← All causality assessments
Causality: well established
Causality assessment · Causality: well established
Metformin Hydrochloride and Lactic Acidosis: is the FAERS signal real?
A written Bradford Hill assessment of one drug–event pair. The grade is a judgement about the signal, not a statement that this drug causes this event in any one person; FAERS counts are reports, not rates.
Metformin Hydrochloride ↔ Lactic Acidosis
n=4,538 co-reports · PRR 58.7 · ROR 63.5
Metformin is the most-prescribed oral antidiabetic. Lactic acidosis is a longstanding regulatory concern; the boxed warning (updated 2016) describes the risk in contraindicated patients. 4,538 co-reports (PRR 58.7), but most cases involve renal/hepatic contraindications. Large controlled studies showed no excess without contraindications.
Boxed warning: metformin label. FDA Dsc 2016. BMJ 2015, PMID: 25610917. Diabetes Care 2017, PMID: 28377746.
| Bradford Hill viewpoint | Status | Note |
|---|---|---|
| Temporality (necessary) | met | Documented in label |
| Strength | met | PRR 58.7 |
| Consistency | not established | Not reproduced when contraindications excluded |
| Specificity | partial | Specific to biguanide class |
| Biological gradient | met | Risk increases with renal decline |
| Plausibility | met | Mitochondrial mechanism known |
| Coherence | met | Coherent with PK |
| Experiment | n/a | Not an RCT endpoint |
| Analogy | met | Phenformin same effect |
This table is this page's own qualitative read of the literature cited above, not an automated or citation-gated assessment — see the note at the bottom of this page.
✗ No ClinicalTrials.gov results-posting trial in the top search hits for Metformin captured lactic acidosis as a tracked adverse event in a usable structure. Lactic acidosis is rare; metformin RCTs are not powered to detect it.