Potential of Diabetes Medication Metformin in Preventing Leukemia Unveiled in Mouse Study

Recent research conducted by scientists at the University of Cambridge suggests that the well-known and affordable diabetes drug, metformin, could play a role in preventing a type of blood cancer called acute myeloid leukemia (AML). The study, carried out on mice, indicates that metformin might help stop pre-cancerous blood cells from progressing into full-blown leukemia, especially in individuals at high risk due to specific genetic mutations.

Every year, around 3,100 people in the UK are diagnosed with AML, an aggressive form of blood cancer that is particularly challenging to treat. Advances in genetic testing now allow for early identification of at-risk individuals by analyzing blood DNA, long before symptoms emerge. However, options for preventing the disease in its early stages have been limited.

In this groundbreaking study, Professor George Vassiliou and his team focused on abnormal blood stem cells carrying a common mutation in the DNMT3A gene, responsible for initiating 10–15% of AML cases. By examining blood stem cells from genetically modified mice with similar mutations, the researchers discovered that these cells rely heavily on mitochondrial metabolism for energy. This dependence presents a potential vulnerability.

Using a genome-wide screening approach, the team demonstrated that drugs targeting mitochondrial function, such as metformin, significantly slowed the growth of mutation-carrying blood cells in mice. Further experiments indicated that metformin could have a similar inhibitory effect on human blood cells with the DNMT3A mutation.

Malgorzata Gozdecka, the study’s first author, explained, "Metformin impacts mitochondrial metabolism, which these pre-cancerous cells depend on. By disrupting this energy supply, we can prevent these cells from expanding and advancing toward leukemia, and we may even reverse some of the effects caused by the mutation."

The researchers also analyzed data from over 412,000 volunteers within the UK Biobank, finding that those taking metformin were less likely to carry changes in the DNMT3A gene, suggesting a protective association that remained robust after accounting for other factors like diabetes status and BMI.

Professor Brian Huntly, a co-lead of the study, emphasized that metformin’s targeted action makes it a promising candidate for preventative therapy specifically aimed at genetic mutations linked to AML. He noted, "Our extensive research spanning cell studies to population data strongly supports moving forward with clinical trials. Importantly, as metformin is already widely used and has a well-established safety profile, it could be repurposed quickly if proven effective."

Blood cancer advocate Dr. Rubina Ahmed highlighted the urgent need for new strategies, citing the low five-year survival rate for AML patients. She expressed optimism about drug repurposing, which could accelerate the availability of preventive treatments.

The study’s next phase involves clinical trials to test metformin’s efficacy in humans with high-risk genetic mutations. Given its current approval for diabetes treatment, repurposing metformin could significantly shorten the timeline to bring a leukemia prevention option to patients in need.