By Craig Primack MD, FAAP Obesity Medicine Specialist Co-director, Scottsdale Weight Loss Center
Editor's Note: Qnexa has been renamed Qsymia and as of September 18, 2012 is available in pharmacies.
Qnexa is a new, potent, effective and safe weight-loss drug that will help in the fight against obesity; it is poised to become the first FDA-approved weight-loss pill in 13 years. Qnexa is a combination pill of two medicines already on the market: phentermine and extended-release topiramate. Both drugs have been shown to help weight loss when used as part of a comprehensive weight-loss program led by a medical obesity specialist physician and together seem to be synergistic, not just additive.
Why are medical obesity specialists so excited for Qnexa?
The last time a new weight-loss drug was approved was in 1999. In these 13 years, the numbers of the overweight and obese have increased significantly. It is now estimated that 2 of every 3 people are overweight, and about 30% of the population is obese. The studies that looked at Qnexa showed 9.8-14.7% weight loss, depending on the dose and the amount that you are overweight. A 10% weight loss is enough to improve many weight-related diseases such as pre-diabetes, high blood pressure, high cholesterol and sleep apnea.
I have been prescribing this combination of drugs since first hearing about the Qnexa studies back in 2009. At the time, we were using both phentermine and topiramate for weight-loss – but individually. Their side effects are quite different so that some patients did better on one drug and some did better on the other.
If there was a reason to be put on one or the other drug, we did so. For example, if a patient had migraines, we chose topiramate. If they were free of heart disease, we chose phentermine. Now, as my experience with the combination has grown, we commonly start with one drug, more often it is phentermine. For some, the phentermine’s effect is incomplete and adding topiramate has really helped.
Like all drug therapies, patients respond differently to the same drug. For a small few, their hunger is so little that we have to decrease the dose so that they actually eat regularly. For most, adding the second drug boosts the appetite-suppressant effect and there is less hunger. In a small percentage, the second drug does not seem to add much or the side effects are too much, and we go back to a single drug therapy. In my practice, I always use medications in combination with dietary change, exercise, a behavior-based class series, accountability, and adequate sleep counseling.
What is phentermine?
Phentermine was initially approved as a weight-loss drug in 1959. Phentermine is considered a stimulant-type appetite suppressant. Its major site of action is centrally in the brain. It effectively decreases hunger and gently increases metabolism. Phentermine has been studied numerous times for weight loss (in combination with diet and behavioral modification), as well as in the maintenance of weight loss.
What is topiramate?
Topiramate (Topamax®, Janssen Pharmaceuticals, Inc., Titusville, New Jersey) was originally approved in 1996 as a migraine-preventative treatment and seizure medication. Weight loss was initially seen as a side effect and it has now been studied directly for use in weight loss and in binge-eating disorder.
The mechanism of action of topiramate is not entirely known. One mechanism that may contribute to its weight loss effects is its effect on taste. Many patients taking this drug report certain foods taste different, especially diet colas. With altered taste sensations, some of the reward from eating certain foods may be altered.
Who should consider using this drug?
The final requirements have not been released, but I suspect that someone will need either a body mass index (BMI) of 30 or BMI greater than 27 with certain cardiac risk factors, such as diabetes, high blood pressure and high cholesterol. If used, it should always be used as part of a complete weight-loss program. I believe its effects will be best when used with diet, exercise and behavior modification. It will best be used long-term as long as you are getting benefit from its use.
Who should not use this drug?
This drug should absolutely not be used with patients with pre-existing heart disease or women who are going to become pregnant, as it has been shown to slightly increase the risk of birth defects, such as cleft lip and palate. There are several other possible side effects that should be discussed with the doctor who prescribes it for you, prior to starting it. A few possible side effects are rapid heart rate, temporarily increased blood pressure, forgetfulness, and kidney stones.
When will it be available?
Achieving approval of this drug has not been easy. Vivus Inc., the company who will make Qnexa, submitted their application to the United States Food and Drug Administration (FDA) initially in 2009. This application was based on the results of a few published studies on weight loss, EQUIP and CONQUER. In January 2011, the FDA asked Vivus to further look at the possibility of birth defects in the drug before approval. The FDA also expressed concern about other possible side effects, including suicidal thoughts, heart palpitations, and memory lapses. On February 22, 2012, a subcommittee of the FDA voted 22 to 2 to approve the drug. On July 17, 2012, the full FDA is expected to follow the sub-committee recommendation and approve Qnexa. It will likely be 3 to 6 months after approval before it is available for use.
Qnexa, the first new weight-loss drug since 1999, is long overdue. It will be a good tool in the treatment of obesity. Combination drugs have been shown to improve compliance in taking all doses of a drug as prescribed. Although both phentermine and topiramate will remain available on their own in generic forms, Qnexa will be the strongest combination drug available to treat obesity and being overweight. Finally, it is important to remember that Qnexa is just one of many tools for weight loss. Its best effects will be seen as part of a complete program for weight loss that includes diet, exercise, behavior change, and adequate sleep.
Allison DB, Gadde KM, Garvey WT, et al. Controlled-release phentermine/topiramate in severely obese adults: a randomized controlled trial (EQUIP).
Obesity (Silver Spring). 2012;20(2):330–342.
Gadde KM, Allison DB, Ryan DH, et al. Effects of low-dose, controlled- release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): a randomised, placebo-controlled, phase 3 trial. Lancet. 2011;377(9774):1341–1352. Epub 2011 Apr 8.
Garvey WT, Ryan DH, Look M, et al. Two-year sustained weight loss and metabolic benefits with controlled- release phentermine/topiramate in obese and overweight adults (SEQUEL): a randomized, placebo- controlled, phase 3 extension study. Am J Clin Nutr. 2012;95(2):297–308. Epub 2011 Dec 7.