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While promising in in vitro cell-line studies, the combination failed to demonstrate any benefit on disease progression in an in vivo mouse model of MPN ( Combination with Hydroxyurea (HU): A Bolivian pilot study of 10 high-risk PV patients — including five who were HU-refractory — found that adding atorvastatin to low-dose HU and aspirin reduced hematocrit, leukocyte, and platelet counts with no thrombotic events over a median 2.6-year follow-up ( 2.3 Metformin Metformin, a first-line oral therapy for type 2 diabetes, has garnered significant attention for its pleiotropic anti-cancer effects, making it a compelling candidate for drug repurposing in MPNs ( 2.3.1 Mechanistic rationale Metformin’s primary anti-cancer properties are attributed to its ability to activate AMP-activated protein kinase (AMPK) ( α through AMPK-linked inhibition of NF- κ B ( 2.3.2 Preclinical evidence in MPNs Metformin’s effects on JAK2V617F-positive MPNs were investigated in comparison to ruxolitinib ( 2.3.3 Impact of metformin use in PV and MPNs Small scale clinical trials have explored metformin’s therapeutic potential in MPNs

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Limited data exist in human populations to describe their efficacy in doing so