Pakistani study highlights metformin's potential against Oral Submucous Fibrosis

KARACHI: A team of researchers from Ziauddin University has published a high-impact systematic review suggesting that metformin, a widely prescribed medication for type 2 diabetes, could emerge as a promising future therapeutic option for Oral Submucous Fibrosis (OSF), a debilitating oral disease that affects millions across South Asia.

The review, published in the internationally renowned Pharmacological Research journal (Clarivate Q1, Impact Factor 12.2), was led by Prof. Dr. Afifa Razi, Professor and Head of the Department of Oral Medicine and Diagnosis at Ziauddin College of Dentistry, in collaboration with Dr. Shumaila Usman, Associate Professor at the College of Molecular Medicine, Ziauddin University, and an interdisciplinary research team.

Oral Submucous Fibrosis is a chronic, progressive and potentially malignant disorder strongly associated with areca nut consumption, including gutka, supari and paan. The disease causes progressive scarring and stiffening of the oral tissues, resulting in restricted mouth opening, burning sensations, difficulty eating and speaking, and an increased risk of oral cancer. It remains a significant public health challenge in Pakistan, India and other South Asian countries.

Current treatment approaches largely focus on relieving symptoms and slowing disease progression, with no established therapy capable of reversing the underlying fibrotic process. This has prompted growing interest among researchers in identifying existing medicines that could be repurposed for treating the condition.

To assess the available evidence, the Ziauddin University team conducted a systematic review, critically evaluating published preclinical and clinical studies investigating the antifibrotic properties of metformin. The review included 29 eligible studies comprising laboratory experiments, animal research, combined experimental studies, randomized clinical trials and observational studies.

According to the researchers, the collective evidence indicates that metformin consistently demonstrated antifibrotic effects through several biological mechanisms. These included activation of AMP-activated protein kinase (AMPK), inhibition of the transforming growth factor-beta (TGF-β)/Smad signalling pathway, suppression of inflammatory cytokines, reduction of oxidative stress and regulation of extracellular matrix deposition—all of which play important roles in the development and progression of fibrosis.

Based on these findings, the researchers suggest that metformin represents a scientifically plausible candidate for future investigation as a treatment for Oral Submucous Fibrosis.

However, the authors emphasize that the review does not establish metformin as a proven treatment for the disease. Instead, it provides an evidence-based foundation supporting the need for larger, well-designed clinical trials to determine whether the drug can safely and effectively benefit patients with OSF before it can be recommended for routine clinical use.

Beyond its clinical implications, the publication marks a notable achievement for Pakistan's dental research community. Appearing in one of the world's leading pharmacology journals, the study highlights the growing contribution of Pakistani researchers to internationally recognized oral health research and the expanding field of drug repurposing, which explores new therapeutic uses for existing medicines.

Researchers say the findings could help guide future translational studies aimed at developing more effective treatment strategies for Oral Submucous Fibrosis and other fibrotic disorders, while reinforcing the importance of continued scientific collaboration in addressing diseases that disproportionately affect populations in South Asia.