Learning That Obesity Treatment Is a Marathon, Not a Sprint
This is a painful lesson and most of the world is very slow to take it to heart. Dealing with obesity – on almost every level – is a marathon, not a sprint.
Today’s lesson is about orforglipron, an oral GLP-1 agonist in development by Lilly. This drug is a small molecule that can be produced in volume at costs believed to be much lower than the cost of producing the elaborate peptide molecules of semaglutide, tirzepatide, and a host of other peptides in development. Understandably, some people have a lot of enthusiasm for this new drug, which will be going to FDA for approval next year.
Yesterday, the company announced topline results from a pivotal phase 3 study with orforglipron. People taking the highest dose of this tablet (36 mg) lost 12% of their starting weight after 72 weeks. These are “modest results,” say most of the headlines.
Lilly’s stock price promptly took a nosedive, dropping by 14%. Ouch.
Investors wanted to see bigger numbers for short-term weight loss.
But Lilly Likes These Results
Lilly CEO David Ricks told financial reporters that he likes these results. He believes that the short-term weight loss is “in the range” of what will satisfy many people. More importantly, he sees this news as delivering on strategic objectives for orforglipron:
“The goal was to create an oral pill that was convenient and can be made at a huge scale, really, for the mass market, and had weight loss that was competitive with other single-acting GLP-1s, and that’s what we’ve achieved,”
Refocusing on the Marathon
Make no mistake. There is a big disconnect here. The world is very slow to come around to the understanding that obesity is a complex, chronic disease. Yes, more people are coming around to that view. This is something that recent survey research confirms. But still, most people have not come around yet.
Instead, most people think in terms of short-term weight loss rather than long-term obesity treatment. They think about it more like they would about treating an infection. “Did we clear it up?”
This is not at all how we think about other chronic conditions like diabetes or high blood pressure. We cannot imagine someone thinking that the only thing that matters with new medicines for hypertension is producing bigger and bigger drops in blood pressure. That would simply make no sense.
Even health professionals seem uncomfortable with thinking in terms of chronic care and long-term outcomes for the chronic disease of obesity. More than once at a recent conference, we heard professionals express doubts about long-term therapy for obesity. Having to keep taking these medicines is a big drawback, they say.
The implicit bias is that this is an acute problem. Weight loss should resolve it. They might not come right out and say it. But this mental frame seems rather entrenched.
Gaining Health
Archaic perspectives with a fixation on weight loss are changing, albeit slowly. As the evidence builds for long-term health outcomes with ongoing obesity treatment, more people are seeing the importance of focusing on health more than weight. It is frustratingly slow movement, but progress nonetheless.
Will orforglipron be a home run for Lilly? Maybe.
Its success will depend upon whether it reaches that mass audience Lilly anticipates and whether it delivers on long-term health improvements. We shall see.
Click here, here, and here for more on these topline results with orforglipron. For more on the challenge of helping people re-think obesity, click here.
Azmeraw Bekele Molalign, Paris Half Marathon 2014, photograph by Pierre-Selim Huard, licensed under CC BY 3.0
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August 8, 2025
