Comparison of Metformin Combinations with Other Repurposed Drugs in the Treatment of Hamster Fibrosarcoma: A Review

Background/Objectives: Metformin is a prominent candidate for cancer drug repurposing, backed by preclinical and epidemiological evidence showing reduced cancer incidence in diabetic patients. Its pleiotropic effects include AMPK activation, protein synthesis inhibition, and metabolic alterations. This review integrates global preclinical data via a comprehensive tabular overview alongside a cross-analysis of specific investigations of hamster fibrosarcoma. Since head-to-head comparisons of metformin-based combinations on hamster fibrosarcoma remain limited, this work performs an integrated cross-study evaluation to establish a clear comparative hierarchy of various repurposed adjuvants combined with metformin. Methods: A literature review and cross-study re-analysis of peer-reviewed preclinical studies were conducted, focusing on in vivo therapeutic outcomes within the BHK-21/C13-induced hamster fibrosarcoma model. Treatment regimens from distinct primary studies were evaluated side-by-side using tumor endpoint data expressed as a percentage of control mean (± SD). Only statistically significant pairwise differences (p < 0.05) determined the comparative hierarchy. Results: Integrated analysis identified disulfiram and diclofenac as the most promising adjuvants among compared metformin combinations, showing the highest statistical significance across all evaluated endpoints. The statistical ranking of the metformin-based combinations followed a descending order: disulfiram, diclofenac, nitroglycerin, itraconazole, and caffeine. Conclusions: By synthesizing previously fragmented primary data into a unified comparative framework, these findings provide a strong, consolidated preclinical rationale for metformin-based combination strategies. The established hierarchy of adjuvant potency resolves structural ambiguity and supports further translational and clinical investigation to evaluate their therapeutic potential in fibrosarcoma and other malignancies.