Obesity 2011: History of Drugs

history weightloss drugsToday at Obesity 2011, the Obesity Society’s 29th annual meeting, a symposium was presented on Drugs and Obesity, Where Do We Go From Here? The symposium included 3 talks. The first talk, given by Dr. George Bray, focused on a history of obesity drug development.

Starting with the seventeenth century, Bray went through a brief history of obesity treatment prior to the twentieth century. Beginning with treatments such as bleedings and recommendations such as ‘violent exercise’, avoiding ‘excessive drinking’, and using castille soap, many have been looking for a medical way to treat obesity. For several centuries, drinking vinegar was believed to dissolve fat.

In 1892, thyroid gland extract was the first ‘drug’ used to treat obesity. It began a less-than-successful line of attempts at finding safe and effective drug treatments. In the 1930’s, one of the earliest drugs used to treat obesity was introduced: Dinitrophenol-1. Although the drug led to some weight loss, it also caused unanticipated adverse effects including cataracts, blindness, and deaths. At this time, the FDA had no authority over the toxicity drugs, and no control at all over obesity drugs, because obesity was not a considered disease; it was categorized as a cosmetic condition. In response to several deaths caused by use of Dinitrophenol-1, the question was posed – which exemplified the attitude of the time – “Why is a drug with so great potential dangers justified in the treatment of a relatively benign condition such as obesity?” In the late 1930’s the FDA’s role expanded and they became responsible for regulating drug toxicity in general. However, the dismissive attitude of drug-based obesity treatment continued into the mid-twentieth century. The FDA commissioner in the 40’s called the use of an obesity drug “wholly irrational”, again perpetuating the belief that serious medicine should not be used for a condition as ‘minor’ as obesity.

Post World War II, several drugs were introduced in an attempt to treat obesity, but with side-effects ranging from addiction to strokes to death, their use has been intermittent or stopped. For several decades the FDA attempted to regulate the toxicity of drugs. It wasn’t until 1962 that the Kefauver-Harris Amendment (the Drug Efficacy Amendment) required efficacy as well as safety, in order for a drug to be approved by the FDA. In 1965, the first weight loss drug trials began appearing.

The most well known of the weight loss drugs in the last 50 years has be the Fen Phen combination. An NIH-funded study showed significant weight loss. In 1996, sales of Fen Phen peaked to a level previously unseen in weight loss drugs. But studies suggesting that patients could develop new heart valve problems prompted wide-spread media attention and the recommendation of the FDA in 1997 that Fen-Phen no longer be prescribed.

Since Fen-Phen, the last 14 years have seen a variety of attempts at finding successful obesity treatment drugs. In a subsequent talk, Dr. Kenneth Fujioka spoke about the current state of obesity drugs. There are only two drugs currently approved for the treatment of obesity: Phentermine or Orlistat. With the obvious importance of drug regulation, many believe that the balance between safety, efficacy, appropriate testing, and the desire to treat obesity medically, is a balance that has not yet been found. We spoke to Dr. Gregory Walton of WeightWise Bariatric Program. He said, “Pharmacologic anti-obesity efforts have an ominous history with the FDA. In fact, several commercially available drugs have been pulled from the market by the FDA – citing efficacy and safety concerns.” Dr. Walton added, “At the same time obesity is being recognized as a significant problem, we have fewer weapons in our armamentarium to battle the epidemic. We believe for a drug to be more than marginally successful against obesity, it will need to be multivalent – that is, it will need to attack several pathways simultaneously. Without dramatic effects, the FDA will apparently be reluctant to approve pharmacologic agents.”

Dr. Mark Fusco of LifeShape Bariatric Center in Florida added, “The need to develop new pharmacologic agents to help patients with obesity is urgent. The challenge for pharmaceutical researchers and manufacturers is that these agents by necessity need to be given over long periods of time. They need to demonstrate a significant safety profile to win approval from governmental agencies that are increasingly risk averse.”

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  1. New Article: Obesity Drugs, A History « - October 12, 2011

    […] In Dr. Walton’s comments, he explained that it is challenging to get obesity drugs approved by the FDA. He said “for a drug to be more than marginally successful against obesity it will need to be multivalent – that is, it will need to attack several pathways simultaneously. Without dramatic effects, the FDA will apparently be reluctant to approve pharmacologic agents.” Dr. Mark Fusco agreed with Dr. Walton, saying that “the agents need to demonstrate a significant safety profile to win approval from governmental agencies that are increasingly risk averse.” As of now, there has been very little success in the treatment of obesity with drugs. You can read more extensive coverage of the session, and more of Dr Walton’s comments, here. […]