Metformin
The first-line drug for type 2 diabetes, used by over 100 million people worldwide, and one whose exact mechanism is still not fully settled. Two variants here move how well it works, not whether someone should take it.
What this drug connects to
The genes involved
The gene behind this variant is better known for something else entirely — ATM is the ataxia telangiectasia gene, central to DNA repair and cell cycle control. Here, a common variant near it (rs11212617) predicts who responds better to metformin: found in 1,024 Scottish patients, replicated in nearly 3,000 more across two cohorts, with an odds ratio of 1.35 for treatment success. This is not a guess at a mechanism — in a follow-up cell experiment, blocking ATM blunted metformin's activation of AMPK, the enzyme metformin is known to work through, placing ATM upstream in that pathway. Metformin stays first-line regardless of genotype; this is about how well it is likely to work, not whether to prescribe it.
Zhou K et al. (GoDARTS/UKPDS/MAGIC investigators), Nature Genetics 2011 — common variants near ATM and glycemic response to metformin, with cell-line mechanistic follow-up. PMID:21186350
SLC2A2 encodes GLUT2, the glucose transporter metformin's target tissue depends on. A common intronic variant (rs8192675) predicted a modestly greater HbA1c reduction from metformin across 10,577 people of European ancestry, and separately turned out to be the strongest known predictor of how much SLC2A2 gets expressed in the liver — a real mechanistic link, not just a statistical one. In obese patients specifically, the effect grew to roughly half of what adding a second drug (a DPP-4 inhibitor) would achieve. The study's own framing is "a potential biomarker for stratified medicine" — a real, mechanistically grounded lead, not yet something a guideline tells a clinician to act on.
Zhou K et al. (MetGen Consortium), Nature Genetics 2016 — SLC2A2 variation and glycemic response to metformin, with liver eQTL evidence. PMID:27500523
In the news
2026-09-16 · American Federation for Aging Research (AFAR), official TAME Trial page
The TAME trial, aiming to test whether metformin delays aging itself, has still not launched
Metformin is the center of a real scientific debate about whether a diabetes drug can delay aging itself, not just treat diabetes -- but the trial designed to actually test that, TAME (3,000 non-diabetic people aged 65-79, 14 institutions, 6 years), has not enrolled a single participant as of this check: AFAR's own page confirms it is still in fundraising, with "no results" because "enrollment has not occurred." The two variants on this page (ATM, SLC2A2) come from real diabetes pharmacogenomic studies, unrelated to the aging question TAME would test.
Whose work this rests on
Every guideline above was written by people. Named here because they are contributors to this page in the same sense anybody else on this site is.
Questions about Metformin
What is metformin?
Metformin is the first-line drug for type 2 diabetes, used by over 100 million people worldwide. Its exact mechanism is still not fully settled, and two variants on this page affect how well it works, not whether someone should take it.
Does the ATM variant (rs11212617) affect how well metformin works?
Yes. The rs11212617 variant near ATM predicted treatment success with an odds ratio of 1.35 in 1,024 Scottish patients, replicated in nearly 3,000 more. A follow-up cell experiment found blocking ATM blunted metformin’s activation of AMPK, the enzyme metformin works through — a real mechanistic link, not just a statistical one.
Does the SLC2A2 variant affect metformin’s blood sugar-lowering effect?
Yes. The rs8192675 variant near SLC2A2 (which encodes the glucose transporter GLUT2) predicted a modestly greater HbA1c reduction from metformin across 10,577 people of European ancestry, and separately predicts how much SLC2A2 is expressed in the liver. In obese patients, the effect reached roughly half of what adding a second drug would achieve.
Does the ATM or SLC2A2 variant mean I shouldn’t take metformin?
No. Metformin stays the first-line diabetes drug regardless of ATM or SLC2A2 genotype — both variants relate to how well it’s likely to work, not whether it should be prescribed.
Quoting this page
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Metformin. MyGeneLog™. https://www.mygenelog.com/drugs/metformin