Are we on our way to progressing beyond weight loss as the primary end point for judging the value of new medicines in obesity? On this closing day of Obesity Care Week, topline results for a promising new obesity medicine – petrelentide – prompts us to reflect on this question.

We suspect AI was making a subversive point when it came up with this headline for those topline results. Petrelentide is a promising new obesity medicine from Roche and Zealand. No, it did not cause people to lose more than 100% of their weight. Subversively or accidentally, though, this headline actually makes a point about the absurdity of chasing ever bigger numbers for weight loss. Beyond a certain point, more is not better.

The Distinction Is Tolerability

Amidst all the chatter about semaglutide and tirzepatide and which one delivers more weight loss, perhaps too many of us have lost sight of a basic fact about these drugs. They are tough to take. Weekly injections are not the end of the world, but the novelty wears off after a while. Having to refrigerate them is inconvenient. Needles can be off-putting. And then there are the side effects. People have to start low and go slow on these drugs so they won’t be puking their guts out. This is a clue that tolerability is a problem to be solved.

Petrelentide does not dispense with the needles or the refrigerator. But these topline results suggest that tolerability will be better. In fact, Zealand CEO Adam Steensberg called its tolerability “placebo-like.” And, yes, in this phase two study of 493 adults with overweight and obesity, the rate of discontinuation due to adverse effects was no different on the drug (4.8%) than it was on placebo (4.9%). This is good.

Judging by the weight loss outcome alone – 10.7% at 42 weeks – these are not stellar results. They are certainly good and with a drug that is more tolerable, it might indeed be good enough for a big commercial success. We will wait to see what happens in the next round of studies. But if people can get good enough weight loss with a drug that doesn’t make them sick, who wouldn’t choose that?

Beyond Tolerability

So yes, we are indeed ready for obesity medicines that have better tolerability. Especially when we start to think about long-term health outcomes. Because living longer and better with obesity under control requires us to keep taking our medicine. Obesity is a chronic disease.

And this means that new drugs have an opportunity to bring evidence that can help with long-term outcomes better than older drugs. This is why, for example, development of survodutide is so focused on preventing or reversing the progression of liver disease in people with obesity. MASH is just one of many chronic diseases that new and improved obesity medicines might prevent or reverse.

The opportunities for progress in obesity care really do not lie with an endless chase for bigger weight loss numbers. Future progress in obesity care will come more from gaining health than losing weight.

Click here for more on framing obesity care beyond weight loss, here, here, and here for more on the new toplines for petrelintide. For perspective on the limits to chasing more weight loss, click here.

The Great Sacrifice, painting by Nicholas Roerich / WikiArt