of a survival benefit for obesity in select clinical situations is not enough to compensate for the overwhelming health risks, including death, associated with excessive body weight.^[4]

Table. Diseases Associated With Obesity^[39]

Organ System	Conditions
Cardiovascular	Hypertension, peripheral vascular disease, myocardial infarction, cerebral vascular accidents, peripheral venous insufficiency, thrombophlebitis, pulmonary embolism
Respiratory	Asthma, obstructive sleep apnea, obesity-hypoventilation syndrome
Metabolic	Type 2 diabetes mellitus, impaired glucose tolerance, hyperlipidemia
Musculoskeletal	Back strain/disc disease, osteoarthritis
Gastrointestinal	Cholelithiasis, gastrointestinal reflux disease, nonalcoholic fatty liver disease, hepatic cirrhosis, hepatic carcinoma, colorectal carcinoma
Urologic	Stress incontinence
Endocrine/Reproductive	Polycystic ovary syndrome, pregnancy/fetal abnormalities, male hypogonadism, endometrial, breast, ovary, prostate cancer, pancreatic cancer
Dermatologic	Intertriginous dermatitis
Neurologic	Pseudotumor cerebri, carpal tunnel syndrome
Psychologic	Depression, eating disorders, body image disturbance

Clinical Interventions for Obesity

The chief clinical intervention for obesity is lifestyle change, which usually involves counseling and behavioral therapy for reducing caloric intake and increasing physical activity. For patients who fail to lose weight with lifestyle intervention, pharmacotherapy and surgical approaches may be indicated.

The benefits of weight reduction, even on a fairly modest scale (5%-10% of body weight) are well documented. Among other benefits, weight loss is associated with a lower incidence of diabetes, hypertension, and dyslipidemia,^[40]improved urinary incontinence,^[41]and reduced inflammation in osteoarthritis.^[42]Patients with diabetes who lose even small amounts of weight have better metabolic control, fewer cardiovascular risk factors, and lower mortality rates.^[43,44] Continually losing and regaining weight (weight cycling), however, might be worse than maintaining a stable excessive weight. The evidence on weight cycling and threats to health is inconsistent, but raises the question of its safety.^[45]

Unfortunately, the degree of weight loss that is usually achieved with lifestyle intervention alone is insufficient. Efforts to lose weight are often thwarted by a compensatory slowing of the metabolism and high rates of recidivism.^[2]

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Weight Loss Drugs: What Works?

Wanted: A Pill That Melts Fat

Tables

References

Authors and Disclosures

Authors and Disclosures

Author(s)

Laura A. Stokowski, RN, MS

Sidebar

The Weight-Loss Imperative

Clinical Interventions for Obesity

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