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Metformin Is Poison

Mala: Metformin-associated Lactic Acidosis

Mala: Metformin-associated Lactic Acidosis

By Charles W. O’Connell, MD Introduction Metformin is a first-line agent for type 2 diabetes mellitus often used as monotherapy or in combination with oral diabetic medications. It is a member of the biguanide class and its main intended effect is expressed by the inhibition of hepatic gluconeogenesis. In addition, metformin increases insulin sensitivity, enhances peripheral glucose utilization and decreases glucose uptake in the gastrointestinal tract. Phenformin, a previously used biguanide, as withdrawn from the market in the 1970’s due its association with numerous cases of lactic acidosis. Metformin is currently used extensively in the management of diabetes and is the most commonly prescribed biguanide worldwide. The therapeutic dosage of metformin ranges from 850 mg to a maximum of 3000 mg daily and is typically divided into twice daily dosing. It is primarily used in the treatment of diabetes but has been used in other conditions associated with insulin resistance such as polycystic ovarian syndrome. MALA is a rare but well reported event that occurs with both therapeutic use and overdose states. Case presentation A 22-year-old female presents to the Emergency Department after being found alongside a suicide note by her family. She was thought to have taken an unknown, but large amount of her husband’s metformin. She arrives at the ED nearly 10 hours after ingestion. She was agitated, but conversant. She reports having nausea and vague feelings of being unwell and is very distraught over the state of her critically ill husband. She has some self-inflicted superficial lacerations over her left anterior forearm. Her vital assigns upon arrival were: T 98.9 degrees Fahrenheit, HR initially 140 bpm which improved to 110 bpm soon after arrival, BP 100/50, RR 22, Continue reading >>

Oral Hypoglycemic Agent Toxicity

Oral Hypoglycemic Agent Toxicity

Author: David Tran, MD; Chief Editor: Timothy E Corden, MD more... Oral hypoglycemic agentssulfonylureaswhich are used to treat patients with type 2 diabetes, [ 1 ] are among the most widely prescribed medications in the world. Wide availability of these medications increases the potential for either intentional or unintentional overdose in pediatric and adult populations. [ 2 ] First-generation sulfonylurea compounds became widely available in 1955. They are acetohexamide, chlorpropamide, tolazamide, and tolbutamide. First-generation agents have long half-lives (eg, 49 hours for chlorpropamide). Second-generation sulfonylureas were introduced in 1984 and include glipizide, glyburide, and glimepiride. Second-generation sulfonylureas are more potent and have shorter half-lives than the first-generation sulfonylureas. Other agents besides sulfonylureas are used to treat type 2 diabetes, including biguanides, alpha-glucosidase inhibitors, and thiazolidinediones. Metformin (Glucophage in the United States), a biguanide, is one such agent. [ 3 ] Even in overdose, these agents do not decrease serum glucose below euglycemia; consequently, they are appropriately referred to as antihyperglycemic agents rather than hypoglycemic agents. Although overdose of antihyperglycemic agents can have dangerous adverse effects (for example, lactic acidosis from metformin [ 4 ] ), this article focuses on acute overdose of sulfonylureas. Hypoglycemia from sulfonylureas can result from small doses, can be delayed in onset, and can be persistent. Prolonged observation and intensive care to restore and maintain euglycemia may be required. [ 5 ] (See Treatment and Medication.) Sulfonylureas are sulfonamide derivatives but do not have any antibacterial activity. The exact mechanism of sulfonylurea Continue reading >>

Hyperglycemia After Metformin Overdose: A Case Report Sabiha Sahina, D, Cigdem Binayb, Enver Simsekb, Ener Cagri Dinleyicia,

Hyperglycemia After Metformin Overdose: A Case Report Sabiha Sahina, D, Cigdem Binayb, Enver Simsekb, Ener Cagri Dinleyicia,

Articles © The authors | Journal compilation © Int J Clin Pediatr and Elmer Press Inc™ | www.theijcp.org This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited 44 Case Report Int J Clin Pediatr. 2016;5(3-4):44-46 ressElmer Kursat Bora Carmanc Abstract We present a case of a 16-year-old non-diabetic girl who ingested over 35 tablets (glucophage Merck 850 mg) of metformin in a sui- cide attempt. She presented to pediatric emergency department with severe lactic acidosis and a progressively increasing serum glucose level. She was in a coma state at the time of admission, Glasgow coma scale was 3/15 and arterial blood pressure was 106/45 mm Hg. Arterial blood gas (ABG) analysis indicated severe metabolic acido- sis (pH 6.7) with high anion gap -30.5, PCO2 13.2, HCO3 3.9, BE -30, lactate 14.54 mmol/L, blood glucose 497, amylase 531 IU/L, and uric acid 10.47 mg/dL. Serum ethanol, acetaminophen and salicylates were measured and found to be undetectable. Electrocardiographic monitoring demonstrated a narrow-complex sinus tachycardia. She was intubated, totally 2,000 cc/m2 fluid and NaHCO3 were given, and insulin infusion 0.1 units/kg was started for blood glucose of 497 mg/dL. But the patient suffered several cardiac arrests with pulse- less electrical activity and ultimately expired 25 h after the ingestion. The patient was transferred to pediatric intensive care unit (PICU) for high-volume continuous veno-venous hemofiltration (CVVH). Despite the supportive care in ICU, she died due to multiple organ failures after 48 h of hospitalization. Keywords: Continue reading >>

Toxicology Brief: Metformin Overdose In Dogs And Cats

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 >>

Hemodialysis In Metformin Poisoning

Hemodialysis In Metformin Poisoning

Extracorporeal Treatment fo Metformin Poisoning: Systematic Review and Recommendations From the Extracorporeal Treatments in Poisoning Workshop. Calello DP et al.Crit Care Med 2015 Apr 9 [Epub ahead of print] Metformin is now the oral drug most commonly prescribed to treat non-insulin-dependent diabetes in the United States. The drug is large eliminated by the kidneys. Toxicity presents with severe lactic acidosis, and can occur when decreasing renal function causes accumulation of therapeutic doses, or in the case of acute deliberate overdose. According to some reports metformin poisoning, though rare, is associated with a mortality rate of 30%. Metformin is a small molecule that is not protein-bound, making it amenable to dialysis despite having an appreciable volume of distribution (1-5 L/kg.) This paper, from the Extracorporeal Treatments in Poisoning (ExTRIP) Workgroup , aimed to review systematically literature relevant to the use of extracorporeal methods to treat metformin poisoning, and present recommendations for using such methods. The authors identified 175 relevant articles, including case reports and observation studies. Unfortunately, as in this groups previous papers regarding different poisons, the quality of the evidence was so poor that all of their recommendations were rated 1D (1=strong recommendation, D=very low level of evidence). As weve pointed out in discussing the groups earlier papers, this makes their conclusions opinions rather than evidence-based recommendations. However, given the expertise and experience of members of the group, their opinions must be reckoned with. The paper concludes that metformin is dialyzable and that extracorporeal treatment (ECTR) is recommended in severe metformin poisoning. Specific suggested indications are as Continue reading >>

Diabetes Medication

Diabetes Medication

The Full Story Pills to treat diabetes are among the most dangerous medicines small children get into. A child who swallows even one of these pills must go the emergency room and usually must be admitted to the hospital for at least a day. There are several types of diabetes pills, called "oral hypoglycemics", to treat Type 2 diabetes. Some names are glipizide, glyburide, and chlorpropamide, though there are many others. Some act by increasing insulin release from the pancreas. Others make it easier for cells to use glucose. All act to lower blood sugar; this is the intended effect in someone with diabetes. For young children, there is no safe dose of these drugs. Even one pill can cause a child's blood sugar to drop dangerously low, causing seizures, coma, or death. These effects may not occur for twenty-four hours and can last up to three days. This means that a child who seems fine at bedtime can have seizures during the night unless he or she is being monitored closely. Use the webPOISONCONTROL® online tool for guidance or call Poison Control immediately at 1-800-222-1222 if a child swallows a diabetes pill (or any medicine). Poison Control will tell you exactly what to do, and will guide you every step of the way. If a child does need emergency treatment, Poison Control will work with paramedics and the emergency room staff to be sure that all of the right treatment is carried out. Pills to treat diabetes should be stored in their original containers. Lock them up where children cannot see or reach them. If a child swallows even one pill, take it seriously! Don't wait to see what might happen. Use the webPOISONCONTROL online tool for guidance or call Poison Control right away. Rose Ann Gould Soloway, RN, BSN, MSEd, DABAT emerita Clinical Toxicologist References Bu Continue reading >>

Metformin Overdosage

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 Poisoning: A Complex Presentation

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 >>

Metformin Hcl

Metformin Hcl

Uses Metformin is used with a proper diet and exercise program and possibly with other medications to control high blood sugar. It is used in patients with type 2 diabetes. Controlling high blood sugar helps prevent kidney damage, blindness, nerve problems, loss of limbs, and sexual function problems. Proper control of diabetes may also lessen your risk of a heart attack or stroke. Metformin works by helping to restore your body's proper response to the insulin you naturally produce. It also decreases the amount of sugar that your liver makes and that your stomach/intestines absorb. How to use Metformin HCL Read the Patient Information Leaflet if available from your pharmacist before you start taking metformin and each time you get a refill. If you have any questions, consult your doctor or pharmacist. Take this medication by mouth as directed by your doctor, usually 1-3 times a day with meals. Drink plenty of fluids while taking this medication unless otherwise directed by your doctor. The dosage is based on your medical condition, response to treatment, and other medications you may be taking. Be sure to tell your doctor and pharmacist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products). To reduce your risk of side effects (such as upset stomach), your doctor may direct you to start this medication at a low dose and gradually increase your dose. Follow your doctor's instructions carefully. Take this medication regularly in order to get the most benefit from it. Remember to use it at the same times each day. If you are already taking another diabetes drug (such as chlorpropamide), follow your doctor's directions carefully for stopping/continuing the old drug and starting metformin. Check your blood sugar regularly a Continue reading >>

Metformin-induced Lactic Acidosis: No One Left Behind

Metformin-induced Lactic Acidosis: No One Left Behind

Abstract Metformin is a safe drug when correctly used in properly selected patients. In real life, however, associated lactic acidosis has been repeatedly, although rarely, reported. The term metformin-induced lactic acidosis refers to cases that cannot be explained by any major risk factor other than drug accumulation, usually due to renal failure. Treatment consists of vital function support and drug removal, mainly achieved by renal replacement therapy. Despite dramatic clinical presentation, the prognosis of metformin-induced lactic acidosis is usually surprisingly good. In the previous issue of Critical Care, Friesecke and colleagues demonstrate that the survival rate of patients with severe lactic acidosis due to metformin accumulation can be strikingly higher than expected based on the initial clinical evaluation [1]. Metformin is nowadays the first-line drug of choice for the treatment of adults with type 2 diabetes [2]. This drug is the sixth most frequently prescribed in the USA (> 50 million prescriptions in 2009) and is taken by almost 1.5% of the Italian population [3, 4]. Metformin is a safe drug when correctly used in properly selected patients. In particular, no cases of lactic acidosis (a relatively common side effect of other biguanide compounds) were reported in 347 trials with 70,490 patient-years of metformin use [5]. Real life can differ from research settings, however, and lactic acidosis has been repeatedly, although rarely, observed in patients treated with metformin. The number of inquiries to the Swedish Poison Information Centre for metformin intoxication has increased 10 times during the past decade, with 25 cases of severe lactic acidosis reported in 2007 and 2008 [6]. According to the American Association of Poison Control Centers, metform Continue reading >>

New Findings About What Metformin Really Does

New Findings About What Metformin Really Does

As many of my readers know, there is no requirement that the companies that sell pharmaceutical drugs provide an accurate explanation of what it is that their drugs do or of how they do it. All that they have to prove is that the drug has an impact on some measurable phenomenon. The company may claim that a drug functions using a mechanism that is later proven to be untrue. This has been the case with the SSRI drugs which it turned out actually work by remodelling the nerves in the hippocampus, NOT by changing levels of serotonin. Metformin, which has been used for decades, is another drug whose effect is well understood--it lowers blood sugar and reduces the amount of insulin needed to lower blood sugar. This has been interpreted to mean that it lowers insulin resistance. But new findings are calling this into question, as we discover that metformin may actually be stimulating insulin release or blocking the liver's release of glucose rather than impacting insulin resistant cell receptors. The first finding is one I stumbled over recently, one which seems to have gone unnoticed by the medical press. It is that metformin appears to boost GLP-1 levels. GLP-1 is an incretin hormone secreted in the gut which stimulates the beta cell to secrete insulin in the presence of high blood sugars. GLP-1 may also lower glucagon production at the same time. While Byetta and Januvia are higly promoted as being incretin drugs, some little known research suggests that metformin may also raise the level of GLP-1 in the body. Enhanced secretion of glucagon-like peptide 1 by biguanide compounds. Yasuda N et al. Biochem Biophys Res Commun. 2002 Nov 15;298(5):779-84. This was old news, but it may partially explain some of the stomach symptoms people experience with metformin. GLP-1 stops or Continue reading >>

Metformin

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 >>

Tennessee Poison Center - 03-23-17 How Does Metformin Differ From Other Oral Hypoglycemic Drugs? - Vanderbilt Health Nashville, Tn

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 >>

Metformin Feels Like Death In A Pill..

Metformin Feels Like Death In A Pill..

Registration is fast, simple and absolutely free so please,join our community todayto contribute and support the site. This topic is now archived and is closed to further replies. Well let's just say I was prepared for the stomach problems as most of you have talked about. However it has been absolutely horrid! I started my 2000mg of metformin yesterday, 1000 in the am and the rest at dinner. All I can say is oh my god! To think I felt sick before I was on meds, this just is horrible! Non stop bathroom trips, throwing up all night and this morning. My blood sugar is higher than before, probably because I can not stay hydrated. Called my dr and asked if I could start the normal dose and she won't let me lower it because my bs is too high, and made an appointment for tomorrow to check my sugar and go from there. I really do not know what to do at this point. I am missing so much work in the past week. At this point I would rather just deal with the high sugar symptoms! Sorry to hear you're having so much problems with the metformin...i'm surprised your doctor didn't start you off at the 500 mg twice daily dose the progressively increase it ---though he/she probably started you out higher as your blood sugars were so high at diagnosis. If you are taking the regular strength as opposed to the extended release pills, you might consider cutting the pills in half and spacing out your doses...say 1/2 at breakfast, 1/2 at lunch, 1/2 at dinner and 1/2 at bedtime...you'd still be getting the same TOTAL dose, just spaced differently. This might help with the symptoms, then when/if your body adjusts to the medicine, you can start just taking 2 WHOLE pills/day as directed. I did this for awhile when I was on the metformin, to stabilize my blood sugar readings. I never took more than Continue reading >>

Pharmacology And Toxicology: Treatment Of Poisons - Metformin Intoxication

Pharmacology And Toxicology: Treatment Of Poisons - Metformin Intoxication

Pharmacology and Toxicology: Treatment of Poisons - Metformin Intoxication Pharmacology and Toxicology: Treatment of Poisons - Metformin Intoxication Does this patient have metformin intoxication? Since its introduction to the US market in 1995, the biguinide, metformin has become one of the most prescribed oral hypoglycemics. It is now considered the first line agent to treat type 2 diabetes. Because of its similarity to the drug another biguinide, phenformin, there was concern that it might increase the risk of lactic acidosis as was seen in phenformin. This delayed its release in the United States and led to a number of safety studies in the 1990s. One such study compared the incidence of lactic acidosis in patients treated with metformin and found that among the 7,227 patients followed on metformin, there were no incidents of lactic acidosis reported. Following its introduction, there have been a number of comparative studies with other oral agents for diabetes showing that metformin has a superior safety profile and excellent efficacy. As per the manufacturer, metformin is contraindicated in patients with chronic kidney disease. This is defined as a creatinine 1.4 mg/dL in women and 1.5 mg/dL in men. There have been a number of studies in patients with diabetes and chronic kidney disease that show that metformin remains a very safe medication and a number of authors have argued that its use should no longer be restricted in chronic kidney disease. Other authors have argued that for consistency sake alone, metformin should be restricted by a creatinine clearance estimate as it is with most medications whose clearance depends on renal function rather than a serum creatinine. For the time being, this author recommends following the restricted use of metformin as desc Continue reading >>

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