Bedside Snapshot

Use It For
Type 2 diabetes in adults and children ≥10 yr; diabetes prevention in high-risk prediabetes (off-label). Acute care: a home drug to hold in shock, sepsis or AKI, and the cause of MALA
Adult Dose
  • IR: 500 mg PO twice daily with meals, increase by 500 mg weekly (max 2,550 mg/day)
  • ER: 500 mg PO once daily with the evening meal, increase by 500 mg weekly (max 2,000 mg/day)
Pediatric Dose
Age ≥10 yr: 500 mg PO twice daily with meals, increase by 500 mg weekly (max 2,000 mg/day). Not established under 10 yr; ER not established in children
Onset / Duration
IR: peak 2–3 hr / about 12 hr per dose; ER: peak 4–8 hr / 24 hr per dose; IR steady state in 24–48 hr
Do Not Give / Hold If
eGFR <30; metabolic acidosis or DKA; shock, sepsis, hypoxemia or AKI; NPO or day of surgery; iodinated contrast with AKI, eGFR below 30 or an arterial catheter study
Watch For
MALA: vomiting, abdominal pain, tachypnea, hypothermia, hypotension, lactate >5 mmol/L with anion gap; hypoglycemia with insulin or a sulfonylurea; low B12 on long-term use
Reversal / Rescue
No antidote. MALA: stop metformin, supportive care, prompt hemodialysis (FDA). EXTRIP: dialyze for lactate >20 mmol/L, pH ≤7.0, shock or failed care; lower bar if kidneys are impaired. Poison Help 1-800-222-1222
Must Remember
Think MALA in any sick metformin user with an anion gap acidosis, even with sepsis: send lactate and a blood gas, and call nephrology early, because hemodialysis clears the drug and corrects the acidosis

Indications

Emergency & Prehospital

  • Home medication with acute-care consequences: find it, combination tablets included. Look for it in any patient with vomiting, sepsis, shock, AKI or an anion gap acidosis
  • Metformin overdose or metformin-associated lactic acidosis (MALA): spot it early. Definitive care is hospital supportive care and hemodialysis

ED / ICU / Transport

  • Hold decisions on admission: shock, sepsis, hypoxemia, AKI, NPO status, surgery and iodinated contrast are the cases to weigh a hold for. Insulin is the preferred glucose-lowering therapy for most hospitalized patients (see insulin)

Other Uses

  • Type 2 diabetes in adults: effective, inexpensive and weight-neutral. Alone, it does not cause hypoglycemia. It is usually continued when insulin is added. ASCVD, heart failure or CKD also call for an agent with proven cardiorenal benefit
  • Type 2 diabetes in children 10 yr and older: first-line when insulin is not needed at diagnosis (IR tablets and oral solution).
  • Prediabetes at high risk of progression: diabetes prevention, not treatment. It is aimed especially at age 25–59 yr with BMI ≥35 kg/m², higher fasting glucose (e.g. ≥110 mg/dL) and higher A1C (e.g. ≥6.0%), and at people with prior gestational diabetes (off-label)
  • Drug-induced hyperglycemia: consider it to prevent hyperglycemia in high-risk patients on high-dose glucocorticoids or a PI3Kα inhibitor (e.g. alpelisib). For hyperglycemia from mTOR or PI3Kα inhibitors, it is the first-line treatment (off-label)
  • Polycystic ovary syndrome (PCOS): add it to lifestyle change and it improves menstrual regularity and hyperandrogenism. Ovulation induction is off-label
  • Gestational or pregestational type 2 diabetes: insulin comes first. Metformin is the second-line alternative after counseling (off-label in pregnancy)

Dosing & Administration

These are the FDA-label doses. The renal limits differ from the label, and you'll find them under Special Populations.

Available Forms

  • Immediate-release (IR) tablets: 500 mg, 850 mg and 1,000 mg
  • Extended-release (ER) tablets: 500 mg and 750 mg (some products 1,000 mg). Swallow whole. Never crush, cut or chew
  • Oral solution: 100 mg/mL (500 mg per 5 mL). Measure it with the product’s dosing cup
  • Combination tablets: metformin with a DPP-4 inhibitor (e.g. sitagliptin), a sulfonylurea (e.g. glipizide), an SGLT2 inhibitor (e.g. dapagliflozin) or pioglitazone
  • EMS / transport: not carried. Record the product, strength and last dose as a home medication

Adult Dosing

IndicationDose & RouteRepeat / MaxNotes
Type 2 diabetes: IR tablets
500 mg PO twice daily with meals, or 850 mg PO once daily with a meal
Increase by 500 mg weekly or 850 mg every 2 weeks; max 2,550 mg/day in divided doses
Fixed dose, not weight-based. Doses above 2,000 mg/day may be better tolerated three times daily with meals
Type 2 diabetes: ER tablets
500 mg PO once daily with the evening meal
Increase by 500 mg weekly; max 2,000 mg/day
Switch from IR at the same total daily dose. Not controlled on 2,000 mg once daily: try 1,000 mg twice daily; higher needs: switch to IR. ER products differ (some start at 1,000 mg or allow up to 2,500 mg/day): follow the product’s labeling. Missed dose: do not double

Pediatric Dosing

IndicationDose (per kg) & RouteMax Single / Max TotalNotes
Type 2 diabetes, age ≥10 yr
500 mg PO twice daily with meals (IR tablet or 5 mL of 100 mg/mL solution); fixed dose, not per kg
Increase by 500 mg weekly; max 2,000 mg/day in 2 divided doses
First-line when A1C is <8.5% and the patient is asymptomatic, without ketosis or acidosis
Type 2 diabetes with marked hyperglycemia (A1C ≥8.5% or random glucose ≥250 mg/dL), or ketosis/DKA
Marked hyperglycemia without acidosis: long-acting (basal) insulin while metformin is started and titrated. Ketosis or DKA: subcut or IV insulin first; start metformin once acidosis resolves
Same titration; max 2,000 mg/day
Never start metformin during ketoacidosis. Taper insulin once glycemic goals are met
Age <10 yr, or ER tablets at any pediatric age
Not established in children
Not established
Use IR tablets or oral solution from age 10; pediatric endocrinology guides younger patients

Preparation & Administration

  • With food: IR with meals, ER with the evening meal. Food and slow titration reduce GI upset
  • Renal thresholds: the eGFR-based starting, dose-limit and stop rules sit in Special Populations
  • Restarting after a hold: restart once the patient is eating and drinking, hemodynamically stable and eGFR is stable (48 hr after contrast in at-risk patients)

Contraindications & Precautions

Contraindications

  • Severe renal impairment: eGFR <30 mL/min/1.73 m²
  • Acute or chronic metabolic acidosis, including diabetic ketoacidosis (DKA)
  • Hypersensitivity to metformin

Precautions

  • eGFR 30–44: keep the dose at 1,000 mg/day or less (see Special Populations). The FDA label differs. It does not recommend starting at 30–45
  • Hepatic disease: avoid it. Poor lactate clearance raises MALA risk
  • Hypoxic or low-flow states: acute heart failure with hypoperfusion, shock, acute MI, sepsis
  • Excess alcohol: it strengthens metformin’s effect on lactate
  • Age ≥65 yr: expect more renal, hepatic and cardiac impairment. Check eGFR more often
  • Mitochondrial disease (MELAS, maternally inherited diabetes and deafness): not recommended
  • Iodinated contrast: No hold and no renal recheck for IV contrast at eGFR 30 or above with no AKI (ACR). When there is AKI, eGFR below 30 or an arterial catheter study with possible renal emboli, hold at the time of the procedure and for 48 hours. Restart only once renal function is re-evaluated and normal. Usual-dose gadolinium: no hold. The FDA label differs, saying hold for eGFR 30 to 60, liver disease, alcoholism, heart failure or intra-arterial contrast.

Hold / Reassess If

  • Shock, sepsis, hypoxemia, acute heart failure with hypoperfusion, or AKI: hold
  • Restricted food and fluids (NPO, persistent vomiting) and the day of surgery or a procedure: hold
  • Lactate >5 mmol/L or an unexplained anion gap acidosis: stop and evaluate for MALA
  • eGFR falls below 45: reassess benefit and risk and limit the dose; below 30: stop
FDA Boxed Warning: Metformin-associated lactic acidosis can kill. Hypothermia, hypotension and resistant bradyarrhythmias come with it. Renal impairment, carbonic anhydrase inhibitors, age ≥65, contrast studies, surgery, hypoxic states, excess alcohol, hepatic impairment and mitochondrial disease all raise the risk. Suspect it? Stop metformin, start supportive care in hospital and arrange prompt hemodialysis.

Adverse Effects & Toxicity

Common

  • Diarrhea: 53% with IR (12% placebo); 10% with ER
  • Nausea or vomiting: 26% with IR; 7% with ER
  • Flatulence, indigestion, abdominal discomfort: 6–12% with IR
  • Asthenia and headache: 6–9% with IR
  • Taste disturbance: 1–5%
  • Low vitamin B12: about 7% of patients fell to subnormal levels in 29-week trials

Serious / Life-Threatening

EffectRecognitionManagement
Lactic acidosis (MALA)
Malaise, myalgias, abdominal pain, somnolence, tachypnea; later hypothermia, hypotension, bradyarrhythmias. Lactate >5 mmol/L, anion gap acidosis without ketones
Stop metformin, treat shock and sepsis, prompt hemodialysis (Overdose below)
Hypoglycemia (with insulin or a sulfonylurea)
Low point-of-care glucose, diaphoresis, confusion, seizure
Oral glucose if awake; IV dextrose or glucagon if not; lower the co-agent dose
Vitamin B12 deficiency
Anemia, new or worsening peripheral neuropathy
Check B12 and CBC; replete
Liver injury (postmarketing)
Cholestatic, hepatocellular or mixed pattern on liver tests
Stop metformin and evaluate

Overdose & Toxicity Management

  • Presentation: ingestions over 50 g are reported. Lactic acidosis occurs in about 32% of overdoses. Hypoglycemia occurs in about 10%, and causation is not proven. MALA can look like sepsis or mesenteric ischemia
  • Immediate care: airway, breathing, circulation; check glucose, lactate, blood gas, electrolytes with anion gap and creatinine; treat sepsis, hypoxia and shock (MAP ≥65 mmHg). Call Poison Help (1-800-222-1222) or a medical toxicologist
  • Combination tablet with a sulfonylurea: hypoglycemia can return after the patient seems to recover. Give IV dextrose, keep glucose above 100 mg/dL and monitor at least 24–48 hr. Recurrent or refractory hypoglycemia: add octreotide alongside dextrose with toxicology or Poison Center advice. Commonly reported doses are 50–100 mcg subcut every 6–8 hr in adults and about 1 mcg/kg IV in children (protocol-dependent)
  • Pediatric exploratory ingestion: identify the exact product. A child who swallowed any sulfonylurea-containing combination tablet needs observation. Serial glucose checks catch delayed hypoglycemia, per Poison Center advice
  • Activated charcoal: metformin alone gives it no role. After a sulfonylurea-containing combination tablet it may be appropriate, if the airway is intact or protected, with Poison Center or toxicology advice
  • Sodium bicarbonate: may buy time in profound acidemia (pH ≤7.2). It does not remove metformin, and it does not replace dialysis (see sodium bicarbonate)
  • Extracorporeal removal (EXTRIP): recommended for lactate >20 mmol/L, pH ≤7.0, shock, or failure of standard care. Suggested for lactate 15–20 mmol/L, pH 7.0–7.1 or decreased consciousness. Set the bar lower when impaired kidney function or liver failure limits metformin clearance. Intermittent hemodialysis comes first. CRRT is the choice if hemodialysis is unavailable. Continue until lactate <3 mmol/L and pH >7.35, then watch for rebound.
  • Antidote: there is none for metformin. The death rate is about 30% in the severe poisonings EXTRIP reviewed, about 11–17% in recent MALA case series and ICU cohorts, and up to 36% at 30 days in one hospital cohort

Monitoring
ParameterWhen / How OftenTarget / Act If
Clinical: GI tolerance
Each titration step
Persistent diarrhea or vomiting: slow titration, give with food or switch to ER; poor oral intake: hold
Clinical: hypoglycemia
Glucose checks per the diabetes plan when combined with insulin or a sulfonylurea; any altered mental status
Glucose <70 mg/dL: treat, then lower the insulin or sulfonylurea dose
Laboratory: A1C
Every 3 months while titrating or not at goal; at least twice yearly once stable at goal
Above the individual goal: titrate or add an agent per the diabetes plan
Laboratory: eGFR
Before starting; at least yearly; every 3–6 months once eGFR is <60; more often in older adults
eGFR <45: reassess and limit dose; <30: stop
Laboratory: creatinine in acute illness
On admission; with sepsis, dehydration or before contrast
Rising creatinine or AKI: hold until renal function recovers
Laboratory: lactate, blood gas, anion gap
Any metformin user with vomiting, tachypnea, hypotension, hypothermia or altered mental status
Lactate >5 mmol/L with anion gap acidosis: stop; involve nephrology and toxicology for hemodialysis
Laboratory: vitamin B12 and CBC
B12 every 2–3 years and CBC yearly on long-term therapy; sooner with anemia or neuropathy
Low B12 or anemia: replete and evaluate
Drug level: metformin
If available, to support a MALA diagnosis
Usually >5 mcg/mL in MALA; a low level does not exclude it; never delay dialysis for a level
After contrast
eGFR 48 hr after iodinated contrast in patients who held metformin
Stable renal function: restart
After hemodialysis
Serial lactate and pH
Rebound acidosis: repeat hemodialysis or CRRT

Interactions & Compatibility

Clinically Significant Interactions

Drug / ClassEffectWhat To Do
Iodinated contrast
Contrast-associated AKI can cause metformin accumulation and MALA
No hold with IV contrast at eGFR 30 or above and no AKI, per ACR guidance. Hold for AKI, eGFR below 30 or an arterial catheter study; restart only after renal function is re-evaluated and normal (48 hr). Differs from FDA label, which also holds for eGFR 30 to 60
Carbonic anhydrase inhibitors (topiramate, zonisamide, acetazolamide, dichlorphenamide)
Non-anion gap acidosis; higher lactic acidosis risk
Monitor bicarbonate and anion gap more often
OCT2/MATE inhibitors (ranolazine, vandetanib, dolutegravir, cimetidine)
Reduced renal clearance; higher metformin levels
Weigh benefit and risk; monitor for MALA
Alcohol
Potentiates metformin’s effect on lactate
Avoid excess intake; consider MALA in an intoxicated, acidotic patient
Insulin and sulfonylureas
Hypoglycemia
Lower the insulin or sulfonylurea dose; check glucose
Drugs that raise glucose (corticosteroids, thiazides, phenothiazines, thyroid products, estrogens, sympathomimetics)
Loss of glycemic control; hypoglycemia when stopped
Monitor glucose when starting or stopping
Drugs that impair renal function or perfusion (NSAIDs, aminoglycosides, IV vancomycin, diuretics with an ACE inhibitor or ARB)
Metformin accumulation
Monitor eGFR more often

Oral only. No IV formulation exists, so IV compatibility is not a question.

Special Populations
  • Pediatrics: From age 10 yr, IR tablets and oral solution are approved. ER is not established in children. Adverse effects match adults. The doses sit in the Pediatric Dosing table.
  • Pregnancy: The published data show no clear link to major birth defects or miscarriage. Still, metformin crosses the placenta, and cord levels run as high as maternal levels. Some studies show higher childhood BMI after exposure. Insulin is preferred for gestational and type 2 diabetes. Metformin is an alternative after counseling. Avoid it with hypertension, preeclampsia or risk of intrauterine growth restriction. Stop metformin used for PCOS by the end of the first trimester.
  • Lactation: It is present in milk. The infant dose is about 0.11–1% of the maternal weight-adjusted dose. Weigh breastfeeding benefits against the limited infant data.
  • Older Adults: Age-related renal, hepatic and cardiac decline raises MALA risk. Start low and check eGFR more often.
  • Renal Impairment: Metformin is recommended at eGFR 30 or above. At eGFR 30 to 44, reduce the dose to 1,000 mg/day maximum (KDIGO 2022 Recommendation 4.1.1, 1B; ADA/KDIGO 2022 consensus). Stop below eGFR 30 and on dialysis. This differs from the FDA label and ADA 2026: do not start at eGFR 30 to 44. When eGFR falls below 45, reassess benefit and risk. Consider a lower dose at 45–59 when lactic acidosis risk is high. Once below 60, check eGFR every 3–6 months.
  • Hepatic Impairment: Avoid it with clinical or laboratory evidence of liver disease.
  • Obesity / Dosing Weight: Doses are fixed. There is no weight adjustment.
  • Mitochondrial Disease: Not recommended in MELAS or maternally inherited diabetes and deafness. Stop if lactate rises.
  • Anovulatory Women: Ovulation can resume on metformin. Talk through the chance of unintended pregnancy.
  • Hospitalized and Surgical Patients: Insulin is preferred for most inpatient hyperglycemia. Hold metformin on the day of surgery or a procedure, and while intake is restricted.

Clinical Pearls
MALA Hides Behind Sepsis: Early MALA looks vague: malaise, vomiting, abdominal pain. It can mimic sepsis or mesenteric ischemia. It often coexists with hypoperfusion, so a septic picture does not rule it out. Check lactate and the anion gap in every sick metformin user.
Exam Discriminator, Type A vs Type B Lactic Acidosis: Type A is tissue hypoperfusion: shock, hypoxia. Type B happens without hypoperfusion, and metformin is the classic drug cause. MALA is type B, but it often mixes with type A.
Check Ketones on SGLT2 Combinations: A metformin-SGLT2 inhibitor tablet (e.g. dapagliflozin-metformin) puts euglycemic DKA on the anion gap list. Send beta-hydroxybutyrate with the lactate. Glucose can sit near normal while DKA and MALA coexist.
Metformin Alone Rarely Drops Glucose: Low glucose on metformin points to insulin, a sulfonylurea (including a combination tablet) or another illness. Read the full product name on the bottle.
Contrast and Metformin: With IV contrast, eGFR 30 or above and no AKI, you need no hold and no recheck. Hold at the time of the procedure and for 48 hours when there is AKI, eGFR below 30, or an arterial catheter study with possible renal emboli. Restart only after renal function is re-evaluated and normal. Usual-dose gadolinium: no hold. This differs from the FDA label, which says hold for eGFR 30 to 60, liver disease, alcoholism, heart failure or intra-arterial contrast.
Own the Restart: A hold for AKI, contrast or surgery is temporary. Write the restart criteria (eating, stable hemodynamics, stable eGFR) into the handoff or discharge orders. That way the patient does not lose first-line therapy by accident.
Try Before Abandoning: Most GI intolerance eases with slower titration, dosing with food or switching to the ER form. Try those before you abandon it.
B12 and Neuropathy: Long-term metformin user with neuropathy or anemia? Check B12 before you blame diabetes alone. Metformin lowers B12, and that can worsen neuropathy symptoms.

Pharmacology

Mechanism of Action

  • Cuts hepatic glucose production, so fasting glucose falls
  • Slows intestinal glucose absorption and boosts peripheral glucose uptake (better insulin sensitivity), so postprandial glucose falls
  • It does not raise insulin secretion, so hypoglycemia is minimal when used alone
  • Cuts hepatic lactate uptake, so lactate rises. That rise is the basis of MALA when the drug builds up

Pharmacokinetics

RouteOnsetPeakDuration
PO, IR
Steady state in 24–48 hr
2–3 hr (food delays it about 35 min)
About 12 hr per dose (twice-daily dosing)
PO, ER
No accumulation with repeated doses
4–8 hr (median 7 hr)
24 hr per dose (once-daily dosing)
  • Bioavailability: 50–60% (IR, fasting). Absorption is less than dose-proportional
  • Half-life: plasma about 6.2 hr. Whole blood about 17.6 hr in the red-cell compartment. Both run longer in renal impairment
  • Metabolism: none. No metabolites in humans
  • Elimination: renal, mainly tubular secretion. Renal clearance is about 3.5 times creatinine clearance. About 90% goes within 24 hr
  • Protein binding / Vd: negligible binding. Vd about 650 L. Dialyzable, with clearance up to 170 mL/min

Names & Classification
Generic Name
Metformin hydrochloride
Brand Names
Glucophage, Glucophage XR, Fortamet, Glumetza, Riomet (oral solution); Drugs@FDA lists these brands as discontinued, and US supply is mainly generic. Combination products include Janumet (sitagliptin) and generic glipizide-metformin and dapagliflozin-metformin
Pharmacologic Class
Biguanide
Therapeutic Class
Oral antihyperglycemic (antidiabetic)
Controlled Substance
Not controlled
ISMP High-Alert
No (the ISMP acute-care list names oral sulfonylureas and insulin, not metformin)
Look-Alike / Sound-Alike
Many combination tablets contain metformin; confirm the full product name and every ingredient at reconciliation

Related

References
  1. Laurus Labs Limited. (2026). Metformin hydrochloride tablets and metformin hydrochloride extended-release tablets: Prescribing information (boxed warning revised 3/2026). DailyMed, U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c3dfa8a1-d10a-4a1a-8eba-5f4e2a5a2949; and Micro Labs Limited. (2026). Metformin hydrochloride oral solution: Prescribing information. DailyMed, U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=fb90693a-074a-45be-94f4-ed6298b1f4e4; and Teva Pharmaceuticals USA. (2026). Glipizide and metformin hydrochloride tablets: Prescribing information (overdosage). DailyMed, U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=03d9ce02-0559-494c-a53d-de9b9a64b606
  2. American Diabetes Association Professional Practice Committee for Diabetes. (2026). Standards of Care in Diabetes—2026. Diabetes Care, 49(Suppl. 1): 3. Prevention or delay of diabetes and associated comorbidities, S50–S60, https://doi.org/10.2337/dc26-S003; 6. Glycemic goals, hypoglycemia, and hyperglycemic crises, S132–S149, https://doi.org/10.2337/dc26-S006; 9. Pharmacologic approaches to glycemic treatment, S183–S215, https://doi.org/10.2337/dc26-S009; 11. Chronic kidney disease and risk management, S246–S260, https://doi.org/10.2337/dc26-S011; 13. Older adults, S277–S296, https://doi.org/10.2337/dc26-S013; 14. Children and adolescents, S297–S320, https://doi.org/10.2337/dc26-S014; 15. Management of diabetes in pregnancy, S321–S338, https://doi.org/10.2337/dc26-S015; 16. Diabetes care in the hospital, S339–S355, https://doi.org/10.2337/dc26-S016
  3. de Boer, I. H., Khunti, K., Sadusky, T., et al. (2022). Diabetes management in chronic kidney disease: A consensus report by the American Diabetes Association (ADA) and Kidney Disease: Improving Global Outcomes (KDIGO). Diabetes Care, 45(12), 3075–3090. https://doi.org/10.2337/dci22-0027; and Kidney Disease: Improving Global Outcomes (KDIGO) Diabetes Work Group. (2022). KDIGO 2022 clinical practice guideline for diabetes management in chronic kidney disease. Kidney International, 102(5S), S1–S127. https://doi.org/10.1016/j.kint.2022.06.008
  4. ACR Committee on Drugs and Contrast Media. (2026). ACR manual on contrast media (Metformin chapter). American College of Radiology. https://www.acr.org/Clinical-Resources/Clinical-Tools-and-Reference/Contrast-Manual
  5. Calello, D. P., Liu, K. D., Wiegand, T. J., et al. (2015). Extracorporeal treatment for metformin poisoning: Systematic review and recommendations from the Extracorporeal Treatments in Poisoning Workgroup (landmark consensus). Critical Care Medicine, 43(8), 1716–1730. https://doi.org/10.1097/CCM.0000000000001002
  6. See, K. C. (2024). Metformin-associated lactic acidosis: A mini review of pathophysiology, diagnosis and management in critically ill patients. World Journal of Diabetes, 15(6), 1178–1186. https://doi.org/10.4239/wjd.v15.i6.1178
  7. Hoegberg, L. C. G., Gosselin, S., Buckley, N. A., et al. (2026). Recommendations from the Clinical Toxicology Recommendations Collaborative on the administration of activated charcoal in acute oral overdose. Clinical Toxicology, 64(6), 419–475. https://doi.org/10.1080/15563650.2025.2609807
  8. Ryan, E., & Rushton, W. (2025). Variations in octreotide dosing in published reports of sulfonylurea toxicity: A systematic review, 1988–present. Journal of Medical Toxicology, 21(2), 260–275. https://doi.org/10.1007/s13181-024-01054-5

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