Cana/Phen: Unlocking a Potential New Drug Combination

A new study in Diabetes Care provides tantalizing new data on a potential new combination drug for obesity: cana/phen. The study compared a combination of 300 mg of canagliflozin and 15 mg phentermine to each drug alone and to placebo. It was a randomized, controlled study that lasted 26 weeks. The combination was more effective than either drug alone and placebo.

The combination produced a weight loss of 7.5% of baseline weight over this six-month study.

Combining Two Well-Known Drugs

Canagliflozin, under the brand name Invokana, is a blockbuster drug for diabetes. With 2016 sales of $1.4 billion, it’s the leading drug in a class known as SGLT-2 inhibitors. These drugs work in diabetes by causing people to excrete a little extra glucose in their urine.

By excreting that extra glucose, people are dumping extra calories, which leads to modest weight loss. But dumping those calories causes a little bump in appetite. That’s why the weight loss is modest – only about 2% – with canagliflozin and other SGLT-2 drugs. People naturally eat just a bit more to offset the loss of calories.

So combining phentermine with canagliflozin makes sense. It’s a well-known suppressant for appetite that’s older than dirt. It’s only indicated for short-term use, because back in 1959 that’s how doctors treated obesity. They did not understand that short-term obesity treatment made no more sense than short term diabetes treatment. The problem comes right back when the treatment stops.

What Next?

This study proves that the combination works and is reasonably safe in the short term. But it’s not good enough to get the combination approved by FDA. For that, J&J would have to do longer term studies to show sustained efficacy and safety.

And especially since phentermine causes a little increase in heart rate, it would need a cardiovascular outcomes study. Such a study carries a big price tag in the hundreds of millions of dollars.

Only time will tell if J&J will invest in an obesity indication for this combination.

Meanwhile, a key competitor in diabetes – Novo Nordisk – is carving out a competitive advantage with its work in obesity. Liraglutide (Saxenda) has become the most successful of a new generation of obesity drugs. The company is investing is at least five other new drugs in development for obesity.

Perhaps success will breed competition to provide better options for people living with the complex, chronic disease of obesity.

Click here for the Cana/Phen study in Diabetes Care and here for more from Healio.

Combination, photograph © Charles Dyer / flickr

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March 30, 2017