Obese adults who took a combination of two drugs already approved to treat obesity, migraine and epilepsy achieved up to 10% weight loss in 12 months, according to results of a clinical trial in the US published in The Lancet this week.
First author Dr Kishore M. Gadde, director of the clinical trials program at Duke University Medical Center in Durham, North Carolina, told the press that participants who took the combination drug achieved an average weight loss of 8.6% compared to those who took placebo.
“This kind of weight loss, coupled with significant reductions in cardiometabolic risk factors represents a potentially important advancement in the management of obesity”, said Gadde, who until 2008 was a paid consultant with Vivus, the drug company that sponsored the trial.
Participants treated with a controlled-release combination therapy of phentermine and topiramate also experienced significant reductions in blood pressure and hemoglobin A1C (a measure of long term control of type 2 diabetes). Compared to placebo, either of the two doses of the combination drug also resulted in improvements in cholesterol, triglycerides and inflammatory markers, including C-reactive protein.
Vivus is seeking US Federal Drug Administration (FDA) approval to market the combination drug under the trade name Qnexa. in October last year, the FDA ruled not to approve the drug as a treatment for obesity and asked Vivus for more safety data.
Topiramate is an anticonvulsant approved by the FDA for use alone or with other medications to treat patients with epilepsy who have certain types of seizures.
Phentermine, an appetite suppressant, is already approved for the short-term treatment of obesity.
But last month, the FDA issued a Drug Safety Communication about the use of topiramate during pregnancy, stating that new data showed there was an increased risk of cleft lip and/or cleft palate (oral clefts) in children born to women treated with topiramate (Topamax and generic products) while they were pregnant.
Topiramate has also been linked to memory problems and mood changes, including depression and anxiety.
However, Gadde said 34 women became pregnant in Qnexa clinical trials and no birth defects were reported in their babies.
Plus, said Gadde, a pregnant woman would not be a candidate for Qnexa. He said “there is no reason for women to use weight loss drugs while they are pregnant or trying to become pregnant”.
Currently orlistat, available as a prescription drug in the US under the brand name Xenical and over the counter as Alli, is the only drug available for the long-term treatment of obesity.
Studies that pooled data from several trials show that participants taking maximum-strength orlistat can lose up to 7 pounds more weight than treatment with placebo after one year.
“The combination drug achieves about 19 pounds of weight loss relative to placebo at one year,” said Gadde who believes we don’t have enough options for treating obesity, as rates increase.
“Two thirds of Americans are overweight or obese,” said Gadde.
“For obese patients who have failed to achieve meaningful weight loss with diet and exercise, we have just one treatment before jumping to bariatric surgery. We need more treatment options,” he added.
For the 56-week phase 3 trial the researchers recruited 2,487 patients attending 93 centers in the US. To take part in the trial the patients had to have a BMI in the range 27 to 45 kg/m2 and two or more other conditions such as diabetes or heart disease.
The participants were randomly assigned to one of three groups: placebo, or one of two oral once-daily doses of the drug combination. All patients received diet and exercise advice.
Altogether, results were obtained for 2,448 patients, 979 who took the placebo, 488 who took the lower dose of the combination drug, and 981 who took the higher dose. The low dose comprised 7.5 milligrams of phentermine and 46 milligrams of topiramate, and the higher dose had 15 milligrams of phentermine and 92 milligrams of topiramate.
The low dose achieved an average of 7.8% weight loss over 12 months and the higher dose achieved 9.8% (both significant, p