Metformin Use Reduces MPN Diagnosis Risk

"We saw the strongest effect in people who had taken metformin for more than 5 years as compared with those who had taken the treatment for less than a year," according to study author Daniel Tuyet Kristensen, MD, PhD.

Metformin use was found to significantly lower the likelihood of developing myeloproliferative neoplasms (MPN), which may also be useful in preventing the development of additional cancers, according to findings from a meta-analysis published in Blood Advances.¹

The odds ratio (OR) of developing MPN for patients categorized as ever-users of metformin was 0.84 (95% CI, 0.73-0.96), and the adjusted OR (aOR) was 0.70 (95% CI, 0.61-0.81). Patients categorized as long-term metformin users of 5 years or more had an OR of 0.57 (95% CI, 0.42-0.79) and an aOR of 0.45 (95% CI, 0.33-0.63).

“We were surprised by the magnitude of the association we saw in the data. We saw the strongest effect in people who had taken metformin for more than 5 years as compared with those who had taken the treatment for less than a year,” lead study author Daniel Tuyet Kristensen, MD, PhD, student at Aalborg University Hospital, said in a press release.²

Metformin is typically used to treat type 2 diabetes mellitus. Previous research involving metformin in oncology use has found a reduction in solid tumor risk but has been inconsistent between studies and solid tumor types. Additionally, preclinical studies have shown the antileukemia effect in myeloid neoplasms.

Patients in Denmark were enrolled between 2010 and 2018. Individuals were categorized as those with MPN (cases) or the matched population from the Danish general population (controls). Investigators described ever-use metformin as having redeemed 1 prescription prior to the index date. Long-term use was defined as having 5 or more years of consecutive metformin use before MPN diagnosis.

Additionally, the cumulative treatment duration was based on the World Health Organization’s daily dose of metformin at 2000 mg plus an additional 25% of days to accommodate variations in prescription filling and non-compliance.

A total of 3816 cases were analyzed along with 19,080 matched controls. Patients in the cohort had polycythemia vera (PV; 34.2%), essential thrombocythemia (ET; 34.3%), myelofibrosis (MF; 15.0%), and unclassified MPN (MPN-U; 16.5%). Overall, 96% of cases had data on molecular testing, with the most prevalent being JAK2-V617F (78.4%) and CALR mutations (5.0%).

The primary analysis focused on 7.0% of total cases categorized as ever-use of metformin vs 8.2% of controls. For long-term use, rates were 1.1% to 2.0%, respectively.

The full adjusted model showed a dose-response relationship with an aOR of 0.79 (95% CI, 0.62-1.00) for less than 1 year, 0.78 (95% CI, 0.64-0.95) for 1 to 4.99 years, 0.42 (95% CI, 0.29-0.61) for 5 to 9.99 years, and 0.56 (95% CI, 0.30-1.03) for more than 10 years.

A stratified analysis included patients with long-term treatment. The aOR for those younger than 60 was 0.47 (95% CI, 0.15-1.50); for those between 60 to 75 years, it was 0.45 (95% CI, 0.28-0.71); and for those older than 75 years, it was 0.46 (95% CI, 0.27-0.78). Long-term use remained consistent by sex but was more pronounced in male individuals with an aOR of 0.37 (95% CI, 0.23-0.60) vs 0.56 (95% CI, 0.36-0.89).

All subtypes of MPN showed the protective effect of metformin, including PV (aOR, 0.45; 95% CI, 0.26-0.77); ET (aOR, 0.33; 95% CI, 0.16-0.67); MF (aOR, 0.65; 95% CI, 0.32-1.33); and MPN-U (aOR, 0.46; 95% CI, 0.20-1.06). Regarding molecular subtypes, there was a protective effect with JAK2-V617F (aOR, 0.47; 95% CI, 0.32-0.68) and CALR mutations (aOR, 0.53; 95% CI, 0.11-2.50).

When the analysis was restricted to cases and controls without autoimmune disease, results were similar to the primary analysis (aOR, 0.46; 95% CI, 0.32-0.64).

References

1. Kristensen DT, Øvlisen AK, Jakobsen LH, et al. Metformin use and risk of myeloproliferative neoplasms - a Danish population-based case-control study. Blood Adv. 2024. doi:10.1182/bloodadvances.2023012266
2. Anti-diabetic treatment associated with reduced risk of developing blood cancer. News release. American Society of Hematology. May 17, 2024. Accessed May 23, 2024. https://shorturl.at/Ydgp9