The MET-PREVENT trial enrolled over 1,000 participants to test whether metformin could delay onset of cardiovascular disease, cancer, dementia, and other age-related conditions in healthy adults. After following subjects for several years, researchers found no significant reduction in disease incidence compared to placebo groups. This represents a significant setback for the diabetes drug that has been widely touted in longevity circles as a potential anti-aging intervention. The null findings challenge the extrapolation of metformin's benefits from diabetic populations to healthy aging adults. While laboratory studies have shown metformin activates AMPK pathways and may influence cellular aging mechanisms, these molecular effects apparently don't translate into measurable disease prevention in real-world populations. The trial's design focused on hard clinical endpoints rather than biomarkers, providing robust but disappointing evidence. This outcome underscores the substantial gap between promising preclinical aging research and actual human health outcomes. For longevity enthusiasts who have embraced off-label metformin use, these results suggest the intervention may not deliver the broad protective effects many hoped for. The findings also highlight how aging research requires extremely large, long-term studies to detect meaningful differences in disease onset.