Article Impact Level: HIGH Data Quality: STRONG Summary of JAMA Internal Medicine. https://doi.org/10.1001/jamainternmed.2024.6340 Lily G. Bessette et al.
Points
- A large proportion of U.S. adults with overweight or obesity meet FDA criteria for weight-loss medications like liraglutide (88.9%), semaglutide (89.0%), and tirzepatide (90.6%).
- Between 26.2% and 33.1% of eligible individuals met exclusion criteria from clinical trials, such as major depressive disorder, malignancies, liver disease (for tirzepatide), and uncontrolled hypertension.
- Adults aged 60 and older were more likely to meet exclusion criteria compared to younger populations, limiting the applicability of trial findings to this demographic.
- The study underscores a disconnect between clinical trial populations and those eligible for these treatments, raising concerns about real-world applicability.
- The authors recommend postmarketing studies and updated FDA labeling to caution against using these medications in populations excluded from clinical trials until more evidence becomes available.
Summary
A recent cross-sectional study assessed the extent to which individuals meeting the U.S. Food and Drug Administration (FDA) criteria for glucagon-like peptide 1 (GLP-1) receptor agonists (liraglutide, semaglutide) and GLP-1/glucose-dependent insulinotropic polypeptide (GIP) receptor agonist (tirzepatide) for weight loss also met the exclusion criteria of pivotal clinical trials for these treatments. Using pooled data from the National Health and Nutrition Examination Survey, the study analyzed 8,767 participants representing 110.3 million U.S. adults with overweight or obesity. The study found that a significant proportion of individuals eligible for treatment based on FDA guidelines would have been excluded from clinical trials.
The analysis revealed that 88.9% of participants met the FDA criteria for liraglutide, 89.0% for semaglutide, and 90.6% for tirzepatide. However, a substantial portion of these participants—28.1% for liraglutide, 26.2% for semaglutide, and 33.1% for tirzepatide—met at least one of the exclusion criteria. Standard exclusions included major depressive disorder, malignancies, liver disease (for tirzepatide), and uncontrolled hypertension, with adults aged 60 years or older being more likely to meet these criteria than younger adults.
These findings highlight a gap in the generalizability of clinical trial data to the broader population that could benefit from GLP-1 and GLP-1/GIP receptor agonists. The study suggests that, until further evidence is gathered from postmarketing studies, the FDA should consider updating its labeling to advise caution regarding using these medications in populations excluded from clinical trials.
Link to the article: https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2826335
References Bessette, L. G., & Anderson, T. S. (2024). Generalizability of clinical trials of novel weight loss medications to the us adult population. JAMA Internal Medicine. https://doi.org/10.1001/jamainternmed.2024.6340
