cox-2 inhibitor + metformin

This is a combination therapy consisting of a cyclooxygenase-2 (COX-2) inhibitor and metformin. COX-2 inhibitors are nonsteroidal anti-inflammatory drugs (NSAIDs) that selectively inhibit the cyclooxygenase-2 enzyme, reducing inflammation and pain, particularly in conditions like osteoarthritis (OA). Metformin is an oral antihyperglycemic agent widely used as first-line therapy for type 2 diabetes mellitus (T2DM), with additional anti-inflammatory and potential antineoplastic properties. The combination has been studied primarily in patients with OA and T2DM, where it was associated with lower rates of joint replacement surgery compared to COX-2 inhibitor monotherapy, possibly due to enhanced reduction of pro-inflammatory factors. Preclinical studies also suggest synergistic anticancer effects—such as inhibition of cell proliferation and tumor growth—when combining a COX-2 inhibitor like celecoxib with metformin, potentially through mechanisms involving mTOR pathway inhibition, increased p53 activity, apoptosis induction via caspases, suppression of PI3K-AKT signaling, and reduced migration/invasion in cancer cells[1][4][5].