The Art and Science of Precision Medicine for Obesity

Editors note: after this post appeared, significant questions arose about errors in the Acosta paper described below. We will offer more information when more is available.

Update June 23, 2021: The journal has published a correction, making clear that this study was not randomized nor did it have a pre-registered protocol and leaving us with doubts about the study. For more, click here.

Precision medicine will transform healthcare. So say Francis Collins and Joshua Denny with a new commentary in Cell. It’s all about accounting for the individual in healthcare by accounting for differences in genes, environment, and lifestyles. In the new issue of Obesity, new research by Andres Acosta and colleagues from the Mayo Clinic demonstrate that precision medicine can bring considerable value to obesity care.

Targeting Anti-Obesity Medicines

This was a study of 450 persons with obesity. Acosta et al took validated measures of their body composition, resting energy expenditure, satiety, satiation, eating behavior, affect, and physical activity. From these data, they identified four different profiles – phenotypes. All but 15 percent of these subjects fit into one of those profiles. The groupings have straightforward labels: hungry brain, hungry gut, emotional hunger, and slow burn. However, some of the subjects – 27 percent – fit into more than one group.

After that, these researchers went on to test the clinical relevance of these groupings. In 312 patients, they conducted an RCT of treatment with anti-obesity medicines. One group received treatment targeted by their grouping. Treatment for the control group did not account for phenotypes.

The results were impressive. Patients in the targeted therapy group lost 75 percent more weight than those who didn’t. At the end of 12 months, the targeted group had lost 15.9 percent of their starting weight. But the control group lost only 9.0. To be clear, the result in the control group is a fairly typical outcome. The result for the targeted group is above and beyond what’s typical for currently available meds.

One Size Does Not Fit All

For anyone who has taken time to study obesity, this is not very surprising. What works for one person, seldom works for all. Bariatric surgery is a powerful tool. But even so, results do vary. The same is true for different dietary strategies. Now we see it in pharmacotherapy.

Kelly Brownell and Tom Wadden wrote about this 30 years ago, proposing a staged process for tailoring obesity care to the individual. Allison Field wrote about it in JAMA almost a decade ago, saying that one size does not fit all. Robert Kushner developed and validated a six-factor questionnaire for tailoring obesity care to the individual. In fact, he went so far as to translate this clinical tool into a book to guide patients in self-care.

All of this points to a future of precision medicine for obesity. Right now the art of it plays a big role because algorithms based on scientific evidence are still emerging. They need validation. So clinical judgment and also trial and error are part of the process.

But studies such as this new one from Acosta et al offer evidence of progress and promise for more to come.

Click here for the Acosta study and here for the commentary by Denny and Collins.

Street Light, painting by Giacomo Balla / WikiArt

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March 31, 2021