Genetic Variants Affect Weight Loss Drug Effectiveness

Obesity affects about one out of three adults in the United States. Because obese people are at increased risk of high blood pressure, diabetes, cardiovascular disease, and other health problems, many authorities consider it one of the most significant public health problems in the developed world.

Of course, diet and exercise are important parts of maintaining a healthy weight, but some people need a little more help. Sibutramine (marketed by Abbott Laboratories as Meridia ® in the U.S.) is a drug that creates a feeling of fullness, prevents the decline in metabolic rate usually associated with low-calorie diets and causes weight loss, especially when combined with behavioral therapy.

Genetics and Responsiveness to Treatment

But success with sibutramine is variable — for some people it just doesn’t work. New research, published in the October issue of Gastroenterology, shows that genetic differences might be to blame.

“Our results suggest the genetic make-up of patients could predispose their responsiveness to a drug. This could have important implications for the future of personalized molecular-based or individualized medicine,” said the study’s lead author Dr. Michael Camilleri in a statement.

Using a sample of 158 overweight and obese people, researchers at the Mayo Clinic tested the effectiveness of sibutramine therapy compared to placebo over 12 weeks. All participants also received behavioral therapy.

Study Results

The researchers found that weight and body mass index were significantly reduced in patients taking sibutramine compared to placebo, as was expected from previous research. But upon further inspection of the data, the researchers found that only people with certain versions of three different genes experienced significant weight loss.

People with a variant in the GNβ3 gene, had success with sibutramine, losing about 13 pounds. People with another variant in the α2A gene, lost even more weight — more than 17 pounds on average.

The third genetic marker scientists investigated, known in the scientific literature as 5-HTTLPR, is a stretch of DNA that comes in a long and short form. Only people with one or two copies of the short version of this marker had significant weight loss with sibutramine.

“Genetic variations may help select obese patients who are more likely to experience improved outcome with this treatment. Since the different markers were present in almost 50 percent of patients, the inclusion of screening for the genetic markers before prescribing the medication may even be cost-effective from a public health perspective,” Camilleri said.