$38 Million Federal Trial to Test Whether Rapamycin, Semaglutide, and Dapagliflozin Can Slow Aging in Healthy Adults
The biology of aging is understood far better than it was fifty years ago. Dozens of genetic and pharmacological interventions extend healthy lifespan in rodents. Rapamycin, which targets the mTOR pathway, delays multiple age-related conditions in mice and is the most replicated longevity intervention in the NIA's Interventions Testing Program. Metformin, the diabetes drug, correlates with reduced age-related disease incidence in epidemiological data. Semaglutide, a GLP-1 receptor agonist originally developed for diabetes and obesity, has shown effects on cardiovascular and metabolic health that extend well beyond weight reduction.
None of these drugs has been tested in a rigorous, large-scale clinical trial specifically designed to determine whether they slow age-related functional decline in otherwise healthy older adults. The VITAL-H trial, now funded with up to $38 million from the Advanced Research Projects Agency for Health (ARPA-H), is built to fill that gap.
What the trial is designed to test
The Validation and Intervention Testing for Aging, Longevity and Healthspan (VITAL-H) trial will enroll healthy adults aged 60 to 65 - chosen because this window represents a point where functional decline becomes measurable but disease burden remains relatively low. The trial will study three FDA-approved medications: rapamycin, dapagliflozin (an SGLT2 inhibitor used in diabetes and heart failure), and semaglutide.
All three are orally administered and have established safety profiles from years of post-marketing surveillance, allowing their use in healthy individuals without the risk profile of experimental compounds. Each targets different biological pathways associated with aging: rapamycin affects cellular senescence and nutrient sensing through mTOR inhibition; dapagliflozin influences metabolic and cardiovascular function; semaglutide affects energy metabolism, inflammation, and cardiovascular risk.
"Over the past 50 years, global life expectancy has increased substantially, yet the age of onset of age-related diseases and disabilities has remained largely unchanged," said Dr. Elena Volpi, director of the Barshop Institute and lead investigator of VITAL-H. "Our population is living longer but with declining function, increased disability and reduced quality of life with major implications for healthcare utilization, caregiver burden and societal costs."
Measuring what matters: Intrinsic Capacity
One of the trial's methodological commitments is the large-scale validation of Intrinsic Capacity, a concept developed by the World Health Organization to assess healthy aging by measuring a person's physical and mental reserve rather than simply counting diagnoses. Intrinsic Capacity is evaluated across five domains: cognition, locomotion (mobility), psychological wellbeing, vitality (including energy and nutrition), and sensory function.
Previous clinical trials targeting aging have been criticized for relying on disease diagnosis as the primary endpoint - a measure that requires waiting until something goes wrong before the trial can show an effect. Intrinsic Capacity endpoints detect functional change earlier and more continuously, which is essential for trials in healthy populations where the timeline to disease onset may exceed any feasible study period.
Participants will be monitored with wearable devices throughout the trial, generating continuous data on activity, sleep, and physiological parameters. This approach supplements clinic-based assessments with real-world functional data and should improve the sensitivity of the primary endpoints.
VITAL-H within ARPA-H's PROSPR program
VITAL-H is integrated into ARPA-H's Proactive Solutions for Prolonging Resilience (PROSPR) program, which is designed to identify biochemical and physiological markers of aging and develop interventions that maintain function during the aging process. "PROSPR is designed to identify therapeutics that show the aging process is not an inevitable slide into disability," said Andrew Brack, ARPA-H program manager. "VITAL-H will help show whether we can preserve everyday abilities during a critical window of midlife aging."
The trial will recruit participants primarily from South Texas, a region whose demographics - including a large Hispanic population and significant economic diversity - closely mirror the projected composition of the U.S. population over the coming decades. That geographic choice is deliberate: a trial on aging that produces results generalizable only to affluent white populations has limited public health value as the U.S. population ages and diversifies.
The Barshop Institute's track record
The award positions UT San Antonio's Barshop Institute as the national anchor for VITAL-H, building on its existing designations as an NIA-funded Nathan Shock Center, Claude D. Pepper Center, and Population Aging and Social Studies Center, as well as its role as a lead site in the NIA's Interventions Testing Program - the multi-site study that has systematically tested rapamycin and other compounds in aging mice over the past two decades. The Institute will coordinate with San Antonio's Geriatric Research and Clinical Center, the South Texas Veterans Health Care System, the Texas Diabetes Institute, and a mobile research clinic to reach the full trial population.
The contract is structured as "up to $38 million" - a performance-based structure common in ARPA-H awards that ties full funding to milestone achievement rather than guaranteeing the entire amount at the outset.