Weight Loss Medications

By David A. Westbrock, MD, FACP, FACE

IF AT FIRST YOU DON’T SUCCEED…

Obesity is a biological and treatable disease. The question everyone should ask is “what is the risk to my health from not treating obesity?” And then one should ask, “what is the benefit and risk of using medications to treat obesity?” To understand the use of medications to treat obesity, let’s review their history.

The use of drugs for weight loss is as old as medical practice. From as long ago as 2000 BC, Indian remedies known as ayurvedic [eye-yer-VAY-dik] herbs were used for weight loss. These herbs included cayenne pepper, licorice root and cinnamon.

In the US, medications have been used to help people lose weight. Unfortunately, several obstacles have confronted those who used these drugs in the past. Thyroid extract was introduced in the late 1800s. To achieve effective weight loss it had to cause hyperthyroidism. In the 1930s, dinitrophenol [die-nigh-troh-FEE-null], a then popular drug, was one of the first drugs that carried FDA warnings and became restricted. Dinitrophenol use was associated with cataracts, blood disorders and death. Later, rainbow pills, a mixture of many unrelated drugs, such as digitalis, thyroid, and diuretics were found to cause multiple deaths. Then amphetamines [am-FET-ah-meens] were widely available until the late 1970s. Amphetamines are now restricted because they are addicting and may cause side effects on the heart and nervous system.

In the 1990s the drugs fenfluramine [fen-FLOO-ra-meen] (previously marketed as Pondimin) and dexfenfluramine [dex-fen-FLOO-ra-meen] (Redux) were used to treat obesity. Fenfluramine was used in combination with phentermine [fen-ter-meen] (Fen-Phen). Fenfluramine and dexfenfluramine were taken off the market after reports of heart valve problems in association with their use.

A popular decongestant medication used for appetite suppression, Dexatrim, was also withdrawn by the FDA. Dexatrim was associated with an increased risk of stroke in 1 in 100,000 women who took the drug for the first time.

With this history, it is not surprising that many doctors shy away from using any obesity medications.

WHERE ARE WE NOW?

In the 1960s and 1970s benzphetamine [benz-FEHT-ah-meen], phendimetrazine [fen-dih-MET-rah-zeen], diethylpropion [die-ethyl-PRO-pree-on] and phentermine (marketed as Tenuate and Adipex) were introduced into the market. For all of these medications, weight loss is approximately 2-3 times as much as weight loss with a placebo drug (sugar pill). These medications are still available today. At the time of their approval, the recent experience with amphetamines led the Food and Drug Administration (FDA) to limit these medications for short-term use (up to 12 weeks). The concern at the time was that these medications could be addictive, like the amphetamines. This was an understandable concern at the time. Additionally, obesity was not considered a disease back then, like it is now.

We now understand that treating obesity and overweight require a long-term commitment. For this reason, intermittent use of these medications may be considered. Intermittent use has been shown to give similar results to continuous use for phentermine. In my experience, weight regain is common after stopping the medications if the patient is not closely supervised.

There are only two FDA-approved obesity drugs for extended use.

Orlistat is available over the counter as Alli, or by prescription as Xenical [ZEN-ih-kal]. It works by blocking the absorption of dietary fat. It is less effective in people who eat a low-fat diet. When fat is not absorbed by the gut it will go right through. Possible side effects of orlistat include oily stools, loose stools, frequent stools, and stool accidents. These side effects are easily avoidable by eating less fat and using soluble [SAHL-you-bull] fiber. Soluble fiber holds the oily residue in the gut making it less irritating. To prevent fat-soluble vitamin malabsorption, a multivitamin should be taken every night, away from meals.

Sibutramine [sigh-BYOO-trah-meen], available as Meridia, works on the brain to cause early fullness. Sibutramine may raise metabolism. It is not habit forming. Sibutramine increases serotonin [seh-roh-TONE-in] levels in the brain and needs to be used with caution in patients also using antidepressants known as SSRIs (selective serotonin reuptake inhibitors). These include, for example, Prozac, Zoloft, Celexa and others. Using sibutramine and these antidepressants together may overstimulate the central nervous system.

In November 2009, the FDA issued a warning about sibutramine. Preliminary data from the SCOUT trial suggests that patients using sibutramine have a higher number of cardiovascular events (heart attack, stroke, resuscitated cardiac arrest, or death) than patients using a placebo (sugar pill). Although this is a preliminary review of the data, sibutramine and other medications that act on the brain have to be used with caution. Talk to your doctor about the benefit and risk of these medications. Clearly, the blood pressure and cholesterol have to be treated independently of the weight.

Orlistat and sibutramine cause a loss of 5-10% of body weight. Most weight is lost within the first 6 months. When continued beyond the initial weight-loss phase, orlistat and sibutramine help prevent weight regain.

There are, of course, many products touted as natural remedies for weight reduction. Two are recently the most popular, and they include acai, a fruit of Brazilian origin and hoodia, a product of the Kalahari Desert in Africa. Acai has anti-oxidant properties and is being studied for preventing hardening of the arteries and as an anti-cancer agent, but it has no proven benefit as a weight loss drug. Hoodia is touted in advertisements as a natural product that, as used by African bushmen, can suppress appetite. While this claim is true, no evidence is yet available (although it is being researched) to support claims that commercially available products of hoodia are either safe or effective. As health care consumers resort to natural products from health food stores and Internet outlets, it is very important that the use of any of these products be considered only after consulting a doctor.

Metformin is now the most commonly prescribed drug as initial therapy for type 2 diabetes. It had been, until recently, the only drug for diabetes that has aided in weight loss. Exenatide and pramlintide are injectable medications recently approved for the treatment of diabetes. Both have been shown to improve blood sugars after meals as well as fasting. Both drugs slow stomach emptying, and though nausea is the most common side effect, the drugs have been shown to cause weight loss. Although these anti-diabetic medications are not FDA approved for weight loss, they have this added benefit. In addition, metformin has been shown to prevent diabetes.

Topiramate, zoniamide and lamotrigene are anti-seizure drugs that generally result in weight reduction. They are used “off-label” to help with weight management, because they are not currently approved by the FDA for weight loss. Several medications may result in weight gain. These include many of the most widely used medications to improve mental health. Ask your doctor about the weight effects of medications that you are being prescribed.

THE FUTURE – THEN TRY, TRY AGAIN…

The future of obesity medications is very positive. It is recognized that obesity is not only a serious health problem for the individual patient, and new drugs to help are constantly being studied. This includes several other medications that track the chemical messages between fat cells, the stomach and intestines, and the brain.

Obesity medications should always be used in addition to ongoing lifestyle changes, with improved nutrition and increased physical activity. And remember that cardiovascular risk factors such as high blood pressure and high cholesterol have to be aggressively treated independent of the weight.

David A. Westbrock, MD, FACP, FACE, has been in private practice for nearly 30 years in Dayton, Ohio. He is certified by the American Board of Internal Medicine in Internal Medicine and Endocrinology/Metabolism. He received his undergraduate degree from the University of Dayton and his medical degree from the Ohio State University. Dr. Westbrock is an associate clinical professor of medicine at Wright State University. Dr. Westbrock is one of the Dayton area’s premier obesity experts. He created New Profile Weight Management Center in 1998. In it, he aims to create a permanent solution for patients’ health as it relates to weight management as well as a model for preventative health care in other chronic disease states. A Dayton area resident for the vast majority of his life, Dr. Westbrock has been married for 35 years and has three children.