We have a flourishing market for new obesity drugs. But that market has a problem. New drug developers are stumbling over what to target with their drugs. The old way of looking at goals for new drugs in this space was to aim for greater weight loss. More is better – right? In a new editorial for the New England Journal of Medicine, Craig Hales points to a better way to think about this. We should be targeting better health with new obesity drugs.

Treat to Target Individually

Hales describes a better approach to obesity: treat to target. For other chronic diseases, like arthritis or diabetes, this is nothing new. But for folks stuck on weight loss as the singular goal for treating obesity, the concept is not so intuitive. Hales sums it up:

“A sustainable treat-to-target approach should extend to lifelong maintenance of health gains after initial weight loss. The intensity and composition of lifestyle interventions in the context of highly effective pharmacologic therapies also need further study. The pharmaceutical pipeline is promising, with potential improvements in safety (such as preservation of lean mass) and more convenience for patients (such as oral administration and monthly dosing). Greater effects on the health of Americans may be achieved not with antiobesity medications producing ever greater magnitudes of weight loss but with expanded access to safe and effective therapies for those who would most benefit.”

Caught in the Middle

What prompted the editorial by Hales was the clinical trial results for CagriSema. When these data emerged, the reception was lukewarm at best. Judged purely by weight loss, the numbers were nothing new or especially impressive. But Hales points out that if we are targeting better lifelong health, expanding the treat-to-target toolbox is certainly a good thing.

More recently, results of pivotal study results with orforglipron left investors cold. Not enough weight loss, thought many of them. But again, if the target is “lifelong maintenance of health gains” a solid option in the first daily oral tablet might meet a vast need.

In this light, the harsh judgments of CagriSema and orforglipron might have been premature.

The Real Challenge

The real challenge will be to fill out the story of long-term health gains beyond weight loss. Indications for cardiovascular risk reduction, sleep apnea, and liver disease are a start. There will be much more to come with other chronic diseases that come from untreated obesity.

In retrospect, weight loss will start to look like a side benefit. Health gains and longer, better lives will be much more meaningful. We are witnessing the start of a marathon.

Click here for the editorial by Hales and here for further perspective.

Bullseye Galaxy, LEDA 1313424, image from the Hubble Space Telescope / Wikimedia Commons