Metformin Er 500 side effects: what 299,016 FDA adverse event reports show
Drug class
Not stated in label
Label matched
Metformin Er 500 Mg (Metformin)
Who reports
299,016 reports · 68% serious · 24,489 with death outcome · 54% female
Used for
Metformin hydrochloride extended-release tablets are indicated as an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients 10 years of age and older with type 2 diabetes mellitus. Metformin hydrochloride extended-rel.
What it is
Metformin is a member of the class of guanidines that is biguanide the carrying two methyl substituents at position 1. It has a role as a geroprotector, a hypoglycemic agent, a xenobiotic and an environmental contaminant.
Boxed warning
LACTIC ACIDOSIS Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. The onset of metformin-associated lactic acidosis is often subtle, accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, somnolence, and abdominal pain.
Causality screen of the 40 strongest signals
What the badges mean
- Labeled — boxed warning The term (or its clinical synonym) appears in the FDA boxed warning: causality is regulator-recognised and considered serious.
- Labeled adverse reaction The exact term appears in the label's warnings or adverse-reactions sections: a known, expected effect. The FAERS signal confirms the label rather than discovering anything.
- Labeled (related wording) The label describes this effect under different wording (e.g. 'neutropenia' for 'neutrophil count decreased'). Treated as known.
- Likely indication confounding The term appears in the label's indications: reports probably describe the disease being treated (or its progression), not a drug effect. Classic confounding by indication.
- Reporting / coding artifact An administrative, monitoring or exposure term (product issue, off-label use, 'test normal', overdose...). Not a biological reaction; a high PRR here reflects how reports are coded.
- Lab value / disease marker A laboratory result, investigation or disease-activity marker (antibody positive, CRP abnormal, swollen joint count) not described in the label. These usually mirror the monitored disease or testing protocol rather than a drug effect; not screened further.
- Not in label — unassessed Not found in the label text, not an artifact pattern. This is a genuine candidate for a formal causality assessment (Bradford Hill / WHO-UMC); it has NOT had one here.
Strongest disproportionality signals
Flagged terms (PRR ≥ 2, χ² ≥ 4, n ≥ 10), ranked by PRR; infinite PRRs (no comparator reports) excluded. The EBGM column is a second, shrinkage-based estimate (MGPS) with its 5th percentile EB05 and the BCPNN IC025; a pair flagged by PRR alone is marked PRR-only and should be read as fragile. The strata column recomputes the PRR on serious reports only (and, for the 300 most-reported drugs, adjusted for age band), and flags pairs whose reports are unusually skewed by sex or come mostly from consumers. Each row also shows the PRR against the other drugs of the same FDA class, which removes most confounding by the condition being treated, and a calibrated p-value: on validation, known non-causes average an ROR of about 2, so significance is judged against that empirical null (✓ = p < 0.05 after calibration). 1,107 further terms are in the interactive explorer. Reaction links open the term's cross-drug page.
| Reaction | Reports | PRR 95% CI · ROR · χ²/p | EBGM EB05 · IC025 | Label screen | Serious-only & strata | Trial cross-check |
|---|---|---|---|---|---|---|
| Lactic acidosis | 12,763 | 46.0 45.0–47.1ROR 48.0 · calibrated p 2e-5 ✓ | 27.9 EB05 27.5 · IC025 +4.8 3/3 methods agree | Labeled — boxed warning exact term | age-adj. PRR 35.0 · serious PRR 23.6 · 97% clinician | not reported in cached trials |
| Neurologic neglect syndrome | 211 | 42.1 35.4–49.9ROR 42.1 · calibrated p 4e-5 ✓ | 26.3 EB05 23.5 · IC025 +4.4 3/3 methods agree | Not in label — unassessed | serious n=211 · ♀ 100% (drug 54%) · 100% clinician | not reported in cached trials |
| Euglycaemic diabetic ketoacidosis | 1,378 | 36.8 34.4–39.2ROR 36.9 · calibrated p 8e-5 ✓ | 24.2 EB05 23.2 · IC025 +4.5 3/3 methods agree | Labeled (related wording) related wording | serious n=1,373 · 94% clinician | not reported in cached trials |
| Diabetic metabolic decompensation | 368 | 25.1 22.3–28.3ROR 25.1 · calibrated p 7e-4 ✓ | 18.6 EB05 17.1 · IC025 +4.0 3/3 methods agree | Labeled (related wording) related wording | serious n=368 · 100% clinician | not reported in cached trials |
| Carotid artery thrombosis | 213 | 23.1 19.7–26.9ROR 23.1 · calibrated p 0.001 ✓ | 17.5 EB05 15.6 · IC025 +3.8 3/3 methods agree | Not in label — unassessed | serious n=213 · ♀ 100% (drug 54%) · 100% clinician | not reported in cached trials |
| Hyperlactacidaemia | 633 | 21.9 20.0–23.9ROR 21.9 · calibrated p 0.001 ✓ | 16.8 EB05 15.7 · IC025 +3.9 3/3 methods agree | Not in label — unassessed | serious n=633 · 100% clinician | not reported in cached trials |
| Catarrh | 167 | 16.0 13.5–19.0ROR 16.0 · calibrated p 0.006 ✓ | 13.1 EB05 11.5 · IC025 +3.4 3/3 methods agree | Not in label — unassessed | serious n=166 · ♀ 0% (drug 54%) · 100% clinician | not reported in cached trials |
| Adjustment disorder | 224 | 14.4 12.4–16.6ROR 14.4 · calibrated p 0.009 ✓ | 12.0 EB05 10.7 · IC025 +3.3 3/3 methods agree | Not in label — unassessed | serious n=222 · ♀ 100% (drug 54%) · 100% clinician | not reported in cached trials |
| Gastrointestinal hypomotility | 380 | 14.2 12.7–15.9ROR 14.2 · calibrated p 0.009 ✓ | 11.9 EB05 10.9 · IC025 +3.4 3/3 methods agree | Not in label — unassessed | serious n=376 · 100% consumer | not reported in cached trials |
| Glycosylated haemoglobin abnormal | 196 | 13.7 11.8–16.0ROR 13.8 · calibrated p 0.010 ✓ | 11.5 EB05 10.2 · IC025 +3.3 3/3 methods agree | Lab value / disease marker | 100% consumer | not reported in cached trials |
| Glycosylated haemoglobin increased | 4,081 | 13.4 13.0–13.8ROR 13.6 · calibrated p 0.010 ✓ | 11.4 EB05 11.1 · IC025 +3.5 3/3 methods agree | Lab value / disease marker | serious PRR 9.7 | not reported in cached trials |
| Anion gap increased | 212 | 13.0 11.2–15.1ROR 13.0 · calibrated p 0.013 ✓ | 11.0 EB05 9.8 · IC025 +3.2 3/3 methods agree | Labeled (related wording) related wording | serious n=208 · ♀ 0% (drug 54%) · 100% clinician | not reported in cached trials |
| Ketoacidosis | 1,158 | 12.7 11.9–13.5ROR 12.7 · calibrated p 0.013 ✓ | 10.8 EB05 10.3 · IC025 +3.3 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 9.2 | not reported in cached trials |
| Metabolic acidosis | 4,822 | 12.4 12.1–12.8ROR 12.6 · calibrated p 0.014 ✓ | 10.7 EB05 10.4 · IC025 +3.4 3/3 methods agree | Labeled adverse reaction exact term | age-adj. PRR 11.1 · serious PRR 9.1 · 95% clinician | not reported in cached trials |
| Diabetic ketoacidosis | 3,568 | 12.1 11.7–12.5ROR 12.2 · calibrated p 0.016 ✓ | 10.4 EB05 10.1 · IC025 +3.3 3/3 methods agree | Labeled adverse reaction exact term | age-adj. PRR 13.1 · serious PRR 8.8 | not reported in cached trials |
| Glycosylated haemoglobin decreased | 223 | 11.3 9.8–13.0ROR 11.3 · calibrated p 0.022 ✓ | 9.7 EB05 8.7 · IC025 +3.0 3/3 methods agree | Lab value / disease marker | 100% consumer | not reported in cached trials |
| Diabetes mellitus inadequate control | 2,387 | 10.8 10.3–11.3ROR 10.9 · calibrated p 0.024 ✓ | 9.4 EB05 9.1 · IC025 +3.2 3/3 methods agree | Labeled (related wording) related wording | serious PRR 8.1 | not reported in cached trials |
| Impaired gastric emptying | 1,668 | 10.4 9.9–11.0ROR 10.5 · calibrated p 0.028 ✓ | 9.2 EB05 8.8 · IC025 +3.1 3/3 methods agree | Not in label — unassessed | serious PRR 8.3 · 89% consumer | not reported in cached trials |
| Product monitoring error | 178 | 9.8 8.4–11.5ROR 9.8 · calibrated p 0.035 ✓ | 8.6 EB05 7.6 · IC025 +2.8 3/3 methods agree | Reporting / coding artifact | serious n=178 · ♀ 0% (drug 54%) · 100% clinician | not reported in cached trials |
| Bladder transitional cell carcinoma | 174 | 9.6 8.2–11.2ROR 9.6 · calibrated p 0.039 ✓ | 8.4 EB05 7.4 · IC025 +2.8 3/3 methods agree | Not in label — unassessed | serious n=174 | not reported in cached trials |
| Suspected suicide | 578 | 9.5 8.8–10.4ROR 9.6 · calibrated p 0.038 ✓ | 8.5 EB05 7.9 · IC025 +2.9 3/3 methods agree | Not in label — unassessed | serious n=578 · 100% clinician | not reported in cached trials |
| Vitamin b12 deficiency | 482 | 9.4 8.6–10.4ROR 9.4 · calibrated p 0.039 ✓ | 8.4 EB05 7.8 · IC025 +2.9 3/3 methods agree | Labeled (related wording) related wording | serious n=459 | not reported in cached trials |
| Hypoglycaemia (low blood sugar) | 5,729 | 9.3 9.0–9.5ROR 9.4 · calibrated p 0.039 ✓ | 8.3 EB05 8.1 · IC025 +3.0 3/3 methods agree | Labeled — boxed warning exact term | age-adj. PRR 7.6 · serious PRR 7.3 | not reported in cached trials |
| Diabetic neuropathy | 575 | 9.0 8.3–9.9ROR 9.1 · calibrated p 0.045 ✓ | 8.1 EB05 7.5 · IC025 +2.9 3/3 methods agree | Likely indication confounding shares a disease stem with the indications wording | serious n=485 | not reported in cached trials |
| Blood bicarbonate decreased | 216 | 8.8 7.7–10.2ROR 8.8 · calibrated p 0.050 ✓ | 7.8 EB05 7.0 · IC025 +2.7 3/3 methods agree | Lab value / disease marker | serious n=215 · 100% clinician | not reported in cached trials |
| Blood lactic acid increased | 587 | 8.7 8.0–9.5ROR 8.7 · calibrated p 0.051 | 7.8 EB05 7.3 · IC025 +2.8 3/3 methods agree | Lab value / disease marker | serious n=579 · 100% clinician | not reported in cached trials |
| Neuritis | 172 | 8.7 7.4–10.2ROR 8.7 · calibrated p 0.052 | 7.7 EB05 6.8 · IC025 +2.7 3/3 methods agree | Not in label — unassessed | serious n=170 · ♀ 0% (drug 54%) · 100% clinician | not reported in cached trials |
| Blood pressure diastolic abnormal | 284 | 8.6 7.6–9.7ROR 8.6 · calibrated p 0.054 | 7.7 EB05 6.9 · IC025 +2.7 3/3 methods agree | Lab value / disease marker | serious n=281 · ♀ 100% (drug 54%) · 100% clinician | not reported in cached trials |
| Hyperparathyroidism secondary | 277 | 8.5 7.5–9.6ROR 8.5 · calibrated p 0.056 | 7.6 EB05 6.9 · IC025 +2.7 3/3 methods agree | Not in label — unassessed | serious n=277 | not reported in cached trials |
| Nephrogenic anaemia | 503 | 8.3 7.6–9.2ROR 8.4 · calibrated p 0.059 | 7.5 EB05 7.0 · IC025 +2.8 3/3 methods agree | Not in label — unassessed | serious n=503 | not reported in cached trials |
| Hypoglycaemic coma | 308 | 8.2 7.3–9.3ROR 8.3 · calibrated p 0.061 | 7.4 EB05 6.7 · IC025 +2.7 3/3 methods agree | Not in label — unassessed | serious n=308 · 100% clinician | not reported in cached trials |
| Blood glucose abnormal | 1,843 | 7.6 7.3–8.0ROR 7.7 · calibrated p 0.075 | 7.0 EB05 6.7 · IC025 +2.7 3/3 methods agree | Lab value / disease marker | serious PRR 6.6 · 71% consumer | NCT02722239: 13/40 (32.5%) on Metformin Er 500 |
| Insulin resistance | 203 | 7.6 6.6–8.8ROR 7.6 · calibrated p 0.079 | 6.8 EB05 6.1 · IC025 +2.5 3/3 methods agree | Reporting / coding artifact | – | not reported in cached trials |
| Blood glucose fluctuation | 1,078 | 7.5 7.1–8.0ROR 7.5 · calibrated p 0.080 | 6.9 EB05 6.5 · IC025 +2.7 3/3 methods agree | Lab value / disease marker | serious n=573 · 72% consumer | not reported in cached trials |
| Distributive shock | 214 | 7.4 6.4–8.5ROR 7.4 · calibrated p 0.085 | 6.7 EB05 6.0 · IC025 +2.5 3/3 methods agree | Not in label — unassessed | serious n=214 · ♀ 0% (drug 54%) · 100% clinician | not reported in cached trials |
| Diabetic retinopathy | 327 | 7.4 6.6–8.3ROR 7.4 · calibrated p 0.086 | 6.7 EB05 6.1 · IC025 +2.6 3/3 methods agree | Likely indication confounding shares a disease stem with the indications wording | serious n=297 | not reported in cached trials |
| Personality disorder | 253 | 7.3 6.5–8.4ROR 7.3 · calibrated p 0.087 | 6.7 EB05 6.0 · IC025 +2.5 3/3 methods agree | Not in label — unassessed | serious n=249 · ♀ 100% (drug 54%) · 100% clinician | not reported in cached trials |
| Acute kidney injury (sudden kidney damage) | 14,181 | 7.1 7.0–7.2ROR 7.4 · calibrated p 0.084 | 6.5 EB05 6.4 · IC025 +2.7 3/3 methods agree | Labeled — boxed warning synonym match | age-adj. PRR 5.6 · serious PRR 5.5 | not reported in cached trials |
| Blood pressure systolic abnormal | 228 | 7.0 6.1–8.0ROR 7.0 · calibrated p 0.101 | 6.3 EB05 5.7 · IC025 +2.4 3/3 methods agree | Lab value / disease marker | serious n=222 · ♀ 100% (drug 54%) · 100% clinician | not reported in cached trials |
| Injection site nodule | 1,001 | 6.9 6.5–7.4ROR 7.0 · calibrated p 0.101 | 6.4 EB05 6.0 · IC025 +2.6 3/3 methods agree | Not in label — unassessed | 79% consumer | not reported in cached trials |
Clinical concept groups
MedDRA splits one clinical problem across several terms (e.g. "neutropenia", "neutrophil count decreased", "agranulocytosis"), which dilutes term-level signals. These rows count reports with any term in a concept group (an exact union, not a sum), compared with all other drugs. Groups are hand-built and listed in the methods.
| Concept | Reports | PRR 95% CI | Reading |
|---|---|---|---|
| Hypoglycaemia | 9,722 | 7.87.7–8.0 | signal |
| Hyperglycaemia / diabetes | 28,515 | 6.26.1–6.3 | signal |
| Kidney injury | 23,364 | 3.73.7–3.8 | signal |
| Pancreatitis | 3,962 | 3.63.5–3.7 | signal |
| Hyponatraemia | 2,439 | 2.22.1–2.2 | signal |
| Rhabdomyolysis / myopathy | 2,365 | 2.12.0–2.2 | raised |
| Gi bleeding | 4,656 | 1.81.8–1.9 | raised |
| Arrhythmia / qt | 4,874 | 1.81.7–1.8 | raised |
| Heart failure | 4,016 | 1.61.5–1.6 | raised |
| Myocardial infarction | 4,548 | 1.61.5–1.6 | raised |
| Fall / fracture | 8,445 | 1.61.5–1.6 | raised |
| Anaemia | 6,247 | 1.51.4–1.5 | raised |
| Serious infection | 15,676 | 1.41.4–1.5 | raised |
| Suicidality | 4,984 | 1.41.4–1.5 | raised |
| Stroke | 4,864 | 1.41.3–1.4 | raised |
| Liver injury | 5,406 | 1.31.2–1.3 | raised |
Trial evidence (ClinicalTrials.gov)
✓ Trial adverse-event data found on ClinicalTrials.gov
Largest completed trials with posted results that list Metformin Er 500 as a study intervention. The right-hand column of the signal table shows whether each FAERS term was also recorded in these trials, with a real denominator (1 of 40 signal terms matched).
- NCT03861767 — REMAP Trial for Optimizing Surgical Outcomes at UPMC (N=302, PHASE3; 30 AE terms posted; arms: SPRY: Metformin LD-SC (Low-dose, Short C; SPRY: Metformin LD-IC (Low-dose, Interme; SPRY: Metformin LD-LC (Low-dose, Long Co; SPRY: Metformin ID-SC (Intermediate-dose)
- NCT02722239 — An Open-label, Randomized, Crossover Study of Comparative Pharmacokinetics and Bioequivalence of Dapagliflozin (N=40, PHASE1; 4 AE terms posted; arms: Test Product (T); Reference Product (R))
Caveats: trial populations, doses and follow-up differ from the reporting population; AE terms are sponsor-coded and matched here by wording; absence from a trial list means the term was not reported above the sponsor's frequency threshold, not that it cannot occur.
Most frequently reported reactions
By raw co-report count, regardless of disproportionality. Common terms here are often the illness itself or generic outcomes.
| Reaction | Reports | PRR 95% CI · ROR · χ²/p | EBGM EB05 · IC025 | Label screen | Serious-only & strata | Trial cross-check |
|---|---|---|---|---|---|---|
| Nausea | 19,666 | 1.8 1.7–1.8ROR 1.8 · calibrated p 0.842 | 1.7 EB05 1.7 · IC025 +0.8 | Labeled adverse reaction exact term | age-adj. PRR 1.6 · serious PRR 1.7 | not reported in cached trials |
| Diarrhoea (diarrhea) | 18,902 | 2.1 2.1–2.1ROR 2.2 · calibrated p 0.968 | 2.1 EB05 2.0 · IC025 +1.0 3/3 methods agree | Labeled adverse reaction exact term | age-adj. PRR 1.8 · serious PRR 2.0 | not reported in cached trials |
| Blood glucose increased | 17,005 | 6.8 6.7–6.9ROR 7.2 · calibrated p 0.091 | 6.3 EB05 6.2 · IC025 +2.6 3/3 methods agree | Lab value / disease marker | age-adj. PRR 5.1 · serious PRR 5.4 · 79% consumer | NCT02722239: 13/40 (32.5%) on Metformin Er 500 |
| Drug ineffective (drug did not work) | 16,333 | 0.9 0.9–0.9ROR 0.9 · calibrated p 0.219 | 0.9 EB05 0.9 · IC025 -0.2 PRR-only: not supported by EBGM or IC | Reporting / coding artifact | age-adj. PRR 1.0 · serious PRR 1.0 | not reported in cached trials |
| Fatigue (tiredness) | 15,039 | 1.4 1.3–1.4ROR 1.4 · calibrated p 0.564 | 1.4 EB05 1.3 · IC025 +0.4 | Labeled (related wording) related wording | age-adj. PRR 1.2 · serious PRR 1.4 | not reported in cached trials |
| Acute kidney injury (sudden kidney damage) | 14,181 | 7.1 7.0–7.2ROR 7.4 · calibrated p 0.084 | 6.5 EB05 6.4 · IC025 +2.7 3/3 methods agree | Labeled — boxed warning synonym match | age-adj. PRR 5.6 · serious PRR 5.5 | not reported in cached trials |
| Vomiting | 13,070 | 2.0 1.9–2.0ROR 2.0 · calibrated p 0.959 | 2.0 EB05 1.9 · IC025 +0.9 | Labeled adverse reaction exact term | age-adj. PRR 2.0 · serious PRR 1.9 | not reported in cached trials |
| Lactic acidosis | 12,763 | 46.0 45.0–47.1ROR 48.0 · calibrated p 2e-5 ✓ | 27.9 EB05 27.5 · IC025 +4.8 3/3 methods agree | Labeled — boxed warning exact term | age-adj. PRR 35.0 · serious PRR 23.6 · 97% clinician | not reported in cached trials |
| Off label use (used outside approved label) | 12,093 | 1.0 1.0–1.0ROR 1.0 · calibrated p 0.291 | 1.0 EB05 1.0 · IC025 -0.1 PRR-only: not supported by EBGM or IC | Reporting / coding artifact | age-adj. PRR 1.0 · serious PRR 1.1 | not reported in cached trials |
| Dyspnoea (shortness of breath) | 11,614 | 1.4 1.4–1.5ROR 1.5 · calibrated p 0.620 | 1.4 EB05 1.4 · IC025 +0.5 | Not in label — unassessed | age-adj. PRR 1.3 · serious PRR 1.4 | not reported in cached trials |
| Weight decreased (weight loss) | 10,909 | 2.8 2.8–2.9ROR 2.9 · calibrated p 0.666 | 2.7 EB05 2.7 · IC025 +1.4 3/3 methods agree | Not in label — unassessed | age-adj. PRR 2.3 · serious PRR 2.2 | not reported in cached trials |
| Dizziness | 10,647 | 1.5 1.5–1.5ROR 1.5 · calibrated p 0.661 | 1.5 EB05 1.5 · IC025 +0.6 | Labeled adverse reaction exact term | age-adj. PRR 1.3 · serious PRR 1.5 | not reported in cached trials |
| Headache | 10,333 | 1.2 1.1–1.2ROR 1.2 · calibrated p 0.417 | 1.2 EB05 1.1 · IC025 +0.2 | Labeled adverse reaction exact term | age-adj. PRR 1.1 · serious PRR 1.3 | not reported in cached trials |
| Pain | 10,185 | 1.2 1.1–1.2ROR 1.2 · calibrated p 0.419 | 1.2 EB05 1.1 · IC025 +0.2 | Labeled — boxed warning exact term | age-adj. PRR 1.3 · serious PRR 1.1 | not reported in cached trials |
| Malaise (feeling unwell) | 9,058 | 1.5 1.4–1.5ROR 1.5 · calibrated p 0.621 | 1.4 EB05 1.4 · IC025 +0.5 | Labeled — boxed warning exact term | age-adj. PRR 1.4 · serious PRR 1.5 | not reported in cached trials |
Unlabeled candidate signals
These flagged terms were not found in the FDA label text and do not match an artifact pattern. They are the pairs that would merit a structured assessment (temporality, dose-response, biological plausibility, consistency across databases, trial or cohort evidence). The screen has not done that; string-matching misses label wording, and a strong PRR can still be stimulated reporting, co-medication, or the disease itself.
- Neurologic neglect syndrome — n=211, PRR 42.1
- Carotid artery thrombosis — n=213, PRR 23.1
- Hyperlactacidaemia — n=633, PRR 21.9
- Catarrh — n=167, PRR 16.0
- Adjustment disorder — n=224, PRR 14.4
- Gastrointestinal hypomotility — n=380, PRR 14.2
- Impaired gastric emptying — n=1,668, PRR 10.4
- Bladder transitional cell carcinoma — n=174, PRR 9.6
- Suspected suicide — n=578, PRR 9.5
- Neuritis — n=172, PRR 8.7
✓ A hand-written Bradford Hill causality assessment exists for this drug: Metformin ↔ Lactic acidosis.
Want to assess one of these properly? The runbook describes the Bradford Hill / trial-evidence workflow used on the assessment page, and handoff_top1000_signals.csv lists the strongest unassessed pairs across all drugs.
Common questions
What are the most reported side effects of Metformin Er 500?
In FDA FAERS, the most frequently co-reported reaction terms for Metformin Er 500 are nausea, diarrhoea, blood glucose increased, fatigue, acute kidney injury, vomiting. These are report counts, not rates: FAERS has no denominator, reporting is voluntary and uneven, and a term can be reported because of the illness being treated rather than the drug.
Does Metformin Er 500 have an FDA boxed warning?
Yes. The current FDA label carries a boxed warning: LACTIC ACIDOSIS Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. The onset of metformin-associated lactic acidosis is often subtle, accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, somnolence, and abdominal pain.
Do FAERS signals prove that Metformin Er 500 causes these side effects?
No. A disproportionality signal (PRR, ROR) means a reaction is reported more often with this drug than with others in the database. That can reflect a real effect, but also the disease being treated, stimulated reporting after news or litigation, co-medications, or how reports are coded. Causality needs temporality, dose-response, biological plausibility, consistency across data sources and, ideally, trial or cohort evidence. This page screens each term against the FDA label and ClinicalTrials.gov results; it does not establish causation.
Sources & methods
- FDA label via openFDA (set ID 05999192-ebc6-4198-bd1e-f46abbfb4f8a, effective 20260909; matched on
openfda.generic_name.exact:"METFORMIN ER 500 MG") - PubChem CID 4091 description (ChEBI)
- Bayesian shrinkage measures computed offline over all 1,317,300 cached pairs: BCPNN information component (IC, with Norén closed-form IC025) and MGPS empirical-Bayes geometric mean (EBGM, EB05) with a two-component gamma prior fitted by maximum marginal likelihood (α₁=0.57, β₁=0.02, α₂=1.42, β₂=0.70, w=0.17); unstratified
- FAERS pair statistics from the OpenPV build of 2026-09-14 (openFDA
count=aggregation, fieldpatient.drug.openfda.generic_name.exact, 1,147 reaction terms, min 3 co-reports); PRR/ROR with 95% CI, chi-square with Yates correction - Serious-only and stratified counts (serious:1, patient.patientsex, primarysource.qualification) from openFDA count queries; serious-only PRR uses the drug serious report total and the term global serious total (N_serious=11,882,979); strata shown only when n ≥ 20
- Seriousness and sex counts from openFDA
count=serious,patient.patientsex,seriousnessdeath - ClinicalTrials.gov API v2 (query
METFORMIN ER 500, results-bearing studies sorted by enrollment)
Page generated 2026-10-14. Label and PubChem text are retrieved automatically and may lag the current label; always check the current prescribing information. OpenPV is a beta research tool of the Open Source Medicine Foundation.