phentermine (the other half of fen/phen) suppresses appetite by causing a release of norepinephrine by the cells. phentermine alone is still available for treatment of obesity, but only on a short-term basis (a few weeks). The common side effects of phentermine include headache, insomnia, irritability and nervousness. Fenfluramine (the fen of fen/phen) and dexfenfluramine (Redux) suppress appetite mainly by increasing release of serotonin by the cells.
Unfortunately, both fenfluramine and dexfenfluramine were withdrawn from the market in September 1997 because of association of these two medications with pulmonary hypertension (a rare but serious disease of the arteries in the lungs), and association of fen/phen with damage to the heart valves. Since the withdrawal of fenfluramine, some have suggested combining phentermine with Fluoxetine (Prozac) - a combination that has been referred to as phen/pro. However, no clinical trials have been conducted to confirm the safety and effectiveness of this combination. Therefore, this combination is NOT an accepted treatment for obesity.
For more, please read the phentermine article.
Sibutramine (Meridia) suppresses appetite by increasing the amount of neurotransmitters serotonin and norepinephrine in the brain synapses. Unlike fenfluramine and dexfenfluramine, sibutramine does not increase release of these neurotransmitters from the cells. Instead, sibutramine inhibits the re-uptake of these neurotransmitters by the nerve cells. Therefore, the action of sibutramine is similar to that of anti-depressants that inhibit re-uptake of serotonin such as fluoxetine (Prozac) - a medication that has been used for years without known association with pulmonary hypertension or heart valve damage.
In December 1997, the United States Food and Drug Administration (FDA) approved sibutramine (Meridia) to treat obesity (both in attaining and in maintaining weight loss). According to FDA guidelines, Meridia should be considered only for patients with BMI of 30 or higher, or for those with a BMI of 27 or higher who also have other conditions (such as high blood pressure, diabetes mellitus, sleep apnea) that can improve with weight loss. Meridia should be accompanied by regular exercise and reduced-calorie diet.
Meridia is available in 5, 10, and 15mg capsules. The recommended starting dose is one 10 mg capsule per day. The dose of Meridia can be increased if weight loss is inadequate. Meridia should always be prescribed by doctors familiar with the patients’ medical condition, and familiar with the use and side effects of the medicine.
In clinical trials involving 6,000 individuals, Meridia produced statistically significantly more weight loss when compared to placebo (sugar pill). Generally, weight loss achieved with Meridia is modest. On average, patients treated with Meridia lost 5% to 10% of initial weight at various dosage levels. In two 12-month studies, maximal weight loss was achieved by six months, and statistically significant weight loss was maintained over 12 months.
Thus far, there are no reported increases in pulmonary hypertension or heart valve damage associated with the use of Meridia. Like any newly released medication, however, close monitoring will be necessary to determine the drug’s long-term safety and effectiveness. Certain side effects may not become apparent until months to years after release.
The known side effects of Meridia are mild and transient. They include dry mouth, headache, constipation and insomnia. Meridia also causes a small increase in average blood pressure and heart rate. But in some individuals, the increase in blood pressure can be more pronounced. Therefore, patients on Meridia should have regular monitoring of their blood pressure. Meridia should not be used in patients with uncontrolled high blood pressure, history of stroke, coronary heart disease, and congestive heart failure. For more, please read the Meridia article.
The next class (category) of drugs changes the metabolism of fat. Orlistat (Xenical) is the only drug of this category that is FDA approved. This s a new class of anti-obesity drugs called lipase inhibitors, or fat blockers. Fat from food can only be absorbed into the body after being broken up (a process called digestion) by digestive enzymes called lipase in the intestines. By inhibiting the action of lipase enzymes, Xenical prevents the intestinal absorption of fat by 30%. Drugs in this class do not affect brain chemistry. Theoretically, Xenical also should have minimal or no systemic side effects (side effects in other parts of the body) because the major locale of action is inside the gut lumen and very little of the drug is absorbed.
In clinical trials, Xenical with a moderately reduced calorie diet was found to be superior to placebo in achieving weight loss. The average patient in the one-year trial using Xenical lost about 10% of body weight. Many patients who continued treatment were able to maintain the weight loss. In addition, Xenical treated patients had statistically significant reductions in total and LDL cholesterol, blood pressure, and improvements in blood glucose levels after one year when compared to patients on only placebo and diet.
The clinical trials showed that Xenical was well tolerated. The most common side effects were gas, cramps and diarrhea. These side effects were believed to be due to the action of the drug (the unabsorbed fat in the gut can cause cramps and diarrhea). According to Hoffmann La- Roche, the maker of Xenical, these side effects generally occurred early in treatment and were of short duration.
Long-term decrease in fat absorption can cause deficiency of fat-soluble vitamins (such as vitamins A, D, E, K). Therefore, patients on Xenical should receive adequate vitamin supplementation. For more, please read the Vitamins and Calcium Supplements and Xenical articles.
In May 1997, the United States FDA Endocrinology and Metabolic Drugs Advisory Committee recommended the approval of Xenical as an adjunct to diet and exercise in treating obesity. After a temporary delay, the FDA has approved Xenical.
Revision date: July 4, 2011
Last revised: by Jorge P. Ribeiro, MD