Epigenetic markers associated with metformin response and intolerance in drug-naïve patients with type 2 diabetes
Abstract
Blood-based epigenetic markers differentiate metformin responsiveness and tolerance in patients recently diagnosed with type 2 diabetes. How to mete out metformin Metformin is the most commonly used drug to treat type 2 diabetes (T2D), though not all patients respond to it, and still, others do not tolerate it. García-Calzón et al. analyzed genome-wide DNA methylation in the blood of drug-naïve patients who were recently diagnosed with T2D. They found that DNA methylation at specific loci associated with future metformin response or tolerance, respectively, across multiple cohorts. These epigenetic markers may have theranostic potential regarding which patients should receive metformin. Metformin is the first-line pharmacotherapy for managing type 2 diabetes (T2D). However, many patients with T2D do not respond to or tolerate metformin well. Currently, there are no phenotypes that successfully predict glycemic response to, or tolerance of, metformin. We explored whether blood-based epigenetic markers could discriminate metformin response and tolerance by analyzing genome-wide DNA methylation in drug-naïve patients with T2D at the time of their diagnosis. DNA methylation of 11 and 4 sites differed between glycemic responders/nonresponders and metformin-tolerant/intolerant patients, respectively, in discovery and replication cohorts. Greater methylation at these sites associated with a higher risk of not responding to or not tolerating metformin with odds ratios between 1.43…
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