Progress on a New Combination for Obesity Treatment

Canagliflozin-Phentermine Phase II EfficacyLate-breaking data presented this past weekend at the Scientific Sessions of the American Diabetes Association provides a good look at the efficacy of a new combination drug treatment for obesity. The combination is 300 mg of canagliflozin (Invokana) and 15 mg of phentermine.

The combination of these two drugs produced an average weight loss of 7.5% of body weight after six months – efficacy in a range that may meet FDA approval criteria for new obesity medications. The phase II study was a randomized, controlled comparison of the combination to each of the individual drugs and to placebo. The combination was significantly better than placebo (0.6% weight loss) or either of the individual drugs in the combination.

The combination also produced a significant decrease in blood pressure and an increase in heart rate, largely attributable to the phentermine.

Canagliflozin is an SGLT2 inhibitor used to treat type 2 diabetes. It works to promote excretion of glucose from the blood. In addition to helping with diabetes, excreting glucose has the effect of helping the body shed calories and thus promoting weight loss with a shift in energy balance.

One reason that weight loss with canagliflozin alone is so modest (1.9% after six months) is that the shift in energy balance it causes can also lead to increased hunger and increased food intake. In this new combination, phentermine serves the purpose of offsetting that increased hunger. So the combination of these two drugs works better than either of them by themselves.

It’s noteworthy that these results were released without a great deal of hype about a new breakthrough for weight loss. Larger scale phase III studies with this new combination would be necessary before it could be submitted to FDA for approval. As everyone who has tried to innovate in obesity care has learned, it’s a long, hard slog to gain acceptance for innovations in obesity. Progress is coming, but it’s taking time.

This new combination could become a significant part of that progress.

Click here for the research abstract and here for a report from FiercePharma. Click here for more on the effects of canagliflozin on body composition and here for more on its effect on appetite.

Combo, photograph © Javier Morales / flickr

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June 13, 2016