Will Outstanding Results for Retatrutide Mark a Turning Point?
“I am over the moon about this,” said Harvard professor Caroline Apovian to us. She was talking about the outstanding topline results with retatrutide reported by Lilly from a phase three study. This is the so-called triple-G agonist that first stunned the world with its phase two results two years ago.
In the results yesterday, people lost an average of 29% of their starting weight at the highest of two doses tested. On the WOMAC pain scale assessment, joint pain went down by 75%. This was a 68-week study.
One of the most noteworthy aspects of this study is the number of patients – 18% at the highest dose – who withdrew from the study due to adverse events, including excessive weight loss. Lilly noted that these withdrawal rates were highly correlated with BMI at baseline. While 84% of patients had a BMI of 35 or greater at the beginning of the study, it was possible to enroll in it with a BMI as low as 27.
Apparently, those with a lower BMI were more likely to withdraw because of excessive weight loss.
A Turning Point?
The real question this prompts is all about turning a corner. Until now, researchers and investors have been chasing the goal of maximum weight loss. Health outcomes, while clearly important, have oddly been lurking in the background. Every new drug gets scrutinized for how much weight loss it produces.
When topline numbers for CagriSema weight loss were less than stunning, the Novo Nordisk stock price plummeted. But now we are reaching a point where it is now clear that more weight loss is not always better. It is hard to miss this point when patient withdrawals from the retatrutide study are partly due to excessive weight loss.
From Weight Loss to Weight Health
The second part of this story lies in the dramatic improvement in pain and physical function seen in this new study with retatrutide. Apovian described the focus on knee pain as brilliant:
“With highly effective obesity medicines, we already have great outcomes in preventing diabetes progression and heart disease. Now, with these data on improved knee pain and physical function, the picture becomes much clearer about health gains from treating obesity effectively.”
In short, we may be turning the corner from a blinding focus on weight loss to a more holistic focus on health gains. This has been a long time in coming.
Remember, though, these are just topline results. The whole story will emerge when we have a full presentation of the results and a peer-reviewed publication. On top of that, results of seven more studies of retatrutide in obesity and diabetes will be coming out next year.
We have a lot to anticipate and a lot to learn.
Click here for the announcement from Lilly, here, here, and here for further reporting.
The Corner, painting by Paul Nash / WikiArt
Subscribe by email to follow the accumulating evidence and observations that shape our view of health, obesity, and policy.
December 12, 2025
