This past January the FDA published a draft guidance entitled “Obesity and Overweight: Developing Drugs and Biological Products for Weight Reduction.” The draft updates a 2007 guidance. For the drug to be recognized as effective, the new guidance proposes that a new obesity drug has to demonstrate at least a 5% decrease in body weight compared to the control group after 1 year of drug treatment.
The new guidance differs from the old guidance and now officially refers to obesity as a “chronic disease,” instead of a “chronic, relapsing health risk”. This new stance shows a growing recognition of obesity as a disease and considers treatment as a multifaceted approach.
The draft also shifts from its previous statement in the 2007 guidance of “the use of a weight-management product should be contemplated only after a sufficient trial of lifestyle modification has failed” to a new stance of combining these approaches. The new draft states “the lifestyle-modification programs used in the preapproval trials should be applicable to patients who would be prescribed the drug after approval. At least one phase 3 trial should incorporate a standard-of-care diet and physical activity program.”
As we have said, the impacts of obesity as a chronic disease go beyond just the weight of a patient. There is no “weight requirement” to define obesity; recent conversations in the obesity advocacy community as well as the recent Lancet Commission publication, have been working towards a standard diagnosis, which continues to be debated.
If this updated guidance recognizing obesity as a chronic disease is approved, it could encourage earlier and more effective treatment options for patients. Patients won’t have to attempt and fail lifestyle modifications before being considered for medication. Instead, the guidance allows for an earlier integration of obesity medications and treatment. The new proposed guidance could also further promote biases in obesity diagnosis and treatment. For example, the heavy emphasis on weight loss and lifestyle-modification can reinforce the biased view that obesity is only a matter of lifestyle and behavioral choices rather than a complex, multifaceted disease.
Because many pharmaceutical companies already manufacture GLP-1 drugs with a greater than 5% weight reduction, this guidance will not significantly change their approach. The new requirement to integrate lifestyle interventions into clinical trials may add a useful layer of complexity to the approval process. Because many existing companies already meet the weight-loss benchmarks, manufacturers may shift their focus to address the FDA concern about the long-term safety of the drugs.
The FDA guidance also addressed the need to assess the loss of fat and lean tissue. All significant weight losses reflect a combination of fat and lean tissue loss. What is not clear is how much loss of lean tissue is too much.
The FDA will also need to set a clear definition of success in obesity treatment. Setting weight loss as the standard for success does not address other potential measures of success, such as improved metabolic markers (blood sugar, cholesterol), lifestyle, mental health, and activities of daily living. The FDA will continue to be taking comments on the draft guidance until April 8, 2025 here.