A Review of Three Weight Loss Medications

Medications for Weight Loss When You Have Type 2 Diabetes

Millions of overweight Americans struggle with their weight every day. Diabetics, especially type 2 diabetics, are often told, when diagnosed, that they must lose weight. The most common strategies for weight loss are diet and exercise; however, when obese people are unable to lose weight using these techniques, medications may be prescribed to achieve a healthier weight. Here we look at three of these medications in order to educate our readers so that you can ask informed questions of medical teams.


Phentermine was first approved for the treatment of obesity in 1959, and it became very popular when articles were written about its efficacy in 1992.

It was used in combination with both fenfluramine (Pondimin) and dexfenfluramine (Redux) until studies showed a possible link between fenfluramines and heart-valve problems.

Today, phentermine alone is used as an appetite suppressant. It activates the adrenergic system (ie, the "fight or flight" response), causing it to release norepinepherine. For reasons not completely understood, this suppresses appetite.

The effectiveness of phentermine has been studied in a number of trials. If we exclude those trials where it was taken with other drugs, all clinical trials have been 20 weeks or less in length. These studies show that use of this medication results in an average weight loss of 6.6 pounds. It is approved for short-term use only (just for a few weeks).

Although phentermine is no longer prescribed with fenfluramines, it is used in combination with other medications. Some clinicians combine it with fluoxetine (Prozac), however; controlled studies are needed to show that this combination is safe and effective in the treatment of obesity. In fact, Eli Lilly, the maker of Prozac, has recommended that this drug combination should not be used at this time. Beware.

When taken alone, phentermine has some common side effects, including excessively rapid heart beat, increased blood pressure, restlessness, dry mouth, constipation, and sexual dysfunction. It should not be taken with monoamine oxidase (MOA) inhibitors or within 14 days of taking these medications. Persons with advanced atherosclerosis (hardening of the arteries), symptomatic cardiovascular disease, moderately to severely elevated blood pressure, hyperthyroidism, glaucoma, severe nervousness, or a history of drug abuse should not use phentermine.


Sibutramine (MERIDIA) was first studied as an antidepressant, but its effectiveness was limited. It was found, however, to be an effective appetite suppressant and was approved for use as an anti-obesity drug in 1998.

It works by extending the amount of time that serotonin and noradrenaline are free to work in the brain. The increased activity of these two chemicals results in appetite suppression and possibly in a small increase of energy expenditure. In trials of 6 to 12 months in duration, patients taking 15 mg per day lost an average of 12 to 14 pounds. This represents an average of about 10% of initial body weight.

The most important issue with respect to sibutramine is its potential to increase blood pressure to a very small degree (on average 1 to 3 mm Hg). Nevertheless, a small portion of patients (about 2%) experience significant increases in blood pressure. Therefore, it is not appropriate for treatment in obese patients with uncontrolled hypertension.

It is also contraindicated in persons with known cardiovascular disease or a history of stroke. All persons taking this medication should have their blood pressure closely followed.

Other side effects include headache, dry mouth, constipation, and insomnia.

One cross-sectional study and one short-term study found no evidence of an increase in valvular heart disease.

Persons taking any other centrally acting anti-obesity drugs (such as phentermine) or MAO inhibitors should not take sibutramine.

In addition, a rare syndrome (seratonin syndrome) theoretically may result when two or more serotonergic drugs (eg, sibutramine and fluoxetine) are taken together. No case of this has been reported to our knowledge, but the warning stands.


Until recently, all FDA-approved weight loss medications worked through decreasing calorie intake and to a lesser degree increasing calorie expenditure. There were no compounds that were safe and effective that altered the way the body stores calories in relation to body composition.

However, a new class of medication is aimed at blocking the absorption of calories, and Orlisat (Xenical), approved by the FDA in 1999, is the best studied of these compounds.

Orlisat works by blocking the digestion of fat in the intestine. By keeping the body from absorbing dietary fat, Orlisat decreases the total amount of energy from calories absorbed by the body. Taken at the recommended dose, this medication can block up to 30% of ingested fat.

For example, if a person eats 3000 calories a day with 35% of the calories from fat, Orlisat might block absorption of about 315 calories. Several short term studies (12 weeks) of Orlisat have produced weight loss of about .5 to 1 pound a week.

In fact, Orlisat has been studied in more than 4,000 persons followed for 1 or 2 years, and participants lost an average of 10% of their body weight in 1year.

In 2 years of treatment, participants experienced a loss of about 8% more of initial body weight. Additionally, Orlisat appears to improve blood cholesterol levels, which is thought to be due to the lower amount of fat absorbed by the body.

Because Orlisat blocks the absorption of fat in the intestines, the most common side effects are gastrointestinal. Studies indicate that about 20% of participants report at least one of these symptoms. However, symptoms tend to decrease over time. These side effects include increased stool size, possible stool softening, oily stools, and/or incontinence.

A minimally significant relationship between breast cancer and Orlisat originally slowed down the FDA approval of this drug.

To date there are no studies of the safety and efficacy of using Orlisat and other weight reducing medications. Since they act on different systems, it may be that they can be used together, but at this time combined treatment must be limited.

Weight Loss Medication Considerations

These anti-obesity medicines are only approved for the treatment of those who are seriously overweight or obese (defined as having a body mass index, BMI, of 27 or greater accompanied by obesity-related medical problems).

Phentermine and Orlisat have not been studied or approved for use in children or pregnant women. Sibutramine is approved for age 16 or older, but not for pregnant women. The use of weight loss medications in children and adolescents must be limited to approved clinical trials.

Persons who do not do well initially with these medications, generally do not do well with longer treatment. General guidelines suggest that those who do not lose at least 4 pounds in the first 4 weeks of taking a medication should discontinue it.

As we continue to view obesity as a chronic condition, the beliefs that some people will need life-long pharmaceutical treatment is gaining popularity. None of these medications has been studied for more than 2 years. Therefore, using any of them for a long period of time goes beyond our current knowledge. In the future, drug research hopefully will examine medications for their safety and effectiveness in both the short and long term of these and other anti-obesity medications in the severely obese.

In summary, none of these 3 medications should be used as the only method of weight loss, but they should be used in combination with diet and exercise.

In addition, counseling, nutrition, health education, and healthy lifestyle suggestions designed to promote positive changes in eating and exercise may be helpful for diabetics who are struggling with weight loss.


Updated on: April 14, 2011