What is the role of medication in the treatment of obesity?

Medication treatment of obesity should be used only in patients who have health risks related to obesity. Medications should be used in patients with a BMI greater than 30 or in those with a BMI of greater than 27 who have other medical conditions (such as high blood pressure, diabetes, high blood cholesterol) that put them at risk for developing heart disease. Medications should not be used for cosmetic reasons.

Medications should only be used as an adjunct to diet modifications and an exercise program.

Like diet and exercise, the goal of medication treatment has to be realistic. With successful medication treatment, one can expect an initial weight loss of at least 5 pounds during the first month of treatment, and a total weight loss of 10%-15% of the initial body weight. It is also important to remember that these medications only work when they are taken. When they are discontinued, weight gain often occurs.

The first class (category) of medication used for weight control cause symptoms that mimic the sympathetic nervous system. They cause the body to feel “under stress” or “nervous.” As a result, the major side effect of this class of medication is high blood pressure. This class of medication includes sibutramine (Meridia, which was taken off the market in the U.S. in October 2010 due to safety concerns) and phentermine (Adipex P). These medications also decrease appetite and create a sensation of fullness. Hunger and fullness (satiety) are regulated by brain chemicals called neurotransmitters. Examples of neurotransmitters include serotonin, norepinephrine, and dopamine. Anti-obesity medications that suppress appetite do so by increasing the level of these neurotransmitters at the junction (called synapse) between nerve endings in the brain.

Phentermine

Phentermine (Fastin, Adipex P) — the other half of fen/phen — suppresses appetite by causing a release of norepinephrine in the body. 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. Both fenfluramine and dexfenfluramine were withdrawn from the market in September 1997 because of association of these two medications with pulmonary hypertension (a rare but serious disease of the arteries in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.

Orlistat (Xenical, alli)

The next class (category) of drugs changes the metabolism of fat. Orlistat (Xenical, alli) is the only drug of this category that is U.S. FDA approved. This is a 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 lipases in the intestines. By inhibiting the action of lipase enzymes, orlistat prevents the intestinal absorption of fat by 30%. Drugs in this class do not affect brain chemistry. Theoretically, orlistat 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.

The U.S. Food and Drug Administration approved orlistat capsules, branded as alli, as an over-the-counter (OTC) treatment for overweight adults in February 2007. The drug had previously been approved in 1999 as a prescription weight loss aid, whose brand name is Xenical. The OTC preparation has a lower dosage than prescription Xenical.

Orlistat is recommended only for people 18 years of age and over in combination with a diet and exercise regimen. People who have difficulties with the absorption of food or who are not overweight should not take orlistat. Overweight is defined by the U.S. National Institutes of Health as having a body mass index (BMI) of 27 or greater.

Orlistat can be taken up to three times a day, with each fat-containing meal. The drug may be taken during the meal or up to one hour after the meal. If the meal is missed or is very low in fat content, the medications should not be taken.

The most common side effects of orlistat are changes in bowel habits. These include gas, the urgent need to have a bowel movement, oily bowel movements, oily discharge or spotting with bowel movements, an increased frequency of bowel movements, and the inability to control bowel movements. Women may also notice irregularities in the menstrual cycle while taking orlistat. Side effects are most common in the first few weeks after beginning to take orlistat. In some people, the side effects persist for as long as they are taking the drug.

People with diabetes, thyroid conditions, who have received an organ transplant, or who are taking prescription medications that affect blood clotting should check with their physician before using OTC orlistat (alli), since drug interactions with certain medications are possible.

A long-term decrease in fat absorption can cause deficiency of fat-soluble vitamins (such as vitamins A, D, E, K). Therefore, patients on orlistat should receive adequate vitamin supplementation.

Lorcaserin (Belviq)

In June 2012, the FDA approved Belviq (lorcaserin hydrochloride) as a weight-loss medication. The medication works by controlling appetite (via serotonin activation). According to the FDA data, nearly half the patients using the medication lost at least 5% of their starting weight, which is more than double that lost by patients in the control group. This was only true for patients without type 2 diabetes.

The medication is approved for patients who are obese (BMI >30) or overweight (BMQ >27) with one weight-related health issue. The predominant side effects were headache and dizziness, as well as fatigue. In patients with diabetes, low blood sugar was also a concern when taking Belviq.

Topiramate (Qsymia)

Qsymia is the newest medication approved for weight loss. It is a combination of phentermine and extended-release topiramate. As with the other medications, it is only approved for patients who are obese (BMI >30) or overweight (BMQ >27) with one weight-related health issue. According to the FDA data, a statistically significant greater proportion of the patients taking Qsymia achieved 5% and 10% weight loss. All patients in the study were also encouraged to eat a well-balanced, reduced-calorie diet.

It is important to note that Qsymia can lead to birth defects, and it is important for women to know that they are not pregnant before starting the medication. Other possible serious side effects include increased heart rate, eye problems (glaucoma), and suicidal thoughts. In patients with diabetes, low blood sugar was also a concern when taking Qsymia.

Naltrexone (Contrave)

This is a combination drug of naltrexone (an opioid antagonist) and bupropion HCL (an antidepressant medication that is an inhibitor of the reuptake of dopamine and norepinephrine). The main side effects observed with this medication are nausea, constipation, and headaches. The medication is contraindicated in patients with uncontrolled hypertension or a history of seizures.

The medication is approved as an adjunct to dietary changes and increased physical activity in adults with an initial BMI of 30 or greater or 27 or greater with at least one comorbidity.

Liraglutide (Saxenda)

Saxenda was approved in late 2014 as a weight-loss drug in combination with physical activity and diet modifications. It is a once-a-day injection (not a pill) that mimics a hormone related to digestion and appetite control (GLP-1) that is used in the management of type 2 diabetes. It activates areas of the brain involved in appetite regulation.

Saxenda has been linked to thyroid tumors in rats and mice as well as pancreatitis in humans.

The medication is approved as an adjunct to dietary changes and increased physical activity in adults with an initial BMI of 30 or greater or 27 or greater with at least one comorbidity.