Back to the Future: Repurposing Metformin, a Metabolically Active Drug, to Treat Mild-to-Moderate Ulcerative Colitis

The incidence of ulcerative colitis, an entity belonging to the inflammatory bowel diseases, is rising worldwide. Due to the unpredictable nature of its clinical flares and the need for chronic treatment, ulcerative colitis has a huge burden of psychological impairment and reduced quality of life. Although several treatments are available to manage patients with ulcerative colitis, their efficacy is unpredictable, and long-term remission is often difficult to achieve. Moreover, the more recent and expensive drugs are not easily available in many countries. These facts have prompted the research in this field to focus on finding additional treatments for such patients. Among the putative repurposing drugs, metformin, an oral antidiabetic agent used for over seventy years, seems to represent a good candidate. While randomized controlled trials suggest that metformin, as an adjunct to conventional treatments, may improve clinical outcomes in mild-to-moderate ulcerative colitis, population-based observational and genetic studies offer mixed signals regarding its role in long-term disease modification or primary prevention. This, together with the wide availability and the low cost of metformin, might represent a good example of repurposing, as detailed in the present review. However, human mechanistic validation remains limited, underscoring the need for further research.