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Metformin poisoning
Authors: Jason Chu, MD, Andrew Stolbach, MD, MPH, FAACT, FACMT, FACEP
Section Editor: Stephen J Traub, MD
Deputy Editor: Jonathan Grayzel, MD, FAAEM

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Jun 2021. | This topic last updated: Jul 23, 2020.

INTRODUCTION

In normal individuals, fasting plasma glucose levels range from about 60 to 100 mg/dL (3.3 to 5.6 mmol/L) [1]. In patients with diabetes mellitus, insulin deficiency or insulin resistance leads to a state
of hyperglycemia. Galega officinalis (goat's rue or French lilac) was used to treat diabetes in medieval Europe. The active ingredient, guanidine, was used to synthesize other antidiabetic agents in the
1920s [2], and the biguanide hypoglycemic agents phenformin and metformin became available for clinical use in the 1950s.

Biguanides are antihyperglycemic agents, not hypoglycemic agents; they promote euglycemia but alone are unlikely to cause hypoglycemia. Biguanides are used both as monotherapy and in
combination with other oral hypoglycemic agents. They can exacerbate hypoglycemia caused by other types of antidiabetic medicines [3,4].

The major toxicity from acute or chronic biguanide use is lactic acidosis. The high rate of severe lactic acidosis from phenformin led to the withdrawal of this drug from the US market in 1976,
although it remains available in several countries. Metformin is the principal biguanide in clinical use.

The management of metformin toxicity is reviewed here. A summary table to facilitate emergent management is provided ( table 1). General issues relating to hypoglycemia, the therapeutic use of
biguanides, and the general clinical management of drug intoxication are presented separately. (See "Physiologic response to hypoglycemia in normal subjects and patients with diabetes mellitus"
and "Hypoglycemia in adults without diabetes mellitus: Diagnostic approach" and "Metformin in the treatment of adults with type 2 diabetes mellitus" and "General approach to drug poisoning in
adults".)

PHARMACOLOGY

Metformin decreases insulin resistance, decreases hepatic glucose output, and enhances peripheral glucose uptake [5]. Proposed mechanisms of action include enhanced suppression of
gluconeogenesis by insulin, reduced glucagon-stimulated gluconeogenesis, and increased uptake of glucose by muscle and adipose cells [5]. The net effects of these changes in diabetic patients are
to decrease fasting and post-prandial blood glucose by 20 to 40 percent, decrease hemoglobin A1C, decrease body weight slightly, decrease low density lipoprotein (LDL), and increase high density
lipoprotein (HDL) [6]. (See "Metformin in the treatment of adults with type 2 diabetes mellitus".)

KINETICS

Metformin absorption occurs primarily in the upper part of the intestine [7]. The drug has negligible plasma protein binding and a volume of distribution ranging from 63 to 276 L (1 to 5 L/kg) [6-8].
The elimination half-life of metformin in patients who take multiple doses and have good renal function is approximately five hours [7]. Metformin is excreted, unmetabolized, via transporters in the
proximal tubules of the kidneys, and may accumulate in acute and chronic kidney disease [9].

TOXICITY

The major toxicity of metformin is lactic acidosis, although it can contribute to hypoglycemia when in combination with other hypoglycemic drugs.

Lactic acidosis

Mechanism — The mechanism of metformin-associated lactic acidosis is complex. Metformin promotes the conversion of glucose to lactate in the splanchnic bed of the small intestine [10].
Metformin also inhibits mitochondrial respiratory chain complex 1, leading to decreased hepatic gluconeogenesis from lactate, pyruvate, and alanine [11]. This results in additional lactate and
substrate for lactate production [12].

While some authors use the term "metformin-induced" lactic acidosis (rather than "metformin-associated") to distinguish the condition where metformin is clearly responsible, making this distinction
may require obtaining a metformin concentration, which is not readily available [13]. More importantly, the distinction does not alter management.

Incidence — In the absence of acute overdose, metformin-associated lactic acidosis rarely develops in patients without comorbidities such as kidney or hepatic insufficiency or acute infection. A
systematic review of 347 trials and cohort studies revealed no cases of fatal or nonfatal lactic acidosis in 47,846 patient-years of metformin use and calculated the upper limit of the incidence of such
lactic acidosis to be 4.3 cases per 100,000 patient years [14]. (See "Causes of lactic acidosis", section on 'Diabetes mellitus'.)

However, in the rare circumstance when metformin-associated lactic acidosis develops, mortality is high. This has been reported in multiple case series [11,13,15,16]. In one case series of 49
metformin-treated patients, mortality was 45 percent [15]. Neither arterial lactate levels nor plasma metformin concentrations predicted mortality. Death in these patients more closely correlated
with underlying comorbid conditions. Another case series of 42 patients reported a mortality rate of 48 percent among patients with unintentional metformin poisoning [16]. In this study, the most
accurate predictor of death was liver dysfunction, as demonstrated by an elevated prothrombin time. In a case series of 66 patients with metformin associated lactic acidosis, metformin
concentrations correlated with creatinine and lactate levels, although the absolute metformin and lactate concentrations were not different in survivors and non-survivors [11].

Metformin-associated lactic acidosis may occur following acute overdose [17-22]. In one case series, 11 of 13 patients with an acute overdose had elevated lactate levels [23]. A systematic review of
studies involving confirmed acute metformin overdose found that lower serum pH and higher serum lactate concentrations correlated with increased mortality [24]. In this review, all 16 survivors had
a serum pH above 6.9 and a serum lactate below 25 mmol/L, while 5 of the 6 patients with a pH below 6.9 or a lactate above 25 mmol/L died.

Risk factors — Because reports of dosages in overdose are often unreliable, it is unclear what minimum dose of metformin leads to toxicity. The clinician should have a high index of suspicion for
toxicity in children who ingest more than one or two tablets, anyone who presents with intentional overdose, and patients with comorbidities such as acute or chronic kidney disease, liver disease, or
heart failure.

Clinically significant lactic acid accumulation almost always occurs in the presence of comorbid conditions, such as the following:

● Impaired kidney function (precise thresholds vary; details are provided separately (see "Metformin in the treatment of adults with type 2 diabetes mellitus", section on 'Contraindications'))

● Concurrent liver disease

● Active alcohol abuse

 ● Unstable or acute heart failure

● History of lactic acidosis during metformin therapy

● Decreased tissue perfusion or hemodynamic instability

● Hypoxic states or serious acute illness

HISTORY AND PHYSICAL EXAMINATION

In the setting of acute overdose, clinicians should seek information about dose and coingestants, although such information is frequently unreliable. Whether the patient has an acute overdose or
chronic toxicity, clinicians should also ask whether other antidiabetic agents are used.

Patients with metformin overdose may complain of nausea and abdominal pain [18,22,25]. In the setting of chronic metformin use and lactic acidosis accumulation (metformin associated lactic
acidosis [MALA]), the most common complaints are gastrointestinal, including nausea, vomiting, and diarrhea, followed by altered mental status and shortness of breath [11]. Physical examination
findings may include tachycardia, hypotension, and tachypnea in patients with severe lactic acidosis. Alterations in mental status may be due to acidosis or hypoglycemia [18,22,25], although the
latter is uncommon without concurrent use of a hypoglycemic agent.

LABORATORY EVALUATION

Studies to obtain — Routine laboratory evaluation of any acutely poisoned patient should include the following:

● Fingerstick glucose, to rule out hypoglycemia as the cause of any alteration in mental status; this is particularly important in patients in whom metformin toxicity is suspected, and in diabetics
generally

● Acetaminophen and salicylate levels, to rule out these common coingestions

● Electrocardiogram, to rule out conduction system poisoning by coingestants that affect the QRS or QTc intervals

● Pregnancy test in women of childbearing age

Specific laboratory testing in cases of known or suspected metformin toxicity should include the following:

● Arterial or venous blood gas, for accurate determination of the patient's acid-base status

● Basic chemistries, to determine the bicarbonate concentration and to assess kidney function

● Serum lactate level, to confirm that any metabolic acidosis is in fact a lactic acidosis

Metformin concentration — Obtaining a serum metformin concentration is unhelpful in most cases because few hospitals perform the test and thus timely results are rarely available, and because
the serum concentration often does not correlate with the severity of the poisoning or patient outcome [11,15,24,26]. An undetectable concentration excludes metformin as the cause of lactic
acidosis in most cases. Nevertheless, it is important to consider other causes of lactic acidosis (eg, sepsis, bowel ischemia) in patients who take metformin.

MANAGEMENT OF OVERDOSE OR TOXICITY

The following treatment recommendations are based upon our clinical experience and the limited available evidence. A summary table to facilitate emergent management is provided ( table 1).

Airway, breathing, circulation — Victims of acute or chronic metformin toxicity rarely require endotracheal intubation. It is important to note that hyperpnea and tachypnea may reflect
compensation for a metabolic acidosis and may not represent impending respiratory failure. If intubation is required, the clinician should pay special attention to ventilator management. Minute
ventilation sufficient to compensate for any underlying acidosis should be maintained and arterial blood gas results checked frequently until the patient is stabilized. (See "Simple and mixed acid-
base disorders".)

Hypotension should initially be treated with intravenous fluids, followed by vasopressors if needed. Persistent hypotension suggests profound toxicity, and in such cases hemodialysis treatment is
often necessary. (See 'Extracorporeal removal' below.)

Gastrointestinal decontamination — Gastrointestinal (GI) decontamination with activated charcoal (AC) is suggested in patients with acute metformin ingestion, unless specific contraindications
(such as bowel obstruction or GI perforation) exist. Patients with toxicity from chronic use are unlikely to benefit from GI decontamination. The clinician must assess aspiration risk, including mental
status and ability to protect the airway, in all patients before any attempts to administer AC. (See "Gastrointestinal decontamination of the poisoned patient", section on 'Activated charcoal'.)

Hypoglycemia — If hypoglycemia is present, it should be treated with 0.5 to 1 g/kg IV dextrose, followed by a meal if food is not contraindicated. Metformin alone should not cause hypoglycemia
and other causes should be sought. The acute management of hypoglycemia in children is discussed separately. (See "Diagnostic approach to hypoglycemia in infants and children".)

Lactic acidosis

Sodium bicarbonate — The use of sodium bicarbonate in metformin-induced lactic acidosis is controversial. If severe metabolic acidosis is present, sodium bicarbonate may be administered, but
there are theoretical disadvantages to its use [25]. These disadvantages include leftward shift of the hemoglobin dissociation curve, excess sodium load, rebound metabolic alkalosis, disturbances in
serum potassium and calcium, decreased myocardial contractility, increased carbon dioxide production, and reflex vasodilation after bolus injection [22]. (See "Bicarbonate therapy in lactic acidosis".)

Extrapolating from other clinical scenarios, we suggest limiting the use of sodium bicarbonate to patients with severe metabolic acidosis (arterial pH below 7.1, or below 7.2 in patients with severe
acute kidney injury), with the aim being to maintain the pH above 7.1 (or above 7.3 in patients with severe acute kidney injury), until the acute toxicity resolves.

Extracorporeal removal — Hemodialysis has been used successfully in patients with metformin-associated lactic acidosis due to chronic use or acute overdose [8,25,27,28]. We largely concur with
the findings and suggestions of the Extracorporeal Treatments in Poisoning Workgroup and recommend hemodialysis for patients with any of the following findings associated with severe
metformin poisoning from chronic use or acute overdose [8]:

● Severely elevated serum lactate concentration (>20 mmol/L)

● Severe metabolic acidosis (pH ≤7.0)

● Failure to improve (as determined by pH, lactate concentration, or clinical status) with supportive care and bicarbonate therapy within two to four hours.

Although evidence is limited, we suggest hemodialysis for patients with any of the following findings:

● Elevated serum lactate concentration between 15 to 20 mmol/L

 ● Metabolic acidosis (pH of 7.0 to 7.1)

● Comorbidities:

• Shock or persistent hemodynamic instability requiring vasopressor therapy despite acute administration of IV boluses of isotonic crystalloid totalling 30 mL/kg  

• Kidney injury – Creatine >2 mg/dL (adults), or >1.5 mg/dL (elderly), or 2 times upper limit of normal (children), or chronic kidney disease (stage 3b or higher with eGFR <45 mL/min/1.73 m2,
oliguria, or anuria)

• Liver failure – liver injury with coagulopathy (INR >1.5) and any degree of encephalopathy

• Decreased level of consciousness

For critically ill patients who do not meet any of the above criteria, (eg, those with lactate concentrations >15 mmol/L, or pH 7.0 to 7.1 ), or who have important comorbid conditions (eg, kidney
insufficiency, liver failure, decreased level of consciousness), it is important to obtain early consultation with a medical toxicologist and a nephrologist, and to coordinate care with these specialists, as
such patients may progress quickly to needing hemodialysis [8].

Hemodialysis should be performed using a bicarbonate buffer, as the benefits of hemodialysis lie in correcting the metabolic acidosis much more so than in removing metformin. Treatment may
need to be repeated should metabolic derangements recur. Hemodialysis may be discontinued when the lactate concentration is <3 mmol/L and the pH is >7.35 [8].

For patients with severe metformin poisoning requiring extracorporeal removal, hemodialysis is the preferred approach if the hemodynamics are adequate. Continuous hemodialysis (>15 hours) has
been used successfully in extremely ill patients. If the patient is hemodynamically unstable, CVVH or CVVHD should be considered. Continuous venovenous hemofiltration (CVVH) has been performed
in patients with metformin overdose [25,29]. According to case reports, the clearance of drug by CVVH was less than that generally reported to occur with conventional hemodialysis [27,29].
Therefore, CVVH should only be considered in patients who are too hemodynamically unstable to tolerate hemodialysis.

Although there are no randomized trials of prolonged renal replacement therapy in severe metformin poisoning, retrospective series and case reports support this approach when necessary [16,29-
31].

Antidote — There are no antidotes for metformin toxicity.

DISPOSITION

The onset of lactic acidosis may take several hours, so patients reporting an acute ingestion should be observed for at least six to eight hours [3,32]. Patients who are well appearing and who have a
normal acid-base status after six to eight hours may be discharged or transferred to the care of a psychiatrist.

If a patient deteriorates despite appropriate supportive care, the clinician should promptly consult nephrology regarding the possibility of hemodialysis. During this consultation, the clinician should
convey to the nephrologist both the patient's clinical condition and, if available, serial acid-base determinations to help document the patient's deterioration.

Patients may present with a mild lactate elevation or mildly increased anion gap, but have normal vital signs and an unremarkable physical examination. Such patients may be discharged home with
careful instructions to stop taking their metformin and to see their primary clinician within the next several days IF the laboratory abnormalities are minor and resolve on repeat evaluation after a
brief period (approximately six hours) of uneventful observation. Asymptomatic patients with persistent abnormalities (metabolic acidosis; elevated lactate) and symptomatic patients should be
observed using the same guidelines described for acute ingestions, or they should be admitted to the hospital for observation.

PEDIATRIC CONSIDERATIONS

The number of pediatric patients with Type II diabetes is increasing, likely as a result of the pediatric obesity epidemic. Metformin is one of only a few drugs approved for the treatment of Type II
diabetes in this population. It is logical to treat pediatric metformin toxicity in the same manner as one would treat adults, and anecdotal success supports such therapy [33,34]. (See "Management of
type 2 diabetes mellitus in children and adolescents".)

ADDITIONAL RESOURCES

Regional poison control centers in the United States are available at all times for consultation on patients who are critically ill, require admission, or have clinical pictures that are unclear (1-800-222-
1222). In addition, some hospitals have clinical and/or medical toxicologists available for bedside consultation and/or inpatient care. Whenever available, these are invaluable resources to help in the
diagnosis and management of ingestions or overdoses. Contact information for poison centers around the world is available at the website in the following reference [35].

SOCIETY GUIDELINE LINKS

Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: General measures for acute
poisoning treatment" and "Society guideline links: Treatment of acute poisoning caused by specific agents other than drugs of abuse".)

SUMMARY AND RECOMMENDATIONS

A summary table to facilitate emergent management of metformin intoxication is provided ( table 1).

● Biguanides are antihyperglycemic agents, not hypoglycemic agents; they promote euglycemia but taken alone are unlikely to cause hypoglycemia. Metformin absorption occurs primarily in the
intestine, and the drug is excreted unmetabolized from the kidneys. It may accumulate in renal failure. (See 'Pharmacology' above and 'Kinetics' above.)

● Lactic acidosis is the major toxicity of metformin and is associated with high mortality. Metformin-associated lactic acidosis may occur in patients with renal insufficiency, liver disease,
hemodynamic instability, or others in whom high levels of the drug accumulate. In such patients, mortality correlates with the severity of the underlying medical conditions and appears to be
increased in the setting of liver dysfunction. Lactic acidosis may also occur in acute metformin overdose. Among these patients, death correlates with high plasma lactate and low serum pH. Early
consultation with a medical toxicologist and nephrologist should be obtained for any patient with evidence of acidosis or signs of severe toxicity. (See 'Toxicity' above.)

● In the setting of acute overdose, clinicians should seek information about dose, coingestants (although such information is frequently unreliable), and whether other diabetic agents are used.
Patients may complain of nausea and abdominal pain; physical examination findings may include tachycardia, hypotension, and tachypnea in patients with severe lactic acidosis. Alterations in
mental status may be due to acidosis or hypoglycemia, although the latter is uncommon without concurrent use of a hypoglycemic agent. (See 'History and physical examination' above.)

● Routine laboratory evaluation of any acutely poisoned patient should include:

• Fingerstick glucose
Acetaminophen and salicylate levels
 • Electrocardiogram, to rule out conduction system poisoning by coingestants that affect the QRS or QTc intervals
• Pregnancy test in women of childbearing age (see "General approach to drug poisoning in adults")

● Specific laboratory testing in cases of known or suspected metformin toxicity should include:

• Arterial or venous blood gas for determination of acid-base status

• Basic chemistry to determine the bicarbonate and to assess renal function
• Serum lactate level to confirm the metabolic acidosis is in fact a lactic acidosis (see 'Laboratory evaluation' above)

● Victims of acute or chronic metformin toxicity rarely require tracheal intubation. Hyperpnea and tachypnea may reflect compensation for a metabolic acidosis and may not represent impending
respiratory failure. If intubation is required, the clinician should pay special attention to ventilator management. Minute ventilation sufficient to compensate for any underlying acidosis should be
maintained and arterial blood gas results checked frequently until the patient is stabilized. Persistent hypotension suggests profound toxicity. There is no antidote for metformin toxicity. (See
'Airway, breathing, circulation' above.)

● We suggest gastrointestinal (GI) decontamination with activated charcoal (AC) be performed in patients with acute metformin ingestion unless specific contraindications exist (Grade 2C). AC
should not be given to patients with toxicity from chronic use. The clinician must assess aspiration risk before any attempts to administer AC. (See 'Gastrointestinal decontamination' above.)

● Hypoglycemia should be treated with dextrose 0.5 to 1 g/kg IV, followed by a meal if food is not contraindicated. (See 'Hypoglycemia' above.)

● The use of sodium bicarbonate in metformin-induced lactic acidosis is controversial. We suggest administering sodium bicarbonate to patients with severe metabolic acidemia (arterial pH below
7.10 to 7.15) (Grade 2C). A reasonable goal is to maintain the pH above 7.15 until the acute toxicity resolves. (See 'Sodium bicarbonate' above and "Bicarbonate therapy in lactic acidosis".)

● Hemodialysis has been used successfully in patients with metformin-associated lactic acidosis due to chronic use or acute overdose. We recommend hemodialysis for patients with: lactate
concentrations >20 mmol/L; severe metabolic acidosis (pH ≤7.1); or who fail to improve within two to four hours despite appropriate supportive care and bicarbonate therapy (Grade 1C). We
suggest hemodialysis for patients with: lactate concentrations from 15 to 20 mmol/L, metabolic acidosis (pH 7 to 7.1), or comorbid conditions (shock, kidney impairment, liver failure, or
decreased level of consciousness) (Grade 2C). Early consultation with a medical toxicologist and a nephrologist should be obtained for any patient with metformin toxicity for which hemodialysis
may be required. (See 'Extracorporeal removal' above.)

● Patients reporting an acute ingestion should be observed for at least six to eight hours. Patients who are well appearing and who have a normal acid-base status after six to eight hours may be
discharged or transferred to the care of a psychiatrist. If a patient deteriorates during a period of observation, the clinician should promptly consult nephrology regarding the possibility of
hemodialysis. Serial acid-base determinations help document the patient's deterioration. (See 'Disposition' above.)

● Metformin is approved for the treatment of Type II diabetes in children. We treat children with metformin overdose in the same manner as adults. (See 'Pediatric considerations' above.)

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REFERENCES

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2. Bailey CJ, Day C. Traditional plant medicines as treatments for diabetes. Diabetes Care 1989; 12:553.

3. Harrigan RA, Nathan MS, Beattie P. Oral agents for the treatment of type 2 diabetes mellitus: pharmacology, toxicity, and treatment. Ann Emerg Med 2001; 38:68.
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5. Bailey CJ, Turner RC. Metformin. N Engl J Med 1996; 334:574.

6. Howlett HC, Bailey CJ. A risk-benefit assessment of metformin in type 2 diabetes mellitus. Drug Saf 1999; 20:489.

7. Graham GG, Punt J, Arora M, et al. Clinical pharmacokinetics of metformin. Clin Pharmacokinet 2011; 50:81.
8. Calello DP, Liu KD, Wiegand TJ, et al. Extracorporeal Treatment for Metformin Poisoning: Systematic Review and Recommendations From the Extracorporeal Treatments in Poisoning Workgroup.
Crit Care Med 2015; 43:1716.

9. Duong JK, Furlong TJ, Roberts DM, et al. The Role of Metformin in Metformin-Associated Lactic Acidosis (MALA): Case Series and Formulation of a Model of Pathogenesis. Drug Saf 2013; 36:733.
10. Bailey CJ, Wilcock C, Day C. Effect of metformin on glucose metabolism in the splanchnic bed. Br J Pharmacol 1992; 105:1009.

11. Vecchio S, Giampreti A, Petrolini VM, et al. Metformin accumulation: lactic acidosis and high plasmatic metformin levels in a retrospective case series of 66 patients on chronic therapy. Clin Toxicol
(Phila) 2014; 52:129.

12. Sirtori CR, Pasik C. Re-evaluation of a biguanide, metformin: mechanism of action and tolerability. Pharmacol Res 1994; 30:187.
13. Corchia A, Wynckel A, Journet J, et al. Metformin-related lactic acidosis with acute kidney injury: results of a French observational multicenter study. Clin Toxicol (Phila) 2020; 58:375.

14. Salpeter SR, Greyber E, Pasternak GA, Salpeter EE. Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus. Cochrane Database Syst Rev 2010; :CD002967.
15. Lalau JD, Race JM. Lactic acidosis in metformin-treated patients. Prognostic value of arterial lactate levels and plasma metformin concentrations. Drug Saf 1999; 20:377.

16. Seidowsky A, Nseir S, Houdret N, Fourrier F. Metformin-associated lactic acidosis: a prognostic and therapeutic study. Crit Care Med 2009; 37:2191.
17. Chang CT, Chen YC, Fang JT, Huang CC. Metformin-associated lactic acidosis: case reports and literature review. J Nephrol 2002; 15:398.

18. Gan SC, Barr J, Arieff AI, Pearl RG. Biguanide-associated lactic acidosis. Case report and review of the literature. Arch Intern Med 1992; 152:2333.
19. Khan IH, Catto GR, MacLeod AM. Severe lactic acidosis in patient receiving continuous ambulatory peritoneal dialysis. BMJ 1993; 307:1056.

20. Chang CT, Chen YC, Fang JT, Huang CC. High anion gap metabolic acidosis in suicide: don't forget metformin intoxication--two patients' experiences. Ren Fail 2002; 24:671.
21. Pearlman BL, Fenves AZ, Emmett M. Metformin-associated lactic acidosis. Am J Med 1996; 101:109.

22. Heaney D, Majid A, Junor B. Bicarbonate haemodialysis as a treatment of metformin overdose. Nephrol Dial Transplant 1997; 12:1046.
23. Lalau JD, Mourlhon C, Bergeret A, Lacroix C. Consequences of metformin intoxication. Diabetes Care 1998; 21:2036.

24. Dell'Aglio DM, Perino LJ, Kazzi Z, et al. Acute metformin overdose: examining serum pH, lactate level, and metformin concentrations in survivors versus nonsurvivors: a systematic review of the
literature. Ann Emerg Med 2009; 54:818.
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26. Lalau JD, Lacroix C, Compagnon P, et al. Role of metformin accumulation in metformin-associated lactic acidosis. Diabetes Care 1995; 18:779.
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27:285.
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35. https://www.liquidglassnanotech.com/poison-emergency-center-contact-numbers/ (Accessed on December 09, 2020).
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GRAPHICS

Metformin toxicity: Rapid overview

To obtain emergency consultation with a medical toxicologist, in the United States, call 1-800-222-1222, or the nearest international regional poison center. Contact information for regional poison centers around the world is available at the website referenced below. [1]

General information
Metformin is an antihyperglycemic agent whose major toxicity is lactic acidosis, which can occur with renal insufficiency, liver disease, and hemodynamic instability

Metformin may exacerbate hypoglycemia caused by other agents; taken alone it almost never causes hypoglycemia

Clinical features
Patients with metformin-induced lactic acidosis may complain of nausea and abdominal pain

Examination findings may include tachycardia, tachypnea, and hyperpnea

Diagnostic evaluation
For all poisoned patients, obtain: fingerstick glucose; ECG; acetaminophen and aspirin blood concentrations; serum pregnancy test in women of childbearing age

For suspected metformin toxicity, obtain: basic serum electrolytes, BUN and creatinine, serum bicarbonate, and serum lactate

Treatment
Secure airway, breathing, and circulation

For acute ingestions, give activated charcoal: 1 g/kg (generally 50 g in adults); Do not give activated charcoal to patients with chronic toxicity

For patients with profound acidosis (pH <7.10), consider sodium bicarbonate infusion (eg, give 1 to 2 meq/kg IV push; then put approximately 133 meq NaHCO3 in one liter D5W, run at 250 mL/hour in adults, or twice maintenance fluid infusion rate in children)

For patients with profound acidosis, highly elevated lactate, renal disease, or critical illness, obtain immediate nephrology consultation; hemodialysis will correct metformin-induced acid-base disturbance and slightly increase metformin clearance

Reference:

1. Poison emergency center contact numbers. Liquid Glass Nanotech. Available at: https://www.liquidglassnanotech.com/poison-emergency-center-contact-numbers/ (Accessed on May 25, 2021).

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Contributor Disclosures
Jason Chu, MD Nothing to disclose Andrew Stolbach, MD, MPH, FAACT, FACMT, FACEP Grant/Research/Clinical Trial Support: National Institute on Drug Abuse [Opioid-related illnesses]. Stephen J Traub, MD Nothing to
disclose Jonathan Grayzel, MD, FAAEM Nothing to disclose

Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be
provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence.

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