Metformin Extended-Release side effects: what 56,974 FDA adverse event reports show
Drug class
Not stated in label
Label matched
Metformin Hydrochloride Extended-Release Tablets (Metformin Hydrochloride)
Who reports
56,974 reports · 73% serious · 5,597 with death outcome · 55% female
Used for
Metformin hydrochloride extended-release tablets are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Metformin hydrochloride extended-release tablets are biguanide indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. (1)
What it is
Metformin hydrochloride extended-release tablets contain the biguanidine antihyperglycemic agent, metformin, in the form of monohydrochloride salt.
Boxed warning
LACTIC ACIDOSIS Post-marketing 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.
- 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). 1,164 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 |
|---|---|---|---|---|---|---|
| Heart sounds | 40 | 258.5 172.3–387.9ROR 258.7 · calibrated p 2e-10 ✓ | 141.2 EB05 108.1 · IC025 +5.2 3/3 methods agree | Not in label — unassessed | serious n=40 · ♀ 100% (drug 55%) · 100% clinician | not reported in cached trials |
| Pulmonary vasculitis | 114 | 101.1 82.2–124.5ROR 101.3 · calibrated p 1e-7 ✓ | 78.3 EB05 66.9 · IC025 +5.6 3/3 methods agree | Not in label — unassessed | serious n=114 · ♀ 0% (drug 55%) | not reported in cached trials |
| Neurologic neglect syndrome | 113 | 93.0 75.6–114.3ROR 93.1 · calibrated p 3e-7 ✓ | 73.3 EB05 62.6 · IC025 +5.5 3/3 methods agree | Not in label — unassessed | serious n=113 · ♀ 100% (drug 55%) | not reported in cached trials |
| Prolonged expiration | 40 | 65.5 46.8–91.7ROR 65.6 · calibrated p 4e-6 ✓ | 54.3 EB05 41.6 · IC025 +4.5 3/3 methods agree | Not in label — unassessed | serious n=40 · ♀ 100% (drug 55%) · 100% clinician | not reported in cached trials |
| Total lung capacity abnormal | 55 | 62.0 46.6–82.5ROR 62.1 · calibrated p 5e-6 ✓ | 52.2 EB05 41.6 · IC025 +4.7 3/3 methods agree | Not in label — unassessed | serious n=55 · ♀ 0% (drug 55%) · 100% clinician | not reported in cached trials |
| Hypocholesterolaemia | 44 | 61.3 44.5–84.3ROR 61.3 · calibrated p 6e-6 ✓ | 51.4 EB05 39.9 · IC025 +4.6 3/3 methods agree | Not in label — unassessed | serious n=44 · ♀ 100% (drug 55%) · 100% clinician | not reported in cached trials |
| Human rhinovirus test positive | 53 | 60.9 45.5–81.5ROR 61.0 · calibrated p 6e-6 ✓ | 51.4 EB05 40.8 · IC025 +4.7 3/3 methods agree | Lab value / disease marker | serious n=53 · ♀ 100% (drug 55%) · 100% clinician | not reported in cached trials |
| Capillaritis | 38 | 60.6 43.0–85.4ROR 60.6 · calibrated p 7e-6 ✓ | 50.8 EB05 38.6 · IC025 +4.4 3/3 methods agree | Not in label — unassessed | serious n=38 · ♀ 0% (drug 55%) · 100% clinician | not reported in cached trials |
| Carotid artery thrombosis | 118 | 58.9 48.5–71.6ROR 59.0 · calibrated p 6e-6 ✓ | 50.4 EB05 43.2 · IC025 +5.1 3/3 methods agree | Not in label — unassessed | serious n=118 · ♀ 100% (drug 55%) | not reported in cached trials |
| Lactic acidosis | 4,401 | 58.4 56.6–60.2ROR 63.2 · calibrated p 3e-6 ✓ | 50.4 EB05 49.2 · IC025 +5.6 3/3 methods agree | Labeled — boxed warning exact term | age-adj. PRR 45.9 · serious PRR 39.7 · 93% clinician | not reported in cached trials |
| Alveolar osteitis | 54 | 53.3 40.0–70.9ROR 53.3 · calibrated p 1e-5 ✓ | 45.9 EB05 36.5 · IC025 +4.6 3/3 methods agree | Not in label — unassessed | serious n=53 · ♀ 100% (drug 55%) · 100% clinician | not reported in cached trials |
| Urinary tract discomfort | 56 | 51.8 39.2–68.6ROR 51.9 · calibrated p 2e-5 ✓ | 44.8 EB05 35.8 · IC025 +4.6 3/3 methods agree | Not in label — unassessed | serious n=56 · ♀ 100% (drug 55%) | not reported in cached trials |
| Spirometry abnormal | 65 | 45.7 35.3–59.1ROR 45.7 · calibrated p 3e-5 ✓ | 40.2 EB05 32.7 · IC025 +4.6 3/3 methods agree | Lab value / disease marker | serious n=65 · ♀ 0% (drug 55%) | not reported in cached trials |
| Cerebral hypoperfusion | 49 | 43.9 32.6–59.0ROR 43.9 · calibrated p 4e-5 ✓ | 38.7 EB05 30.4 · IC025 +4.3 3/3 methods agree | Not in label — unassessed | serious n=49 · ♀ 0% (drug 55%) · 100% clinician | not reported in cached trials |
| Viral test positive | 37 | 41.2 29.3–57.9ROR 41.2 · calibrated p 7e-5 ✓ | 36.5 EB05 27.6 · IC025 +4.1 3/3 methods agree | Lab value / disease marker | serious n=38 · ♀ 100% (drug 55%) · 100% clinician | not reported in cached trials |
| Euglycaemic diabetic ketoacidosis | 383 | 39.0 35.1–43.4ROR 39.3 · calibrated p 6e-5 ✓ | 35.3 EB05 32.4 · IC025 +4.9 3/3 methods agree | Labeled (related wording) related wording | serious n=383 · 100% clinician | not reported in cached trials |
| Adjustment disorder | 115 | 35.5 29.3–43.0ROR 35.6 · calibrated p 1e-4 ✓ | 32.3 EB05 27.6 · IC025 +4.5 3/3 methods agree | Not in label — unassessed | serious n=115 · ♀ 100% (drug 55%) | not reported in cached trials |
| Pneumonia haemophilus | 42 | 34.6 25.2–47.5ROR 34.7 · calibrated p 2e-4 ✓ | 31.3 EB05 24.1 · IC025 +4.0 3/3 methods agree | Not in label — unassessed | serious n=42 · ♀ 100% (drug 55%) · 100% clinician | not reported in cached trials |
| Mite allergy | 55 | 34.6 26.3–45.6ROR 34.7 · calibrated p 2e-4 ✓ | 31.4 EB05 25.0 · IC025 +4.2 3/3 methods agree | Not in label — unassessed | serious n=55 · ♀ 0% (drug 55%) · 100% clinician | not reported in cached trials |
| Respiratory syncytial virus test positive | 54 | 30.4 23.1–40.2ROR 30.5 · calibrated p 3e-4 ✓ | 27.9 EB05 22.2 · IC025 +4.0 3/3 methods agree | Lab value / disease marker | serious n=54 · ♀ 100% (drug 55%) · 100% clinician | not reported in cached trials |
| Diabetic metabolic decompensation | 101 | 28.9 23.6–35.4ROR 28.9 · calibrated p 4e-4 ✓ | 26.7 EB05 22.6 · IC025 +4.2 3/3 methods agree | Labeled (related wording) related wording | serious n=101 | not reported in cached trials |
| Hypoglycaemic coma | 201 | 27.4 23.8–31.6ROR 27.5 · calibrated p 4e-4 ✓ | 25.5 EB05 22.7 · IC025 +4.4 3/3 methods agree | Not in label — unassessed | serious n=201 | not reported in cached trials |
| Mycotic allergy | 56 | 26.1 19.9–34.3ROR 26.1 · calibrated p 7e-4 ✓ | 24.3 EB05 19.4 · IC025 +3.9 3/3 methods agree | Not in label — unassessed | serious n=56 · ♀ 0% (drug 55%) · 100% clinician | not reported in cached trials |
| Neuritis | 101 | 25.8 21.1–31.5ROR 25.8 · calibrated p 6e-4 ✓ | 24.0 EB05 20.4 · IC025 +4.1 3/3 methods agree | Not in label — unassessed | serious n=101 · ♀ 0% (drug 55%) | not reported in cached trials |
| Hyperlactacidaemia | 171 | 25.4 21.8–29.7ROR 25.5 · calibrated p 7e-4 ✓ | 23.8 EB05 20.9 · IC025 +4.2 3/3 methods agree | Not in label — unassessed | serious n=171 | not reported in cached trials |
| Antineutrophil cytoplasmic antibody positive | 46 | 24.7 18.4–33.3ROR 24.8 · calibrated p 9e-4 ✓ | 23.0 EB05 18.0 · IC025 +3.7 3/3 methods agree | Lab value / disease marker | serious n=46 · ♀ 0% (drug 55%) · 100% clinician | not reported in cached trials |
| Facet joint syndrome | 199 | 24.7 21.4–28.5ROR 24.8 · calibrated p 7e-4 ✓ | 23.2 EB05 20.6 · IC025 +4.2 3/3 methods agree | Not in label — unassessed | serious n=199 · ♀ 100% (drug 55%) · 100% clinician | not reported in cached trials |
| Continuous haemodiafiltration | 61 | 24.1 18.6–31.2ROR 24.1 · calibrated p 1e-3 ✓ | 22.5 EB05 18.1 · IC025 +3.8 3/3 methods agree | Not in label — unassessed | serious n=59 · 100% clinician | not reported in cached trials |
| Animal scratch | 57 | 22.9 17.5–30.0ROR 22.9 · calibrated p 0.001 ✓ | 21.5 EB05 17.2 · IC025 +3.8 3/3 methods agree | Not in label — unassessed | serious n=57 · ♀ 100% (drug 55%) | not reported in cached trials |
| Dust allergy | 55 | 22.2 16.9–29.1ROR 22.2 · calibrated p 0.001 ✓ | 20.8 EB05 16.6 · IC025 +3.7 3/3 methods agree | Not in label — unassessed | serious n=55 · ♀ 0% (drug 55%) · 100% clinician | not reported in cached trials |
| Bronchopulmonary aspergillosis allergic | 52 | 22.1 16.7–29.2ROR 22.1 · calibrated p 0.002 ✓ | 20.7 EB05 16.4 · IC025 +3.7 3/3 methods agree | Not in label — unassessed | serious n=52 · ♀ 100% (drug 55%) · 100% clinician | not reported in cached trials |
| Ketosis | 50 | 18.7 14.1–24.8ROR 18.7 · calibrated p 0.003 ✓ | 17.7 EB05 13.9 · IC025 +3.5 3/3 methods agree | Not in label — unassessed | serious n=46 · 100% clinician | not reported in cached trials |
| Personality disorder | 127 | 18.6 15.5–22.2ROR 18.6 · calibrated p 0.003 ✓ | 17.7 EB05 15.2 · IC025 +3.8 3/3 methods agree | Not in label — unassessed | serious n=127 · ♀ 100% (drug 55%) | not reported in cached trials |
| Peripheral venous disease | 189 | 18.2 15.8–21.1ROR 18.3 · calibrated p 0.003 ✓ | 17.4 EB05 15.4 · IC025 +3.8 3/3 methods agree | Not in label — unassessed | serious n=187 · ♀ 100% (drug 55%) · 100% clinician | not reported in cached trials |
| Conjunctivitis allergic | 69 | 18.2 14.3–23.1ROR 18.2 · calibrated p 0.003 ✓ | 17.3 EB05 14.1 · IC025 +3.6 3/3 methods agree | Not in label — unassessed | serious n=69 · ♀ 0% (drug 55%) | not reported in cached trials |
| Metabolic acidosis | 1,401 | 17.0 16.1–17.9ROR 17.4 · calibrated p 0.004 ✓ | 16.3 EB05 15.6 · IC025 +3.9 3/3 methods agree | Labeled adverse reaction exact term | age-adj. PRR 15.7 · serious PRR 12.9 · 91% clinician | not reported in cached trials |
| Onychomadesis | 179 | 16.5 14.2–19.2ROR 16.6 · calibrated p 0.005 ✓ | 15.8 EB05 14.0 · IC025 +3.7 3/3 methods agree | Not in label — unassessed | serious n=177 · ♀ 100% (drug 55%) · 100% clinician | not reported in cached trials |
| Onychomycosis | 186 | 16.3 14.1–18.8ROR 16.3 · calibrated p 0.005 ✓ | 15.6 EB05 13.8 · IC025 +3.7 3/3 methods agree | Not in label — unassessed | serious n=184 · ♀ 100% (drug 55%) · 100% clinician | not reported in cached trials |
| Eosinophilic granulomatosis with polyangiitis | 85 | 16.1 13.0–20.0ROR 16.1 · calibrated p 0.006 ✓ | 15.4 EB05 12.8 · IC025 +3.5 3/3 methods agree | Not in label — unassessed | serious n=85 · ♀ 0% (drug 55%) | not reported in cached trials |
| Distributive shock | 91 | 15.8 12.8–19.4ROR 15.8 · calibrated p 0.006 ✓ | 15.1 EB05 12.6 · IC025 +3.5 3/3 methods agree | Not in label — unassessed | serious n=91 · 100% clinician | 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 | 1,945 | 7.67.3–7.9 | signal |
| Kidney injury | 5,399 | 4.44.3–4.5 | signal |
| Hyperglycaemia / diabetes | 3,973 | 4.34.1–4.4 | signal |
| Pancreatitis | 640 | 2.92.7–3.2 | signal |
| Rhabdomyolysis / myopathy | 526 | 2.42.2–2.6 | signal |
| Hyponatraemia | 491 | 2.22.1–2.5 | signal |
| Suicidality | 1,375 | 2.12.0–2.2 | raised |
| Fall / fracture | 1,943 | 1.91.8–2.0 | raised |
| Interstitial lung disease | 488 | 1.91.7–2.0 | raised |
| Heart failure | 873 | 1.81.7–1.9 | raised |
| Liver injury | 1,443 | 1.81.7–1.9 | raised |
| Anaemia | 1,339 | 1.61.6–1.7 | raised |
| Arrhythmia / qt | 825 | 1.61.5–1.7 | raised |
| Depression | 1,185 | 1.61.5–1.6 | raised |
| Serious infection | 3,173 | 1.51.5–1.6 | raised |
| Stroke | 1,021 | 1.51.4–1.6 | raised |
Trial evidence (ClinicalTrials.gov)
✓ Trial adverse-event data found on ClinicalTrials.gov
Largest completed trials with posted results that list Metformin Extended-Release 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 (0 of 40 signal terms matched).
- NCT01864174 — Phase 4: Investigational Study to Evaluate Metformin XR Monotherapy Versus Metformin IR Monotherapy in Subject (N=1736, PHASE4; 21 AE terms posted; arms: Metformin XR; Metformin IR)
- NCT00643851 — An Efficacy & Safety Study of BMS-512148 in Combination With Metformin Extended Release Tablets (N=994, PHASE3; 25 AE terms posted; arms: Dapagliflozin 5 mg + Metformin XR; Dapagliflozin 5 mg; Metformin XR)
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 |
|---|---|---|---|---|---|---|
| Lactic acidosis | 4,401 | 58.4 56.6–60.2ROR 63.2 · calibrated p 3e-6 ✓ | 50.4 EB05 49.2 · IC025 +5.6 3/3 methods agree | Labeled — boxed warning exact term | age-adj. PRR 45.9 · serious PRR 39.7 · 93% clinician | not reported in cached trials |
| Diarrhoea (diarrhea) | 4,253 | 2.4 2.4–2.5ROR 2.6 · calibrated p 0.789 | 2.4 EB05 2.4 · IC025 +1.2 3/3 methods agree | Labeled adverse reaction exact term | age-adj. PRR 1.9 · serious PRR 2.2 | NCT01864174: 22/285 (7.7%) on Metformin Extended-Release |
| Nausea | 3,473 | 1.6 1.6–1.7ROR 1.7 · calibrated p 0.746 | 1.6 EB05 1.6 · IC025 +0.6 | Labeled adverse reaction exact term | age-adj. PRR 1.4 · serious PRR 1.7 | NCT00643851: 8/201 (4.0%) on Metformin Extended-Release |
| Acute kidney injury (sudden kidney damage) | 3,123 | 7.7 7.4–7.9ROR 8.1 · calibrated p 0.065 | 7.5 EB05 7.3 · IC025 +2.9 3/3 methods agree | Labeled — boxed warning synonym match | age-adj. PRR 6.7 · serious PRR 5.9 | not reported in cached trials |
| Fatigue (tiredness) | 3,054 | 1.4 1.4–1.5ROR 1.5 · calibrated p 0.624 | 1.4 EB05 1.4 · IC025 +0.5 | Not in label — unassessed | age-adj. PRR 1.2 · serious PRR 1.4 | not reported in cached trials |
| Drug ineffective (drug did not work) | 2,722 | 0.8 0.7–0.8ROR 0.7 · calibrated p 0.155 | 0.8 EB05 0.7 · IC025 -0.5 PRR-only: not supported by EBGM or IC | Reporting / coding artifact | age-adj. PRR 0.8 · serious PRR 1.0 | not reported in cached trials |
| Dyspnoea (shortness of breath) | 2,602 | 1.7 1.6–1.8ROR 1.7 · calibrated p 0.787 | 1.7 EB05 1.6 · IC025 +0.7 | Not in label — unassessed | age-adj. PRR 1.4 · serious PRR 1.5 | not reported in cached trials |
| Vomiting | 2,585 | 2.0 2.0–2.1ROR 2.1 · calibrated p 0.988 | 2.0 EB05 2.0 · IC025 +1.0 | Labeled adverse reaction exact term | age-adj. PRR 2.0 · serious PRR 2.0 | not reported in cached trials |
| Headache | 2,252 | 1.3 1.3–1.4ROR 1.3 · calibrated p 0.533 | 1.3 EB05 1.3 · IC025 +0.3 | Labeled adverse reaction exact term | age-adj. PRR 1.2 · serious PRR 1.4 | not reported in cached trials |
| Off label use (used outside approved label) | 2,130 | 0.9 0.9–0.9ROR 0.9 · calibrated p 0.242 | 0.9 EB05 0.9 · IC025 -0.2 PRR-only: not supported by EBGM or IC | Reporting / coding artifact | age-adj. PRR 0.9 · serious PRR 1.0 | not reported in cached trials |
| Dizziness | 2,075 | 1.5 1.5–1.6ROR 1.6 · calibrated p 0.678 | 1.5 EB05 1.5 · IC025 +0.5 | Labeled adverse reaction exact term | age-adj. PRR 1.3 · serious PRR 1.6 | not reported in cached trials |
| Asthenia (weakness) | 2,065 | 2.0 1.9–2.1ROR 2.1 · calibrated p 0.979 | 2.0 EB05 1.9 · IC025 +0.9 | Not in label — unassessed | age-adj. PRR 1.7 · serious PRR 1.9 | not reported in cached trials |
| Pain | 2,013 | 1.2 1.2–1.3ROR 1.2 · calibrated p 0.448 | 1.2 EB05 1.2 · IC025 +0.2 | Labeled — boxed warning exact term | age-adj. PRR 1.3 · serious PRR 1.1 | NCT01864174: 1/285 (0.4%) on Metformin Extended-Release (serious AE) |
| Fall | 1,879 | 2.1 2.0–2.2ROR 2.1 · calibrated p 0.991 | 2.1 EB05 2.0 · IC025 +1.0 3/3 methods agree | Labeled adverse reaction exact term | age-adj. PRR 1.7 · serious PRR 1.8 | not reported in cached trials |
| Malaise (feeling unwell) | 1,772 | 1.5 1.4–1.6ROR 1.5 · calibrated p 0.642 | 1.5 EB05 1.4 · IC025 +0.5 | Labeled — boxed warning exact term | age-adj. PRR 1.5 · serious PRR 1.6 | 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.
- Heart sounds — n=40, PRR 258.5
- Pulmonary vasculitis — n=114, PRR 101.1
- Neurologic neglect syndrome — n=113, PRR 93.0
- Prolonged expiration — n=40, PRR 65.5
- Total lung capacity abnormal — n=55, PRR 62.0
- Hypocholesterolaemia — n=44, PRR 61.3
- Capillaritis — n=38, PRR 60.6
- Carotid artery thrombosis — n=118, PRR 58.9
- Alveolar osteitis — n=54, PRR 53.3
- Urinary tract discomfort — n=56, PRR 51.8
✓ 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 Extended-Release?
In FDA FAERS, the most frequently co-reported reaction terms for Metformin Extended-Release are lactic acidosis, diarrhoea, nausea, acute kidney injury, fatigue, dyspnoea. 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 Extended-Release have an FDA boxed warning?
Yes. The current FDA label carries a boxed warning: LACTIC ACIDOSIS Post-marketing 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 Extended-Release 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 96c8a89d-99db-24b1-e053-2a95a90ac2b8, effective 20260625; matched on
openfda.generic_name.exact:"METFORMIN HYDROCHLORIDE EXTENDED-RELEASE TABLETS") - 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, 1,204 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 EXTENDED-RELEASE, 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.