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pioglitazone + metformin
- Development stage
- Unknown
- Lead developer
- University of Minnesota
- Modality
- Small Molecules
- Administration
- Oral
01
Overview
This combination therapy, consisting of the thiazolidinedione pioglitazone and the biguanide metformin, is being evaluated by the University of Minnesota in a Phase IIa clinical trial for the treatment of high-risk oral leukoplakia. Pioglitazone functions as a selective agonist for the peroxisome proliferator-activated receptor gamma (PPARγ), a nuclear receptor that regulates cell differentiation and apoptosis. Metformin activates AMP-activated protein kinase (AMPK) and inhibits mitochondrial complex I, leading to the suppression of the mTOR signaling pathway. By targeting these metabolic and proliferative pathways, the combination aims to reduce the grade and size of oral preneoplastic lesions, thereby preventing progression to oral squamous cell carcinoma. Both components are FDA-approved for type 2 diabetes but are being repurposed here for oral cancer prevention.
- Brand names
- Actoplus Met
- Other names
- Pioglitazone-Metformin combinationPioglitazone/Metformin
02
Targets
ND1 (Mitochondrial electron transport chain complex I)AMPK (Adenosine monophosphate–activated protein kinase)PPARG (Peroxisome proliferator-activated receptor gamma)
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