• Prevalence of Obesity
• Definition of Obesity
• Causes of Obesity
• Why Be Worried?
• Medical Complications
• Treatments - Medications
• Previous Medications
• Phen-Fen Treatment
• Current Medications
• Future Medication + Qsymia
• Surgical Treatments
• Role of Physical Activity
• Successful Management

• Compulsive Overeating
• Diagnostic Criteria
• Eating Behaviors & Moods

Thyroid Hormone Treatment

The thyroid is a gland in the neck that is the major controller of metabolic rate. Metabolic rate determines the number of calories a person requires daily.

There is a wide range of thyroid hormone levels that are considered normal. An approach that became popular in the 1950's for weight reduction was to give excessive amounts of thyroid hormone to increase a person's metabolic rate and, therefore, decrease their weight. This approach seems logical; however, giving excessive thyroid hormone results in multiple complications including loss of muscle tissue, increased blood pressure, rapid heartbeat, strokes, and even death. Using excessive thyroid medication to artificially increase metabolism results in some loss of fat but marked loss of muscle mass. It eventually results in damage to the heart.

Unfortunately, with the paucity of medications available today, some physicians have resorted to giving excessive thyroid hormone to "improve" metabolism. This will result in some weight loss but is dangerous.

There are people who have low-functioning thyroids and do require thyroid hormone supplementation during their lifetime. When these individuals are placed on thyroid medication, they generally drop a few pounds, much of it water. However, unless the person has profound hypothyroidism (low thyroid condition), the addition of thyroid medication generally does not affect weight unless taken in dangerous amounts.

---

Dexfenfluramine

NOTE: The information below was initially written in early 1996 -- before dexfenfluramine was approved for use in the United States and obviously well before it was withdrawn from the market because of its association with Valvular Heart Disease. This information is provided to give a historical perspective on its use.

Dexfenfluramine (brand name REDUX), was an anorexic (appetite suppressant) drug used for years in Europe for treatment of obesity. It was approved for weight management on April 29, 1996 by the FDA.

Dexfenfluramine causes the release of serotonin, a neurotransmitter (or messenger) in the brain, from the pre-synaptic neurons (brain cells). The exact mechanism of action of serotonin is uncertain; however, increased levels of serotonin appear to stimulate an area in the brain (hypothalamus) that controls fullness ("satiety"), mood, sleep, body temperature, and other vital functions.

Dexfenfluramine was approved, primarily, on the basis of the International Dexfenfluramine (INDEX) Study. This study compared patients who were placed on either a placebo ("sugar pill") or dexfenfluramine for one year. All patients were provided behavior modification and dietary instruction.

Patients placed on placebo lost an average of 7.15 kilograms (~16 lbs.) compared to the dexfenfluramine group, which lost an average of 9.82 kilograms (~21 lbs.). In other words, the dexfenfluramine group lost on average an additional 5 3/4 lbs. after being on the medication for one year.

The use of dexfenfluramine resulted in both primary pulmonary hypertension, where the pressures in blood vessels feeding the lungs become elevated, resulting in an insidious shortness of breath, and to valvular heart disease, where the valves within the heart develop "vegetations" that interfere with normal cardiac functioning. In addition to these cardio-pulmonary complicatons, many individuals developed memory difficulty, depression, and impulsive behavior. These were the same conditions that resulted from the "phen-fen" combination used for weight loss (see next section).

Dexfenfluramine was withdrawn from the marketplace worldwide on 15 September 1997.

---

Phentermine combined with fenfluramine ("Phen/Fen Diet")

The Phen/fen diet was a very popular medication intervention for weight management in the mid-1990s. It too was withdrawn from the market on 15 September 1997.

Detailed information about this combination can be found in the next section.

---

SIBUTRAMINE - a medication that was used for weight management

Withdrawn from the marketplace October 2010

Sibutramine (brand name Meridia) was approved in November, 1997, by the U.S. F.D.A. for use in weight management. Sibutramine was developed in the late 80's as an antidepressant. It acts in areas of the brain that control not only mood and sense of well-being, but also appetite. It is a monoamine reuptake inhibitor that increases the level of norepinephrine, serotonin, and to a lesser extent, dopamine, available to brain cells (neurons) by interfering with the reabsorption of these substances by the neurons that initially release them. Norepinephrine, serotonin, and dopamine are neurotransmitters (or messengers) in the brain that lead to stimulation of other brain cells.

Sibutramine acts primarily by increasing satiety or fullness, although it may increase resting metabolic rate (the amount of energy consumed while resting), which leads to the ability to "burn" extra calories.

Unlike dexfenfluramine and fenfluramine, the medication does not cause release of serotonin from neurons. Tests done on humans show no evidence of valvular heart disease; and experiments done on animals show no evidence of neurotoxicity (brain damage), unlike the finding on test animals using the previously available medications fenfluramine and dexfenfluramine.

Clinical studies using sibutramine in conjunction with a low calorie diet, exercise, and behavior modification show that after 12 months, individuals placed on 15 mg. of sibutramine daily lost (on average) about 10 lbs (4.3 kg.) more than placebo-treated individuals. Some individuals, however, had a much larger weight loss. As with all weight loss medications, weight loss plateaus despite continued use of the medication.

Sibutramine has other beneficial effects that are independent of the weight loss. Sibutramine lowers insulin levels (which should help correct some of the metabolic derangements associated with long-standing obesity) and significantly raises the level of HDL-cholesterol ("good cholesterol").

Like all medications, sibutramine has side effects. It can cause constipation, insomnia, and agitation. Probably the most significant side effect is that it can raise blood pressure, sometimes significantly. This is the likely precipitating cause of problems that lead to the withdrawl of this medication from the markekplace.

In a large study of sibutramine published in 2010 (the SCOUT study - Sibutramine Cardiovascular OUTcomes Trial), there was a 16% increased risk of cardiovascular complications, namely non-fatal myocardial infarction ("heart attacks"), non-fatal strokes, resusicated cardiac arrests, and cardiovascular deaths.

Thus, this medication which was helpful to some individuals in helping manage weight was found to have an unacceptable risk/benefit ratio and is no longer available.