# Pioglitazone

Pioglitazone is a diabetes drug (a thiazolidinedione) that makes your body more sensitive to insulin. It works by activating a receptor called PPARγ, which helps fat cells mature and soak up fat. That pulls fat out of places it should not be and improves whole-body insulin sensitivity. Activating PPARγ also dials down inflammatory genes and shifts macrophages toward an anti-inflammatory mode, which is why pioglitazone draws interest for age-related conditions beyond blood sugar. The IRIS trial (Kernan et al., 2016, NEJM) found it cut cardiovascular events in non-diabetics who had insulin resistance and a prior stroke or TIA. Nir Barzilai and colleagues have floated it in geroscience discussions as a candidate that hits metabolic and inflammatory hallmarks of aging. But the long-term safety concerns are real: heart failure, bone loss, and a possible link to bladder cancer. France and Germany suspended it in 2011 over safety signals. The EMA did not pull it EU-wide, but it added contraindications (active or past bladder cancer, unexplained blood in urine) and strict labeling, which limits its use as a longevity agent.

## Sources

- Kernan WN, Viscoli CM, Furie KL et al.. (2016). Pioglitazone after Ischemic Stroke or Transient Ischemic Attack (IRIS Trial). New England Journal of Medicine. https://doi.org/10.1056/NEJMoa1506930

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_Canonical: https://longevity-switzerland.com/en/glossary/pioglitazone · Part of Longevity Cities · Updated 2026-06-22_