Metformin Overdosage
Metformin is a biguanide used to treat type 2 diabetes mellitus and most commonly prescribed oral hypoglycemic agent. Metformin is now also used to treat polycystic ovary syndrome and some malignancies. Despite a good safety profile in a majority of patients with diabetes, the risk of metformin-associated lactic acidosis is genuine when safety guidelines are ignored. Overdoses with metformin are rare, but may result in serious consequences. Case reports and small case series of serious toxicity from metformin overdosage can be found in the medical literature, often with the portrayal of extracorporeal methods for the management of the subsequent severe lactic acidosis. Lactic acidosis can defined as a metabolic acidosis with a blood pH less than 7.35 and a serum lactate more than 2 mmol per liter. It can occur either with therapeutic metformin dosing (which is rare) or in overdose situations. 0.03 cases of lactic acidosis per 1000 patient-years occur within therapeutic dosing, with a majority of these cases among patients that have contraindications to metformin (such as renal insufficiency). In overdose situations, lactic acidosis is seen much more habitually, even though the precise incidence is unclear. Lactic acidosis has been observed in 1.6% of metformin exposures reported to poison control centers; nevertheless, merely 10% of these exposures were due to deliberate overdoses. The incidence of metformin-associated lactic acidosis was 12.8% in a review of poison control center inquiries from Germany. The minimum reported lethal dose was found in a 42 year-old patient who had a blood metformin level of 188 µg/ml (e.g. therapeutic range level is usually between 0.5–2.5 µg/ml). Although the intake of 35 g of metformin has shown to be lethal, the maximum reported to Continue reading >>
Metformin Overdose
Tweet Save As with any medication, it is possible to overdose on metformin. Some of the effects of a metformin overdose may include low blood sugar or lactic acidosis. Symptoms of low blood sugar include blurred vision, shakiness, and extreme hunger. Some symptoms of lactic acidosis can include an irregular heartbeat, trouble breathing, and feeling tired. There are some treatment options for a metformin overdose, including dialysis or using a sugar solution to increase blood sugar levels. Metformin Overdose: An Overview Metformin (Glucophage®) is a prescription medication that has been licensed to treat type 2 diabetes. As with all medicines, it is possible to take too much metformin. Effects of a metformin overdose will vary depending on a number of factors, including how much metformin was taken and whether it was taken with any other medicines, alcohol, and/or drugs. If you happen to overdose on metformin, seek medical attention immediately. Symptoms of a Metformin Overdose The effects of a metformin overdose may include: Possible symptoms of low blood sugar include: Sweating Shakiness Extreme hunger Dizziness Cold sweats Blurry vision. More severe low blood sugar symptoms include: Changes in behavior, such as irritability Loss of coordination Difficulty speaking Confusion Loss of consciousness Coma Lactic acidosis symptoms include: Feeling tired or weak Muscle pain Trouble breathing Abdominal pain (or stomach pain) Feeling cold Dizziness or lightheadedness A slow or irregular heartbeat Loss of life. Tweet Our free DiscountRx savings card can help you and your family save money on your prescriptions. This card is accepted at all major chain pharmacies, nationwide. Enter your name and email address to receive your free savings card. Treatment for a Metformin Overdose Continue reading >>
Extracorporeal Treatment For Metformin Poisoning: Systematic Review And Recommendations From The Extracorporeal Treatments In Poisoning Workgroup
Background:Metformin toxicity, a challenging clinical entity, is associated with a mortality of 30%. The role of extracorporeal treatments such as hemodialysis is poorly defined at present. Here, the Extracorporeal Treatments In Poisoning workgroup, comprising international experts representing diverse professions, presents its systematic review and clinical recommendations for extracorporeal treatment in metformin poisoning. Methods:A systematic literature search was performed, data extracted, findings summarized, and structured voting statements developed. A two-round modified Delphi method was used to achieve consensus on voting statements and RAND/UCLA Appropriateness Method to quantify disagreement. Anonymized votes and opinions were compiled and discussed. A second vote determined the final recommendations. Results:One hundred seventy-five articles were identified, including 63 deaths: one observational study, 160 case reports or series, 11 studies of descriptive cohorts, and three pharmacokinetic studies in end-stage renal disease, yielding a very low quality of evidence for all recommendations. The workgroup concluded that metformin is moderately dialyzable (level of evidence C) and made the following recommendations: extracorporeal treatment is recommended in severe metformin poisoning (1D). Indications for extracorporeal treatment include lactate concentration greater than 20 mmol/L (1D), pH less than or equal to 7.0 (1D), shock (1D), failure of standard supportive measures (1D), and decreased level of consciousness (2D). Extracorporeal treatment should be continued until the lactate concentration is less than 3 mmol/L (1D) and pH greater than 7.35 (1D), at which time close monitoring is warranted to determine the need for additional courses of extracorporeal Continue reading >>
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6 Pearls About Metformin And Lactic Acidosis
Metformin accumulation: Lactic acidosis and high plasmatic metformin levels in a retrospective case series of 66 patients on chronic therapy. Vecchio S et al. Clin Toxicol 2014 Feb;52:129-135. Metformin is frequently used alone or in combination to treat type 2 diabetes. It lowers blood glucose by decreasing hepatic gluconeogenesis, predominantly by inhibiting mitochondrial respiratory chain complex I. The drug is eliminated mainly by the kidneys, and acute or chronic renal insufficiency may allow accumulation of the drug with increasing levels. A small percentage of patients on metformin develop severe lactic acidosis. There has been an ongoing controversy as whether this acidosis is metformin-associated or metformin-induced. This paper, from the Pavia Poison Control Centre in Northern Italy, helps shed light on this question. The authors retrospectively reviewed patients admitted to their toxicology unit over a 5-year period. Eligible patients were on chronic metformin therapy at the time of admission, had lactic acidosis (pH < 7.35, arterial lactate > 5 mmol/L), and elevated metformin levels (plasma metformin > 4 mcg/ml). Cases of acute overdose were excluded. The study objective was to correlate the metformin levels with measured pH, lactate levels, renal function, and mortality rate. Sixty-six eligible patients were identified. All patients presented with acute renal failure and severe lactic acidosis (mean pH 6.91, mean lactate 14.36 mmol/L). About half the patients had a pre-existing contraindication to metformin therapy, predominantly renal failure and/or heart disease. Approximately 75% presented after several days of a mild gastrointestinal prodrome with nausea, vomiting, and diarrhea; this may either have represented the initial manifestations of metformin po Continue reading >>
Toxicology Brief: Metformin Overdose In Dogs And Cats
Metformin is an antihyperglycemic prescription medication labeled for the treatment of noninsulin-dependent (type 2) diabetes mellitus in people. Metformin belongs to the biguanide group of oral antidiabetic agents and is the only biguanide currently available in the United States. Other biguanides, such as phenformin and buformin, were withdrawn from the U.S. market because of their higher risk of serious adverse effects (increased risk of lactic acidosis).1 Metformin has also been studied in cats as a potential treatment for diabetes mellitus.2,3 Most cases of metformin toxicosis reported to the ASPCA Animal Poison Control Center (APCC) involve dogs that have ingested their owners' medication. Metformin is available in single-ingredient preparations as well as in combination with other antidiabetic agents. Under the trade name Glucophage (Bristol-Myers Squibb) and in several generic formulations, metformin is available as tablets containing 500, 850, or 1,000 mg of metformin hydrochloride. Glucophage XR, the extended-release formulation, contains 500 or 750 mg of metformin hydrochloride. Two other metformin-only products available in the United States are Riomet (Ranbaxy Pharmaceuticals), a liquid oral formulation containing 500 mg/5 ml of metformin hydrochloride, and Fortamet (First Horizon Pharmaceutical) 500- or 1,000-mg extended-release tablets. MECHANISM OF ACTION AND PHARMACOKINETICS Biguanides are thought to lower postprandial glucose concentrations in diabetic patients by increasing glucose uptake and decreasing glucose production. Although the precise mechanisms by which metformin exerts its antihyperglycemic effects are not entirely certain, they are largely attributed to a reduction in hepatic gluconeogenesis, a decrease in intestinal glucose absorption, an Continue reading >>
The Toxicology Takedown #2 January 2015
The Toxicology Takedown #2 January 2015 A 15-Year-old female presents to the hospital 4 hours after ingestion of her diabetic fathers medication following a family dispute. Her family is unable to account for 75 x 5 mg glipizide and 29 x 500 mg metformin tablets. On arrival, she is vomiting and appears anxious and slightly sweaty with Glasgow Coma Score of 14/15. Her vital signs are pulse rate 90 bpm, blood pressure 110/75 mmHg, respiratory rate 18/min, and temperature of 36.8 C. A bedside blood glucose level is 54 mg/dl. Whats the immediate threat to life for this patient? Whats the mechanism of action of sulfonylurea medications, and how is it problematic in the management in toxicity? What are the antidotes for sulfonylurea toxicity? Whats concerning about metformin toxicity? What is the name of the syndrome that can develop in overdose and how it is managed? With respect to the ingestion of a potentially toxic amount of sulfonylureas, the immediate threat to life for this patient is hypoglycemia with potential progression to seizures and coma. This patient requires an IV line and administration of a bolus of 50 ml of 50% dextrose solution for correction of hypoglycemia and administration of another medication of minimize recurrent hypoglycemia. Glipizide is one of many sulfonylurea oral hypoglycemic agents. It exerts its effect by stimulating insulin release from the beta islet cells of the pancreas. All sulfonylureas inhibit ATP-sensitive K+ channels. This inhibition increases the membrane potential and depolarizes the cell. A subsequent influx of extracellular calcium ions through voltage-dependent calcium channels Occurs. An increase in the free intracellular calcium level is the signal, or second messenger, that triggers exocytosis and the release of insulin. F Continue reading >>
Metformin Litfl Life In The Fast Lane Medical Blog
Metformin rarely causes hypoglycaemia but it can cause a profound lactic acidosis in overdose and in patients with renal failure. Used therapeutically to inhibit glucogenogenesis and stimulate peripheral glucose uptake, in toxic doses it causes a profound lactaemia. All the mechanisms are unclear but it is in part due to the inhibition of gluconeogenesis (which lactate is required). Therefore in healthy individuals there is some build up of lactate, this is normally excreted in the urine but at impaired renal function or an acute overdose there is excess lactate. It is not metabolised and excretion relies solely on renal excretion A lactic acidosis in the context of therapeutic metformin has a high mortality rate and an underlying cause (sepsis) needs to be managed Metformin overdose is usually benign but doses > 10 grams are concerning Lactic acidosis will occur in these individuals who are susceptible (renal, cardiac, respiratory failure) or in patients who have ingested co-ingestants or are on medications that impair cardiac and renal function Severe lactic acidosis usually manifests with non-specific symptoms several hours later but can progress to coma, shock and death Children: Unintentional ingestion of up to 1700mg is benign. Hypoglycaemia, if present can be managed with dextrose . Severe acidosis and hyperkalaemia may require the administration of sodium bicarbonate (1 2 mmol/kg). However, it is likely the patient is already hyperventilating to compensate for the metabolic acidosis, haemodialysis is the ultimate priority. If in a patient on therapeutic metformin, stop further administration and seek the underlying cause for their deterioration (sepsis, acute kidney injury) Screening: 12 lead ECG, BSL, Paracetamol level 50 grams of charcoal to the co-operative Continue reading >>
Toxicology Case Of The Month: Oral Hypoglycaemic Overdose
Toxicology case of the month: oral hypoglycaemic overdose J Soderstrom, L Murray, M Little, Sir Charles Gairdner Hospital, Perth, WA, Australia L Murray, F F S Daly, M Little, University of Western Australia, Perth, WA, Australia L Murray, F F S Daly, M Little, New South Wales Poison Information Centre, New Children's Hospital, Westmead, NSW, Australia F F S Daly, Royal Perth Hospital, Perth, WA, Australia Copyright 2006 Emergency Medicine Journal. This article has been cited by other articles in PMC. A teenager ingests 375 mg of glipizide and 14.5 g of melformin intentionally in a small country town. She presents to the local medical facility with symptoms and signs of hypoglycaemia. Using a risk assessment based approach, the management of suiphonylurea and metformin overdose is discussed. Sulphonylurea overdose invariably results in profound hypoglycaemia that requires resuscitation with IV dextrose and the use of octreotide as an antidote. Metfonnin overdose rarely causes problems. Keywords: glipizide, hypoglycaemia, lactic acidosis, metformin, overdose This is the first in a series of cases presented by the Western Australian Toxicology Service. The cases are selected for their relevance to emergency medicine practice and emphasise the importance of risk assessment in formulating a coherent management plan for the acutely poisoned patient (boxes 1 and 2). These principles were discussed in depth in the introductory article for this series. 1 A 15 year old female presents to the hospital of a small remote town 2600 km north east of Perth. Some 4 h ago, following a family dispute, she ingested all of her diabetic father's medications. Her family are unable to account for 755 mg glipizide and 29500 mg metformin tablets. On arrival, she is vomiting and appears anxious Continue reading >>
A Pediatric Suicide Attempt By Ingestion Of Metformin, Glimepiride And Sulpiride: A Case Report And Literature Review
1Medical Biological Laboratory Service, Regional Hospital of Kasserine, 1200 Kasserine, Tunisia 2Toxicology Laboratory Service, hospital Farhat Hached of Sousse, 4000 Sousse, Tunisia 3Internal Medicine Service, Regional Hospital of Kasserine, 1200 Kasserine, Tunisia *Corresponding Author: Gharsalli Tarek Medical Biological Laboratory Service Regional Hospital of Kasserine, 1200 Kasserine, Tunisia Tel: +21697070320 Fax: +21677473777 E-mail: [email protected] Citation: Tarek G, Kais G, Ramzi G (2016) A Pediatric Suicide Attempt by Ingestion of Metformin, Glimepiride and Sulpiride: A Case Report and Literature Review. J Clin Toxicol 6:310. doi:10.4172/2161-0495.1000310 Copyright: © 2016 Tarek G, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Visit for more related articles at Journal of Clinical Toxicology Abstract A case of a pediatric patient poisoning after ingestion of metformin, glimepiride and sulpiride, he was presented to the emergency service with symptoms and signs of hypoglycemia. Using a risk assessment based approach, the management of glimepiride and metformin overdose is discussed. Glimepiride overdose invariably results in profound hypoglycemia that requires resuscitation with IV dextrose and the use of octreotide as an antidote. Metformin overdose rarely causes problems. The acute sulpiride poisoning is poorly reported in the medical literature. Keywords Pediatric; Suicide attempt; Poisoning; Metformin; Glimepiride; Sulpiride Introduction Children suffering from physical, mental or psychological problems are being increasingly evaluated and treated in ped Continue reading >>
Metformin Overview
Metformin is a prescription medication used to treat type 2 diabetes. Metformin belongs to a group of drugs called biguanides, which work by helping your body respond better to the insulin it makes naturally, decreasing the amount of sugar your liver makes, and decreasing the amount of sugar your intestines absorb. This medication comes in tablet, extended-release tablet, and liquid forms. It is taken up to 3 times daily, depending on which form you are taking. Swallow extended-release tablets whole. Common side effects of metformin include diarrhea, nausea, and upset stomach. Metformin is a prescription medication used to treat type 2 diabetes. This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information. Metformin may be found in some form under the following brand names: Serious side effects have been reported including: Lactic Acidosis. In rare cases, metformin can cause a serious side effect called lactic acidosis. This is caused by a buildup of lactic acid in your blood. This build-up can cause serious damage. Lactic acidosis caused by metformin is rare and has occurred mostly in people whose kidneys were not working normally. Lactic acidosis has been reported in about one in 33,000 patients taking metformin over the course of a year. Although rare, if lactic acidosis does occur, it can be fatal in up to half the people who develop it. It is also important for your liver to be working normally when you take metformin. Your liver helps remove lactic acid from your blood. Make sure you tell your doctor before you use metformin if you have kidney or liver problems. You should also stop using metformin and call your doctor right away if you have signs of lactic acidosis. Lactic acidosis is a medical emergency that must be treate Continue reading >>
Metformin
Metformin, marketed under the trade name Glucophage among others, is the first-line medication for the treatment of type 2 diabetes,[4][5] particularly in people who are overweight.[6] It is also used in the treatment of polycystic ovary syndrome.[4] Limited evidence suggests metformin may prevent the cardiovascular disease and cancer complications of diabetes.[7][8] It is not associated with weight gain.[8] It is taken by mouth.[4] Metformin is generally well tolerated.[9] Common side effects include diarrhea, nausea and abdominal pain.[4] It has a low risk of causing low blood sugar.[4] High blood lactic acid level is a concern if the medication is prescribed inappropriately and in overly large doses.[10] It should not be used in those with significant liver disease or kidney problems.[4] While no clear harm comes from use during pregnancy, insulin is generally preferred for gestational diabetes.[4][11] Metformin is in the biguanide class.[4] It works by decreasing glucose production by the liver and increasing the insulin sensitivity of body tissues.[4] Metformin was discovered in 1922.[12] French physician Jean Sterne began study in humans in the 1950s.[12] It was introduced as a medication in France in 1957 and the United States in 1995.[4][13] It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system.[14] Metformin is believed to be the most widely used medication for diabetes which is taken by mouth.[12] It is available as a generic medication.[4] The wholesale price in the developed world is between 0.21 and 5.55 USD per month as of 2014.[15] In the United States, it costs 5 to 25 USD per month.[4] Medical uses[edit] Metformin is primarily used for type 2 diabetes, but is increasingly be Continue reading >>
Metformin Overdose Symptoms And Treatment: What You Should Know
What is Metformin? It is a type of medication called a biguanide, which is used to treat people with type 2 diabetes. Type 2 diabetes is a chronic condition where the body cannot make enough insulin or use it properly. Most people with type 2 diabetes can control their blood sugar levels through regular exercise and healthy diet. In case this does not work, metformin is the first oral diabetes medication that is prescribed to people with type 2 diabetes. It can also be used together with insulin or other diabetes medication to reduce blood glucose levels when it is too high. Controlling high blood sugar is important because it prevents the risk of health complications such as loss of limbs, kidney damage and nerve problems. However, this medicine should not be used to treat type 1 diabetes, a condition where the body produces little or no insulin. This is because metformin works by helping the body respond better to the insulin it already makes. The drug works by reducing the amount of glucose that is produced by your liver and by decreasing insulin that is absorbed by the intestines. This helps to control blood glucose levels in people with type 2 diabetes. Dosage The dosage of metformin depends on your medical condition, response to treatment and kidney function. Do not change your dosage without your doctor’s permission. Your doctor may ask you to start at a lower dose, then gradually increase the dosage to reduce the risk of side effects like stomach upset. This medication is supposed to be taken by mouth, usually 1 to 3 times every day with meals. You should drink plenty of fluids as you take this medication unless directed otherwise by your healthcare provider. Metformin overdose symptoms and treatment Although not common, a metformin overdose can result in seri Continue reading >>
Metformin Poisoning: A Complex Presentation
Metformin poisoning: A complex presentation We are experimenting with display styles that make it easier to read articles in PMC. The ePub format uses eBook readers, which have several "ease of reading" features already built in. The ePub format is best viewed in the iBooks reader. You may notice problems with the display of certain parts of an article in other eReaders. Generating an ePub file may take a long time, please be patient. Metformin poisoning: A complex presentation Manish Jagia, Salah Taqi, and Mahmud Hanafi The objective of this case report is to highlight presentation, complications and treatment of metformin poisoning. Patient after ingestion of 45gms of metformin developed colicky abdominal pain, severe tachypnea and vomiting. He developed severe lactic acidosis, cardiac arrest, pancreatitis and hemolytic anemia which was treated with charcoal, sodium bicarbonate, early initiation of high volume continuous veno-venous hemofiltration and supportive therapy. Metformin poisoning is a rare presentation and we discuss course of events in the management of metformin poisoning and its associated complications. Keywords: Cardiac arrest, haemolytic anemia, lactic acidosis, metformin poisoning, pancreatitis Metformin is a biguanide oral hypoglycemic agent used for non-insulin dependent diabetes mellitus (NIDDM). Metformin poisoning can cause fatal complications like severe lactic acidosis, haemolytic anemia and pancreatitis. Early diagnosis can result in successful outcome. Here, we report a case having good recovery despite metformin induced complications and cardiac arrest. A 36-year-old man presented in the Emergency Department after ingestion of 45 g metformin. He presented with colicky abdominal pain, severe tachypnoea and vomiting. He had history of NIDDM Continue reading >>
Overdose Of Oral Antidiabetic Medications And Insulin
Overdose of Oral Antidiabetic Medications and Insulin Authors: Diana Strasburger, MD, RDMS, Attending Physician, Department of Emergency Medicine, Advocate Christ Medical Center, Oak Lawn, IL. Janna H. Villano, MD, Resident Physician, Department of Emergency Medicine, Advocate Christ Medical Center, Oak Lawn, IL. Peer Reviewer: Gina Piazza, DO, Associate Professor of Emergency Medicine, Georgia Health Sciences University, Augusta, GA. — Sandra M. Schneider, MD, Editor Treating the hypoglycemia and metabolic derangements caused by antidiabetic medications, especially in massive overdose, are dynamic as new agents are introduced. Emergency physicians should know potential pitfalls in order to effectively and safely manage these patients, avoiding rebound hypoglycemia and premature discharge without appropriate monitoring. This article will review the clinical presentation and management of toxicity from commercially available antidiabetic agents in the United States, including oral hypoglycemic agents such as sulfonylureas and oral antihyperglycemic agents such as biguanides, as well as novel antidiabetic agents and insulin. Introduction Diabetes mellitus (DM) is an ever-increasing epidemic facing the current health care system. Its prevalence is increasing worldwide from an estimated 30 million in 1985 to 150 million in 2000, 171 million in 2007, and an anticipated 366 million in 2030.1,2 Medications used to treat diabetes are diverse, and often patients use multiple classes of medications to obtain euglycemia. Oral preparations can be divided into two categories based on their pharmacodynamics and effect or lack of an effect on insulin: hypoglycemic agents such as sulfonylureas and meglitinides; and antihyperglycemic agents such as biguanides, alpha-glucosidase inhibi Continue reading >>
Ph 6.68surviving Severe Metformin Intoxication
Metformin, a widely used anti-diabetic agent of the biguanide family, although generally safe, 1 , 2 , 3 , 4 holds the risk of developing a potentially lethal acidosis. 5 , 6 The association between lactic acidosis and metformin is well-established but rarely seen in patients taking this medication. 7 Its elimination relies solely on kidneys excretion, 8 so its accumulation is feasible in just two circumstances: renal failure (RF) and acute overdosage. At normal dosage, a toxic accumulation of drug requires time after the development of RF, due to metformin high clearance. About 90% of the drug is eliminated by glomerular filtration and tubular secretion (serum half-life of 1.55 h). Moreover, RF is itself associated with acidosis as it impairs kidneys ability to excrete protons. Acute intoxication on the other hand is a viable option in those cases where renal function is normal and can correlate with a psychiatric disorder. The mechanism thought to be responsible for lactic acidosis is suppression of gluconeogenesis forming lactate, pyruvate, glycerol and amino acids leading to lactate accumulation, 9 a risk that is increased by either chronic or acute RF (ARF). Usually hyperlactatemia is the most common finding leaving lactic acidosis for the most severe intoxications. A 47-year-old, apparently previously fit, non-insulin-dependent diabetic male was brought to the Emergency Department for hypoglycemia, agitation and hyperventilation. Ambulance crew found blood glucose level at 1.33 mmol/l (24 mg/dl) and administered 20 ml of 33% glucose solution followed by other 250 ml at 5%. At the arrival in the Emergency Room, the patient was confused and agitated with no signs of respiratory distress or shock. Arterial blood gases (ABG) and laboratory tests are summarized in Tab Continue reading >>
