metformin + dextromethorphan

Metformin + dextromethorphan is a combination of two FDA-approved small molecule drugs. Metformin is an oral biguanide antidiabetic agent primarily used to treat type 2 diabetes mellitus by improving glucose tolerance, lowering both basal and postprandial plasma glucose, decreasing hepatic glucose production, and increasing insulin sensitivity. Dextromethorphan is a cough suppressant that acts as a non-competitive NMDA receptor antagonist and sigma-1 receptor agonist, commonly used for symptomatic relief of cough. Recent preclinical research suggests that the combination of metformin and dextromethorphan may have synergistic effects in inhibiting nicotine-enhanced cancer-initiating cell properties and esophageal squamous cell carcinoma (ESCC) progression by targeting the cholinergic receptor nicotinic alpha 7 subunit (CHRNA7) pathway—dextromethorphan inhibits nicotine binding to CHRNA7 while metformin downregulates CHRNA7 expression via epigenetic modulation[2]. This combination has been proposed as a potential preventive or therapeutic strategy against nicotine-promoted ESCC and possibly other nicotine-sensitive cancers[2].