The Changing Landscape of Obesity Management: Novel Pharmacological Treatments

The Changing Landscape of Obesity Management: Novel Pharmacological Treatments
The Changing Landscape of Obesity Management: Novel Pharmacological Treatments
BACKGROUND/EPIDEMIOLOGY
More than one-third of U.S. adults (over 72 million people) and 17% of U.S. children are obese.According to the World Health Organization (WHO), a body mass index (BMI) of 25–29kg/m2 is considered overweight, while a BMI of  >30kg/m2 is considered obese.2 During the past several decades, obesity rates doubled for adults and tripled for children. Recently, reports show differences in obesity prevalence by race and ethnicity. The National Health and Nutrition Examination Survey showed that among women aged 20 years and older, 51% of non-Hispanic black women were obese, compared with 43% of Mexican Americans and 33% of whites.1 In 2008, overall medical care costs related to obesity for U.S. adults were estimated to be as high as $147 billion. People who were obese had medical costs that were $1,429 higher than the cost for people of normal body weight.1

CURRENTLY AVAILABLE PHARMACOLOGICAL TREATMENTS FOR OBESITY
3
Currently, there are five classes of medications that are used for weight management:

FDA-Approved Treatments
     - Dopaminergic agents (e.g., phentermine, phendimetrazine, diethylpropion)

     - Pancreatic lipase inhibitor (e.g., orlistat)
  

Off-Label Treatments
     - Antidepressant agents (e.g., bupropion HCl)

     - Antiepileptics (e.g., topiramate, zonisamide)

     - Antidiabetic agents (e.g., metformin)

Dopaminergic agents act as appetite suppressants by stimulating dopaminergic neurotransmitter pathways in the brain. These drugs are approved for short-term use only. Possible side effects of this class may include insomnia, nervousness, euphoria, hypertension, tachycardia, and dry mouth. Phentermine is the most commonly prescribed appetite-suppressant in the United States.3 Clinical studies have shown that weight loss is greatest in the first week of therapy for both drug and placebo subjects and tends to decrease in succeeding weeks, although this mechanism is not well established or defined. The amount of weight loss associated with these drugs varies from trial to trial, depending on physician-investigator interaction, the population treated, and the diet prescribed. A 36-week randomized controlled trial (RCT) in 108 overweight women demonstrated a mean weight loss of 12.2kg (13%) with phentermine (30mg daily) compared to 4.8kg (5.2%) with placebo (P<0.001).In a six month RCT in 69 obese patients, diethylpropion was shown to have a mean weight loss of 9.3kg, compared to 3.1kg for placebo (P<0.001).5

Orlistat, a pancreatic lipase inhibitor, acts on the lumen of the small intestine and reduces fat absorption by about 30%. Possible side effects of this class include reduced absorption of fat-soluble vitamins, soft stools, and anal leakage. In a 52-week RCT, the orlistat group lost an average of 10.3kg by the end of Year 1. During Year 2, patients who continued orlistat regained, on average, half as much weight as those patients switched to placebo (P<0.001). Patients switched from placebo to orlistat lost an additional 0.9kg during Year 2, compared with a mean regain of 2.5kg in patients continued on placebo (P<0.001).7

Sibutramine is part of a class of drugs that inhibits the reuptake of norepinephrine and serotonin, thereby increasing the secretion of norepinephrine and serotonin into the synaptic neural cleft. This action is thought to suppress appetite and increase satiety. This drug, however, was pulled off the market in 2010 and is no longer available in the U.S., due to an increased risk of cardiovascular events such as heart attacks and stoke.6

Treatments such as buproprion, topiramate, zonisamiade, and metformin, that are not FDA-approved for obesity, have shown in clinical trials to promote short-term weight loss and can be prescribed off-label. Clinical data show that bupropion, an antidepressant, can maintain modest weight loss in patients for up to one year. Antiepileptic agents such as topiramate and zonisamide are still being evaluated for their efficacy in obesity. Metformin may be most useful in patients with obesity and type 2 diabetes. It is believed that metformin exerts its weight-loss effects by acting as an appetite suppressant.3