Fibrosis-Modulating Effects of Metformin and Pirfenidone in Oral Submucous Fibrosis

"Metformin 500 mg is being tested for its potential role in treating oral submucous fibrosis (OSF) due to its antifibrotic and anti-inflammatory effects. This intervention will be administered orally at a dose of 500 mg twice daily (OD) for a specified 6 months treatment period for Group 2 .~Metformin activates AMPK (AMP-activated protein kinase), which inhibits TGF-β signaling and collagen deposition, reducing fibrosis and inflammation.~Distinction from Other Arms: Unlike Pirfenidone, which directly targets profibrotic cytokines, Metformin modulates metabolic pathways to exert antifibrotic effects. The Control Group will receive supportive care for OSF."

"Pirfenidone 200 mg (Pirfibet by Mactor Pharma, Pakistan) is an antifibrotic drug being tested for its potential role in treating oral submucous fibrosis (OSF). This intervention will be administered orally at a dose of 200 mg, twice daily for a specified treatment period which will be 6 months for Group 3 .~Pirfenidone modulates fibrotic pathways by inhibiting TGF-β and collagen synthesis, reducing fibrosis progression.~Distinction from Other Arms: Unlike Metformin, which has antifibrotic effects via AMPK activation, Pirfenidone specifically targets profibrotic cytokines. The Control Group will receive either a supportive care for OSF"

"The Supportive Care Group will receive Beclomethasone mouthwash (three times daily) and Vitamin E 400 mg (once daily) as part of supportive care for oral submucous fibrosis . This intervention serves as a comparison group to evaluate the efficacy of Metformin and Pirfenidone.~Beclomethasone is a topical corticosteroid that reduces inflammation and provides symptomatic relief in OSF.~Vitamin E is an antioxidant that may help reduce oxidative stress and improve tissue healing.~Distinction from Other Arms:~Unlike Pirfenidone and Metformin, which target fibrosis at the molecular level, Beclomethasone + Vitamin E primarily focus on symptom relief.~This arm will serve as an active comparator to determine whether the antifibrotic effects of Metformin and Pirfenidone provide superior therapeutic benefits."