A cross-sectional analysis found that approximately one-third of U.S. adults without diabetes who qualified for novel weight loss medications were excluded from the pivotal clinical trials that established their safety and effectiveness.

In the research letter, published in JAMA Internal Medicine, investigators examined trial generalizability for three medications: glucagon-like peptide (GLP)-1 receptor agonists liraglutide and semaglutide, and the dual GLP-1/GIP receptor agonist tirzepatide.

Analysis of National Health and Nutrition Examination Survey data showed that among U.S. adults meeting U.S. Food and Drug Administration label criteria, 28.1% would have been excluded from liraglutide trials, 26.2% from semaglutide trials, and 33.1% from tirzepatide trials.

The data, collected from 2013 to March 2020, represented 110.3 million U.S. adults with overweight or obesity. The most common exclusion criteria were:

• Major depressive disorder (17%)
• Malignant neoplasms (7.6%)
• Liver disease (6.1%, tirzepatide only)
• Uncontrolled hypertension (3.6% to 3.7%).

The analysis revealed that 23.5% of adults eligible for tirzepatide were taking medications that could slow gastrointestinal motility. Adults aged 60 years or older were more likely to meet exclusion criteria compared with younger age groups.

Research limitations included self-reported medical conditions and the inability to measure all trial exclusion criteria with accurate temporality.

The analysis was supported by grants from the National Institute on Aging and the National Institutes of Health Medical Scientist Training Program.

One author reported receiving grants from the National Institute on Aging during the conduct of the study and grants from the American Heart Association outside the submitted work. No other disclosures were reported.