An Oncologist’s Perspective on Metformin Use and Acute Lymphoblastic Leukemia Outcomes
Abstract
A randomized controlled clinical trial of an intensive insulin regimen in patients with hyperglycemic acute lymphoblastic leukemia (ALL) was terminated early due to futility regarding ALL clinical outcomes, despite improved glycemic control. Of note, a surrogate measure of exogenous insulin usage (molar insulin-to-C [I/C] peptide ratio) was associated with decreased overall survival, whereas metformin and thiazolidinedione treatment was associated with improved progression-free survival. Although there were differences between the 2 cohorts, for example, older and more patients with Philadelphiapositive ALL in the intensive insulin arm, multivariate analysis demonstrated that only age 60 years, glucose levels 180 mg/dL, and high I/C levels predicted overall survival. These data suggest that improved glycemic control alone may not be sufficient to impact ALL outcomes. Although the presence of an unidentified confounding factor antagonizing the beneficial effects of improved glycemic control could have contributed to the poor outcome of insulin-treated patients, another interpretation of these data point to the specific drugs used for glycemic control in these patients as potential culprits. Accumulating experimental data suggest that insulin and metformin exert conflicting effects on ALL cell biology. Metformin and thiazolidinediones may enhance chemosensitivity through their effects on AKT/mammalian target of rapamycin (mTOR) pathways. Metformin appears to exert direct toxic…
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Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design.
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