Research presented at a recent Food and Drug Administration (FDA) workshop indicates the need for more comprehensive testing of new medications in people with obesity. These data suggest that drugs might not reach effective levels in people with obesity or might remain in the body longer than expected due to altered drug distribution and different metabolic processes in the body.
In the United States, nearly 42% of adults have obesity. Both overweight and obesity are significantly associated with a wide range of comorbid health conditions, including type 2 diabetes, cancer, heart disease, and certain psychological disorders like depression. Many of the comorbidities associated with obesity require pharmacological treatment to address their health concerns. Research has indicated that there are differences in how the body processes and responds to drugs in people with obesity.
For example, when a highly lipophilic (fat soluble) drug is prescribed to a person living with obesity, they will metabolize the medication differently than someone without obesity due to increased body fat. The amount of fat tissue in a person’s body increases the distribution space and thereby lowers the serum concentrations of fat soluble medications, which can in turn affect the effectiveness of the drug. These characteristics result in a longer half-life compared to the half-life of these drugs in people without excess body fat. Furthermore, the drug will continue to be released from fat tissue after the medications are stopped, leading to prolonged exposure to the medication than might otherwise be expected.
Fat soluble medications are often used in care for people with obesity with comorbid conditions such as hypertension, schizophrenia, or depression. Due to the altered metabolism of these medications, people with obesity can be either underdosed or overdosed when prescribed a standard drug regimen. For example, diazepam, an antianxiety and antiseizure medication, was found to have a longer half-life in people with obesity, leading to a delay in achieving the maximal drug effect. The medication also persists in the body for longer periods of time after being discontinued in patients with obesity. The health implications of the altered metabolism of drugs in people with obesity emphasize the need for medications to be tested and studied in this group of patients to ensure that they receive an appropriate dose.
Obesity advocates have begun to realize the significance of this problem and are advocating for the FDA to include patients with obesity in new drug trials. Patients with obesity may be underrepresented in drug trials for medications that will be commonly prescribed to patients with obesity. In November of last year, experts from the University of Maryland Center of Excellence in Regulatory Science and the FDA held a workshop on this topic. Experts at the workshop did not come to a consensus on whether patients with obesity should be considered a specific population in drug development trials, but agreed that modeling tools should be used to assist in medication dosing for patients with obesity.
To ensure the safety of medications for patients with obesity, the FDA and drug developers should take a number of steps. The FDA should require a sufficient number of patients with obesity be included in clinical trials to identify how differences in obesity classes affect the effective dosage of the drug. In addition, information should be included in the descriptions of medication use to warn patients with obesity about the differential effects of medications. If that information is not available, there should be a warning that fat soluble drugs have not been adequately tested in a representative group of individuals with obesity in the clinical trials of the drug.
We gratefully acknowledge Ted Kyle for his contribution to this month’s newsletter.