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
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 - National Library Of Medicine Hsdb Database
For more information, search the NLM HSDB database. IDENTIFICATION AND USE: Metformin is antihyperglycemic, not hypoglycemic agent. It does not cause insulin release from the pancreas and does not cause hypoglycemia, even in large doses. HUMAN EXPOSURE AND TOXICITY: Metformin is believed to work by inhibiting hepatic glucose production and increasing the sensitivity of peripheral tissue to insulin. It does not stimulate insulin secretion, which explains the absence of hypoglycemia. Metformin also has beneficial effects on the plasma lipid concentrations and promotes weight loss. Accumulation of metformin may occur in patients with renal impairment, and such accumulation rarely can result in lactic acidosis, a serious, potentially fatal metabolic disease. Lactic acidosis constitutes a medical emergency requiring immediate hospitalization and treatment; lactic acidosis is characterized by elevated blood lactate concentrations, decreased blood pH, electrolyte disturbances with an increased anion gap, and an increased lactate/pyruvate ratio. Lactic acidosis also may occur in association with a variety of pathophysiologic conditions, including diabetes mellitus, and whenever substantial tissue hypoperfusion and hypoxemia exist. Approximately 50% of cases of metformin-associated lactic acidosis have been reported to be fatal. No evidence of mutagenicity or chromosomal damage was observed in in vitro test systems, including human lymphocytes assay. ANIMAL STUDIES: No evidence of carcinogenic potential was seen in a 104-week study in male and female rats receiving metformin hydrochloride dosages up to and including 900 mg/kg daily or in a 91-week study in male and female mice receiving metformin hydrochloride at dosages up to and including 1500 mg/kg daily. Cancer preventive e Continue reading >>
A Comparison Between The Effects Of Metformin And N -acetyl Cysteine (nac) On Some Metabolic And Endocrine Characteristics Of Women With Polycystic Ovary Syndrome
Full Terms & Conditions of access and use can be found at Download by: [Kashanian Maryam] Date: 25 December 2015, At: 00:26 ISSN: 0951-3590 (Print) 1473-0766 (Online) Journal homepage: A comparison between the effects of metformin and N-acetyl cysteine (NAC) on some metabolic and endocrine characteristics of women with Forough Javanmanesh, Maryam Kashanian, Maryam Rahimi & Narges To cite this article: Forough Javanmanesh, Maryam Kashanian, Maryam Rahimi & Narges Sheikhansari (2015): A comparison between the effects of metformin and N-acetyl cysteine (NAC) on some metabolic and endocrine characteristics of women with polycystic ovary syndrome, Gynecological Endocrinology, DOI: 10.3109/09513590.2015.1115974 To link to this article: Department of Obstetrics & Gynecology, Firoozgar Teaching Hospital, Iran University of Medical Sciences, Tehran, Iran, & Gynecology, Akbarabadi Teaching Hospital, Iran University of Medical Sciences, Tehran, Iran, and Medicine, University of Southampton, Southampton, UK Objective: To compare N-acetyl cysteine (NAC) and metformin on polycystic ovary syndrome Method: Study was performed as a randomized double-blind clinical trial on women with diagnosis of PCOS without additional complications. In one group, oral NAC 600 mg, three times a day and in the other group, 500 mg oral metformin, three times a day were prescribed. Duration of treatment was 24 weeks, and after finishing this period of treatment, fasting blood glucose (FBS) and insulin, lipid profile and Homeostasis Model Assessment (HOMA) index were measured (all the blood samples were taken while fasting) and were compared in the two Results: Forty-six women in NAC group and 48 women in metformin group finished the study. The two groups did not show significant difference according to a Continue reading >>
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 >>
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 >>
A Pediatric Suicide Attempt By Ingestion Of Metformin, Glimepiride Andsulpiride: A Case Report And Literature Review
Received date: March 01, 2016; Accepted date: July 04, 2016; Published date: July 11, 2016 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. 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. Pediatric; Suicide attempt; Poisoning; Metformin; Glimepiride; Sulpiride Children suffering from physical, mental or psychological problems are being increasingly evaluated and treated in pediatric clinical [ 1 ]. Pediatric emergency departments frequently admit that a lot of children have attempted to commit suicide. Cases vary depending on both the child's age and some risk factors [ 2 ]. The main profile is a female between 12 and 14 years of age that attempted suicide at home using medication especially benzodiazepines. Among those under 10 years, there is a significant predominance of males using non pharmacological methods [ 3 ]. Understanding how childr Continue reading >>
Fatal Metformin Overdose Presenting With Progressive Hyperglycemia
Go to: CASE REPORT A 29-year-old man ingested metformin in a suicide attempt. The patient consumed the entire remaining contents of his father’s prescription metformin bottle that originally contained 100 tablets of 850 mg each. The father stated that the bottle had contained at least three-quarters of its original contents, putting the ingested dose between 64 and 85 grams. The patient also consumed ethanol, but denied any other co-ingestants. The parents discovered the overdose around 6:30 a.m., about 5 ½ hours post-ingestion, when the patient began complaining of vomiting, diarrhea, thirst, abdominal pain and bilateral leg pain. Paramedics were called, who found the patient to be agitated with a fingerstick glucose level of 180 mg/dL. The patient had a history of psychosis and depression, including prior suicide attempts by drug ingestion. He was not taking any prescribed medications, having discontinued olanzapine and sertraline several months earlier. The patient had no personal history of diabetes, despite the family history of type II diabetes in his father, who was taking no other anti-diabetic medications than metformin. The patient admitted to daily ethanol and tobacco use, but denied any current or past use of illicit drugs. He had no surgical history or known allergies. Vital signs on arrival to the Emergency Department (ED) were temperature of 35.2°C (rectal), pulse of 113 beats/min, blood pressure of 129/59 mmHg, respirations at 28 breaths/min with 100% saturation via pulse oximetry on room air. The patient was awake and oriented x4, but agitated and slightly confused (GCS=14). Pupils were equal and reactive at 4mm and the oral mucous membranes were dry. Other than tachycardia, the heart and lung exams were unremarkable. The abdomen was mildly tender t Continue reading >>
1322: Prolonged Hemodialysis-an Antidote For Metformin Induced Lactic Acidosis
Introduction: A 60 year old Hispanic man with Type 2 diabetes mellitus and on Metformin was brought to the Emergency Department with vomiting and diarrhea of two days duration. On physical examination, he was noted to be hypothermic, hypotensive and confused. Laboratory work-up revealed severe life threatening high anion gap metabolic acidosis,hyperlactatemia and markedly elevated creatinine of 9 mg/dl (normal 0.6-1.2 mg/dl) without prior laboratory data. Patient was intubated, vasopressor and sodium bicarbonate intravenous drips initiated and arrangement made for urgent hemodialysis based on a high index of suspicion for metformin poisoning. After 4 hours of hemodialysis, there was marked improvement in the laboratory parameters post hemodialysis. He was given another session of hemodialysis with the same hemodialysis prescription next day for 6 hours with further improvement. Initial metformin levels were found to be 46 mg/l (therapeutic levels < 2 mg/l),later confirming the diagnosis. On the 3rd day, renal function started to improve with further reduction of serum metformin level to 1.5 mg/l. He was extubated on day 5 and subsequently discharged after making a complete recovery.Lactic acidosis is a rare and potentially lethal complication of metformin therapy. It is seen in 6.3 cases per 100,000 patients on treatment(1). It can be a consequence of acute overdose or secondary to impaired metformin renal clearance. Most of the patients with metformin induced lactic acidosis have other co-morbidities like cardiopulmonary or severe renal or liver disease. Volume depletion, use of drugs that interfere with renal autoregulation like angiotensin converting enzyme Inhibitors and nonsteroidal anti-inflammatory drugs can be contributory factors. The mechanism of action is th 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 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 >>
Tennessee Poison Center - 03-23-17 How Does Metformin Differ From Other Oral Hypoglycemic Drugs? - Vanderbilt Health Nashville, Tn
03-23-17 How does Metformin differ from other oral hypoglycemic drugs? 03-23-17 How does Metformin differ from other oral hypoglycemic drugs? How does Metformin differ from other oral hypoglycemic drugs? Metformin is a biguanide agent and the drug-of-choice for the treatment of newly diagnosed type-2 diabetes mellitus, making it one of the most widely prescribed medications in the world. With over half a century of clinical experience, metformin is generally recognized as safe with the most frequent adverse effects being gastrointestinal (i.e. nausea, indigestion, abdominal cramps/bloating, diarrhea). Metformin acts to reduce hepatic glucose production, reduce intestinal glucose absorption, and increase skeletal muscle glucose uptake and utilization. Because it does not affect the release of insulin or other pancreatic hormones, metformin is rarely associated with hypoglycemia. Metformin impairs mitochondrial respiration and inhibits the conversion of lactate to pyruvate. This results in both an increased production and decreased elimination of lactate with a subsequent acidosis known as metformin-associated lactic acidosis (MALA). MALA is a serious but rare complication of metformin therapy (less than 10 events per 100,000 patient-years of exposure) with a mortality rate that approaches 50%. MALA as a result of therapeutic use is typically due to an acute event that affects the patients ability to excrete metformin (i.e. acute kidney injury) coupled with risk factors that increase lactate production and/or retention (see table below). Small changes in hydration, renal function, plasma metformin concentrations, and tissue oxygenation often lead into a positive feedback loop that worsens the lactic acidosis. Acute metformin overdose is the most frequent cause of MALA. S Continue reading >>
Toxicology Of Oral Antidiabetic Medications
Toxicology of Oral Antidiabetic Medications Am J Health Syst Pharm.2006;63(10):929-938. In 1996, the Food and Drug Administration approved the labeling for metformin (dimethylbiguanide), the only biguanide currently available in the United States. Phenformin, the other previously available biguanide, was withdrawn from the market in 1977 because of an association with lactic acidosis. Buformin, another biguanide, is not available in the United States. The complex of mechanisms of action of metformin is multifaceted but appears to include delayed glucose absorption, increased intestinal glucose utilization, increased intestinal lactate production, inhibition of hepatic gluconeogenesis, decreased lipid oxidation, decreased free fatty acid concentration, and increased peripheral insulin-related glucose uptake.[ 70 ] Metformin absorption is incomplete, with 20-30% found in the feces. Oral bioavailability is 40-60%, depending on the dose ingested, with greater doses producing lower bioavailability.[ 71 ] The reduced bioavailability may result from the drug binding by the intestinal wall.[ 72 ] The rate of absorption is slower than the rate of elimination, which makes absorption a rate-limiting step in the elimination half-life.[ 73 , 74 ] Absorption, in therapeutic doses, is expected to be complete in 6 hours. In an overdose situation involving massive doses, absorption may be prolonged. About 90% of the absorbed metformin is eliminated through the kidneys within the first 24 hours in patients with normal renal function.[ 72 ] Metformin has no metabolites. Metformin is the second most commonly prescribed oral antidiabetic medication in both monotherapy and combination therapy.[ 11 ] In 2004, metformin had the highest number of reports to U.S. poison control centers and the Continue reading >>
Oral Hypoglycemic Agent Toxicitytreatment & Management
Oral Hypoglycemic Agent ToxicityTreatment & Management Author: David Tran, MD; Chief Editor: Timothy E Corden, MD more... The main goal in oral hypoglycemic agent exposure is supportive care, which includes airway, breathing, and circulation. Intravenous administration of glucose rapidly resolves the effects of hypoglycemia. Its onset is quicker than oral administration of sugar, and it is safer in patients with a depressed mental status who should not take anything by mouth for fear of aspiration. Glucagon is helpful and can be administered intravenously, intramuscularly, or subcutaneously. Glucagon is particularly useful in the intramuscular mode when intravenous access cannot be obtained immediately. Generally, all symptomatic patients who present with hypoglycemia need admission to the hospital in a monitored setting. Patients who remain asymptomatic and who do not develop hypoglycemia in the first 8-12 hours may be discharged safely home. However, the data from one study suggest that because accidental ingestion of sulfonylurea results in delayed and often prolonged hypoglycemia, admission for at least 16 hours is recommended, with frequent glucose monitoring. [ 17 ] At minimum, patients need intravenous access. If the patient is lethargic, then oxygen, continuous cardiac monitoring, and pulse oximeter are indicated. Until the patient totally regains normal mental status, do not administer anything by mouth. Administer intravenous glucose to all patients with hypoglycemic symptoms. Depending on the amount of the drug and its half-life, patients may require intravenous glucose administration for anywhere from several hours to several days. If patients do not respond to continuous glucose administration with supplemental boluses, then octreotide or diazoxide can be Continue reading >>
Metformin-related Acidosis In A Woman While Performing Haj: A Conservative Approach Ansari Rs, Mady Af, Qutub Ho, Althomaly E, Alzayer Za, Moulana Aa - Saudi J Kidney Dis Transpl
Metformin is a biguanide that enhances the release of glucose from the liver and the insulin effect on peripheral tissues thus decreasing the blood glucose. The most serious sideeffect of metformin is lactic acidosis due to inhibition of hepatic gluconeogenesis and/or reduction of conversion of lactic acid, pyruvic acid or alanine to glucose. The yearly incidence of lactic acidosis in previous reports was less than five episodes in every 100,000 treated individuals. Still, there is no particular antidote for metformin-induced lactic acidosis and its treatment mainly involves the correction of acidemia. [1] Considerable efficacy has been observed in the use of hemodialysis to treat the metformin-induced lactic acidosis. Hemodialysis application is currently recommended in patients with severe metabolic acidosis (pH < 7.1) and renal failure. It has been shown that plasma metformin concentrations are only slightly increased when the estimated glomerular filtration rate is 30 mL/ min/1.73 m2. [2] We present a case of successful management of metformin-associated metabolic acidosis, treated simply with intravenous sodium bicarbonate and aggressive hydration and intensive monitoring. Our aim in presenting this article is to demonstrate that even normal doses of metformin can induce severe acidosis. A 55-year-old woman with type 2 diabetes mellitus presented to the emergency department (ED) with altered level of consciousness. The patient was on metformin 500 mg three times a day. Her respiratory rate was 30 breaths/min, non-invasive blood pressure was 90/50 mm Hg, heart rate was 90 beats/min and temperature was 37C. The physical exam was otherwise unremarkable. The laboratory investigations [Table 1] on admission revealed plasma creatinine: 12.72 mg/dL, blood urea nitrogen: Continue reading >>
