Another Combination Drug for Obesity in the Works

Some years ago, Louis Aronne predicted that combination drug therapy would be the future of obesity medicine. It’s looking more and more like he was right.

An early look at another combination drug for obesity — lorcaserin + phentermine — came with the late-breaking posters on Thursday at ObesityWeek 2014. Steven Smith and colleagues presented results from a phase II study with this combination. It’s tough to conclude too much from a research meeting presentation of a drug that is this early in development. But it is pretty clear that the combo met the goals for its primary endpoint in this study: safety.

They tested lorcaserin 10 mg twice a day versus a combination with phentermine 15 mg. For the combination, they tested two different ways of taking it — once or twice daily. The study was designed to look for any signal that the combination would create a safety problem with serotonin receptors. That was the kind of problem that sank the combination of dexfenfluramine and phentermine 18 years ago.

The results were reassuringly boring. The primary endpoint was a comparison of the proportion of adverse effects related to serotonin. Success was defined as seeing no more of these effects in the combination than with either of the drugs alone. And that’s exactly what they saw — slightly but not significantly higher rates of serotonergic adverse effects.

The secondary endpoints were more interesting. Efficacy was improved with the combination. Percent weight loss with lorcaserin alone versus the combination once or twice daily was 3.8%, 7.3%, and 8.7% respectively. Heart rate was slightly increased in the patients receiving the combination twice daily, but not in those receiving it once daily. Fewer people (2.6%) discontinued the once-daily combination due to adverse effects than either the twice-daily combination (10.1%) or the twice daily dosing of lorcaserin alone (5.1%).

The lower discontinuation rate in the once-daily combination is especially interesting.

All of this points to the possibility of a once-daily combination drug that works better than lorcaserin alone. But it’s just that — a possibility. Much work will be needed to see if these observations hold up in larger studies. And you can be sure that cardiovascular safety will examined in microscopic detail.

Already, we have two combination drugs for obesity: phentermine/topirimate and naltrexone/bupropion. We may have a third on the way.

Click here for the abstract and here for more from MedPage Today.

Two Handed, photograph © Darwin Bell / flickr

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