Major Finding: In patients on the highest dose of phentermine plus controlled-release topiramate, systolic BP reductions were significantly lower than with placebo: 3.4 mm Hg after 28 weeks in EQUATE, 3.8 mm Hg after 56 weeks in EQUIP, and 3.2 mm Hg after 56 weeks in CONQUER.
Data Source: Pooled analysis of data on 3,985 patients in three clinical trials.
Disclosures: Dr. Oparil disclosed relationships with Vivus and numerous other pharmaceutical companies.
NEW YORK — An investigational weight-loss agent that combines two drugs slightly reduced blood pressure in an analysis of three large placebo-controlled clinical trials in a total of 3,985 patients.
The once-daily drug combines a low dose of the generic stimulant phentermine with a low-dose, controlled-release version of the antiepileptic topiramate. The two drugs have been shown previously to cause weight loss by different mechanisms, Dr. Suzanne Oparil said at the meeting.
Higher doses of phentermine are occasionally associated with increased BP, but the combined product appeared to produce enough weight loss—more than 10% of body weight after 56 weeks in two of the studies—to result in modestly lower BP, reported Dr. Oparil, professor of medicine, physiology, and biophysics and director of the vascular biology and hypertension program at the University of Alabama at Birmingham.
“We need a well-tolerated, safe, and effective weight-loss treatment,” said Dr. Oparil, who conducted the analysis as a consultant to Vivus, which is developing the combined agent under the brand name Qnexa.
But some physicians at the ASH meeting said they were not entirely convinced of the agent's safety. At the highest dose, a heart rate increase of about 1.5 beats per minute was observed.
The 56-week EQUIP trial enrolled 1,267 obese adults and compared the high-dose combination (phentermine 15 mg and topiramate 92 mg) and a low-dose combination (phentermine 3.75 mg and topiramate 23 mg) with placebo. The 28-week EQUATE trial enrolled 756 obese adults and compared the high-dose formulation and a mid-dose formulation (phentermine 7.5 mg and topiramate 46 mg) with placebo and with the respective single agents. The 56-week CONQUER trial enrolled 2,487 overweight and obese adults with two or more weight-related comorbidities and compared the high- and mid-dose combinations with placebo. Of the 4,510 patients who were initially enrolled in the three trials, 3,985 completed the studies.
In Dr. Oparil's pooled analysis of the three trials, the mean weight loss at week 28 was 1.9% of total body weight for the 1,579 patients on placebo, 5.1% for the 234 patients on the lowest dose of the drug, 8.0% for the 591 patients on the middle dose, and 9.9% for the 1,581 patients on the highest dose. All three active-treatment groups had significantly more weight loss than did the placebo group.
In the two trials that went to 56 weeks, CONQUER and EQUIP, weight loss reached 10.4% of body weight with the highest dose, significantly higher than the 1.5% with placebo.
The reductions in systolic BP in patients on the high-dose combination, compared with placebo, were 3.4 mm Hg after 28 weeks in EQUATE, 3.8 mm Hg after 56 weeks in EQUIP, and 3.2 mm Hg after 56 weeks in CONQUER; all three reductions were significant. Significant reductions in systolic BP also were seen with some of the lower doses of the combined product. For diastolic BP, only two of the higher-dose groups had significantly greater reductions than that seen with placebo.