April 11th, 2011
Phentermine-Topiramate Combination Yields Significant Weight Loss
Larry Husten, PHD
The experimental diet drug combination of phentermine and topiramate demonstrated “robust efficacy” in CONQUER, a large new trial published online in the Lancet. The trial’s results come after a year in which the FDA turned down three investigational diet drugs (including Qnexa, the phentermine-topiramate combination used here) and removed the diet drug sibutramine from the market, leaving only one diet drug, orlistat, on the market.
Kishore Gadde and colleagues randomized 2,487 overweight or obese patients who had at least two comorbidities to placebo or a high- or low-dose combination of phentermine and topiramate for 56 weeks.
At 56 weeks, weight loss was
- 1·4 kg in the placebo group;
- 8·1 kg in the low-dose combination group (p<0.0001);
- 10·2 kg in the high-dose combination group (p<0.0001).
At least 5% weight loss was reached by:
- 21% of patients in the placebo group;
- 62% of patients in the low-dose group (p<0·0001);
- 70% of patients in the high-dose group (p<0·0001).
The investigators also report improvements in blood pressure, lipids, glucose control, and inflammatory markers.
The most common side effects associated with the experimental combination were dry mouth and paraesthesia. The investigators conclude that the side effects either were tolerable (e.g., taste disturbance) or could be managed by discontinuing the drug (nephrolithiasis, metabolic acidosis, and cognitive and psychiatric adverse events).
The authors write that the drug combination “could be a valuable addition to the small arsenal of effective obesity treatments that are available to family doctors.”
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I just want to point out an important caveat to this news story (which I probably should have realized when I wrote it!):
The data in this study are not entirely new. Although unpublished until now, the data from this trial WAS considered by the FDA advisory committee last year. Here’s an excellent news report from the LA Times that puts the study in context:
latimes.com/health/boostershots/diet-weight/la-heb-diet-drug-20110410,0,2767450.story
When FDA staff looked at the data from this trial along with a second trial, they concluded that the difference between Qnexa and placebo was “of nominal statistical significance.”
So the message is to beware the hype. The Lancet press release and numerous news stories have already touted this study as a potential turnaround for the drug. Let’s see what happens.
The FDA needs to take a second look.Both drugs have been effective in promoting weight loss in many patients but must be combined with a significant change in life style to include diet choices and an appropiate exercise program.The FDA could provide some leadership in this area.Sustained weight loss medically supervised can be therapeutic in a number of diseases especially if combined with an appropiate exercise program.
Competing interests pertaining specifically to this post, comment, or both:
none
According to the LA times article mentioned by Larry, the Lancet study was funded by Vivus, 3 of its 7 authors are Vivus employees, another was an employee of the CRO that coordinated the study for Vivus, the lead author has served as a Vivus consultant, and the 2nd author acknowledged receiving donations, honoraria, consulting fees or grants from Vivus. Does this cast a shadow on the study?