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Experimental drug achieves unprecedented weight loss
Date:4/10/2011

-0.1%, -0.4%, -0.4%
  • Fasting insulin in pre-diabetics: 6.0pmol/L, -29.2pmol/L, -31.9pmol/LM

    The most common adverse events in the groups given placebo, phentermine 7.5mg plus topiramate 40mg, or phentermine 15mg plus topiramate 92mg, respectively were:

    • Dry mouth (2%, 13% and 21%)
    • parethesia (numbness or tingling), (2%, 14%, 21%)
    • constipation (6%, 15%, 17%)
    • insomnia (5%, 6%, 10%)
    • dizziness (3%, 7%, 10%
    • dysgeusia (distorted sense of taste) (1%, 7%, 10%)

    Depression-related events were found in 4 percent assigned to placebo, 4 percent assigned to phentermine 7.5mg plus topiramate 46mg and 7 percent to phentermine 15mg plus topiramate 92mg. Anxiety-related events were reported in 3 percent, 5 percent and 8 percent respectively.

    "Although the overall incidence of these events was relatively small," Gadde says, "clearly there is a dose-related increase in risk."

    The drug combination works in two ways, he says. Phentermine increases the release of norepinephrine, a brain chemical that may influence hunger and satiety. Topiramate has numerous mechanisms of action including effects on sodium channels, glutamate and GABA transmission, and carbonic anhydrase inhibition, although the mechanism responsible for weight loss is not clearly known.

    "We believe it mainly works by reducing hunger and increasing satiety, but may have an independent effect on glucose control," Gadde says. "More patients on placebo developed diabetes during one year than patients who were on the combination drug. More patients on the combination drug were also able to go off their diabetes and blood pressure medicines."

    Gadde believes more treatments are needed for obesity as rates increase. "Two thirds of Americans are overweight or obese. 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.
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  • Contact: Debbe Geiger
    debbe.geiger@duke.edu
    919-660-9461
    Duke University Medical Center
    Source:Eurekalert

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