New FDA Guidance on Obesity Medicines: Unfortunately Stale

Drug development for obesity may well be in a golden age. In large part, this is because the scientific understanding of obesity has grown exponentially in the past two decades. Unfortunately, little or none of that is reflected in new draft guidance from FDA, issued yesterday for public comment, on developing the next generation of obesity medicines.

FDA seems to be stuck on outdated notions that treating obesity is all about weight loss, diet, and exercise. Medicines for obesity are simply “add-ons” to the gold standard of simple advice to eat less and move more. BMI is the primary measure of success.

There is good news here. This is only a draft. The agency is seeking input to improve it and this guidance really needs it.

“Obesity Is a Chronic Disease”

The last time FDA issued guidance on drug development for obesity was 2007. Needless to say, much has happened since then. Back then, the guidance did not even acknowledge that obesity is a disease. In fact, the guidance was only for “weight management products.”

It only took the agency 18 years, and now the guidance says it explicitly. “Obesity is a chronic disease characterized by excess adiposity.” But that is as far as they go.

These are still drugs for “weight reduction.” Not for obesity treatment.

Stuck in the Past on BMI

Because this is a simplistic framework for developing weight loss drugs, the agency seems stuck in the past, relying on BMI as the treatment target for clinical trials. Though the agency acknowledges “BMI has several limitations,” the guidance insists it “correlates strongly with total body fat in nonelderly adults.”

This is the fatal flaw of this stale framework. It defines meaningful outcomes as five percent or greater mean weight loss. Improvements in other signs and symptoms of obesity (e.g. sleep apnea, heart health, liver disease, diabetes) are merely “informative” secondary outcomes. This guidance is all about weight loss. These drugs are to be studied “as an add-on to standardized recommendations for diet and physical activity in all randomized subjects.”

And thus, the agency says, claims for these drugs “will generally be limited to weight reduction.”

A Draft Woefully Out of Date

Clearly, this guidance reflects a dated set of very low expectations for new obesity medicines. Five percent mean weight loss is a bit of a joke in the context of new drugs that deliver 20% or more. The health benefits of such modest weight loss are limited. New obesity medicines should aim to improve health, not just cause modest weight loss.

Fortunately, this is merely a draft. Public comments to FDA from smart clinicians and patient advocates can do much to help the agency give better guidance on new obesity medicines.

So please, click here to study the draft and look for the federal register posting to provide thoughtful comments when it opens up. For other reporting on this draft guidance, click here.

Waterfall Njommelsaska, chromolithograph by Carl Svante Hallbeck / Wikimedia Commons

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January 8, 2025