Therapeutic potential of metformin-based combination therapy in acute myeloid leukemia

Acute myeloid leukemia (AML) is the most prevalent form of acute leukemia. Despite great efforts, the overall prognosis for patients with AML remains poor, and the mortality rate due to relapse is also considerable. Consequently, the disease poses treatment challenges. Several studies have indicated that metformin may serve as a beneficial adjunct to traditional anti-leukemia medications, especially enhancing their effectiveness against drug resistance; however, it is not effective when used as a standalone treatment. In this context, combination therapies are currently being explored as a promising treatment option.

This study is a narrative review. A comprehensive literature search across multiple databases, including PubMed, Google Scholar, Scopus, Embase and Cochrane, yielded 103 relevant articles up to July 2024. From an initial total of 103 articles, we excluded unrelated and duplicate articles, as well as those for which the full text was unavailable and review articles. Ultimately, 32 articles were included in the study. During the database search, we employed search terms such as AML, combination, and metformin to find relevant articles.

According to the results of the studies, the combination of metformin with gilteritinib, sorafenib, 6-benzylthionosine, venetoclax, diclofenac, diflunisal, and cytarabine reduces intracellular ATP levels, inhibits glycolysis, halts the cell cycle, diminishes oxidative phosphorylation, increases the expression of anti-apoptotic proteins and increases cytotoxicity. This combination also induces apoptosis, reduces cell growth, and ultimately leads to a significant decrease in the burden of AML and an increase in overall survival for these patients.

Therefore, combining these drugs with metformin may enhance the synergistic effect and improve the treatment of AML patients.