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**Sotorasib + metformin** is an unbranded combination of two small molecule drugs: sotorasib, a selective and irreversible inhibitor of KRAS G12C-mutated protein, and metformin, a biguanide oral antihyperglycemic primarily used in type 2 diabetes. This combination is not a fixed-dose product but has been studied as a coadministered therapy. Preclinical and early phase clinical data indicate that the combination exerts synergistic cytotoxic and pro-apoptotic effects in various lung cancer cell lines. Sotorasib inhibits the MAPK signaling cascade by targeting KRAS G12C, while metformin acts to inhibit the AKT-mTOR-P70S6K pathway, a known mechanism of resistance to KRAS inhibitors. Together, these drugs result in enhanced blockade of cell proliferation and survival pathways, especially in cancers with KRAS mutations. Both drugs are orally bioavailable and have established safety profiles when used individually; coadministration in healthy subjects was well tolerated and did not significantly change the pharmacokinetics or pharmacodynamics of either agent[1][2][3][4][5].
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