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Incidence Of Metformin Induced Lactic Acidosis

Lactic Acidosis And The Relationship With Metformin Usage: Case Reports

Lactic Acidosis And The Relationship With Metformin Usage: Case Reports

Lactic acidosis (LA) is defined as a state of decreased systemic pH (pH <7.35) and an elevated plasma lactate concentration (>5 mmol/L). It remains the most common cause of metabolic acidosis in hospitalized patients. [1] A recent review summarized the major causes of LA and the presumed mechanisms. [2] Typically, LA is divided into disorders associated with tissue hypoxia (Cohen and Woods classification type A) and disorders in which tissue hypoxia is absent (type B). Type A LA may result from severe heart failure, sepsis, or cardiopulmonary arrest; type B can be caused by renal and hepatic failure, diabetes mellitus (DM), or drugs and toxins, including metformin, valproate, and anti-retroviral agents. [3,4] It has been reported that cardiogenic or hypovolaemic shock, severe heart failure, trauma, and sepsis are the most common causes of LA. [5] Lactate accumulation may be caused by increased production (i.e., increase glycolysis caused by hypoperfusion, hypoxaemia), decreased clearance (impaired hepatic metabolism or renal excretion), or a combination of both. [6] The exact pathophysiology of elevated lactate is likely to be the result of more than 1 condition. Many studies have shown that high lactate levels are associated with substantially increased mortality. [2,7,8] The mortality rate of LA has been reported to be between 50% and 83%. [911] DM has been also considered as one of the causes of LA. [2] The possible explanations include LA arising in patients with diabetic ketoacidosis, which is likely to be due to hypovolaemia [2] ; or reduced activity of pyruvate dehydrogenase, which may cause increased lactate levels in patients with DM independent of ketoacidosis. [12] In addition, diabetic patients with micro- or macrovascular disease are at an increased risk o Continue reading >>

Incidence Of Lactic Acidosis In Patients With Type 2 Diabetes With And Without Renal Impairment Treated With Metformin: A Retrospective Cohort Study

Incidence Of Lactic Acidosis In Patients With Type 2 Diabetes With And Without Renal Impairment Treated With Metformin: A Retrospective Cohort Study

OBJECTIVE To determine whether the use of metformin in type 2 diabetic patients with various kidney functions is associated with an increased risk of lactic acidosis (LA). RESEARCH DESIGN AND METHODS This study was a retrospective analysis of U.K. patient records from the Clinical Practice Research Datalink database from 1 January 2007 to 31 December 2012. Inclusion criteria were 1) diagnosis of type 2 diabetes before 1 January 2007, 2) treatment with metformin, and 3) at least one assessment of renal function between 2007 and 2012. Renal function was assessed by glomerular filtration rate and categorized as normal (N), mildly reduced (Mi), moderately reduced (Mo), or severely reduced (Se) function. The outcome of the study was LA. RESULTS A total of 77,601 patients treated with metformin for type 2 diabetes were identified. There were 35 LA events (10.37 [95% CI 7.22–14.42] per 100,000 patient-years) of which none were fatal and 23 were linked to a comorbidity. No significant difference in the incidence of LA was observed across N, Mi, Mo and Se renal function groups (7.6 [0.9–27.5], 4.6 [2.00–9.15], 17 [10.89–25.79], and 39 [4.72–140.89] cases per 100,000 patient-years, respectively). CONCLUSIONS The overall LA incidence rate for patients on metformin in this study was within the range of rates reported in the literature for patients with type 2 diabetes, and no significant difference was observed among patients with N, Mi, Mo, and Se function. Metformin is a widely used antihyperglycemic agent recommended by both the American Diabetes Association and the European Association for the Study of Diabetes as the first-line type 2 diabetes treatment in all patients receiving a new diagnosis, regardless of age (1). It enhances the sensitivity of both hepatic and p 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 >>

Lactic Acidosis In Diabetic Population: Is Metformin Implicated? Results Of A Matched Case-control Study Performed On The Type 2 Diabetes Population Of Grenoble Hospital University

Lactic Acidosis In Diabetic Population: Is Metformin Implicated? Results Of A Matched Case-control Study Performed On The Type 2 Diabetes Population Of Grenoble Hospital University

Copyright © 2016 Marion Lepelley et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Introduction. To evaluate the strength of association between lactic acidosis (LA) and well-recognized risk factors for LA, particularly the weight of metformin. Methods. This study is a matched case-control analysis concerning the type 2 diabetes population from Grenoble Hospital University. Cases of LA were defined biologically with pH < 7.35 and lactates > 5 mmol/L. They were matched to 2 controls defined as type 2 diabetic inpatients who did not present a LA during the study period. We performed a conditional logistic regression. Results. We included 302 cases and 604 controls; mean age was 69.5 years (SD 11.93). Intercurrent diseases were significantly associated with LA. Chronic medical conditions had a minor impact on LA incidence, except hepatocellular dysfunction. Metformin was significantly associated with a higher LA probability in case of acute kidney injury (AKI) (OR = 1.79; value = 0.020) but not in patients without AKI. Discussion and Conclusions. According to this study, metformin, compared to acute medical conditions, seemed not to be associated with LA in patients with type 2 diabetes; however in case of AKI, metformin may be associated with LA. 1. Introduction According to the World Health Organization, diabetic population should reach almost 600 million worldwide, in 2035 [1]. When medication is required, metformin is the first-line treatment in type 2 diabetes due to its superiority in reducing cardiovascular events and morbidity-mortality, compared to insulin and sulfonylureas [2–4]. Th Continue reading >>

Is Metformin Associated With Lactic Acidosis?

Is Metformin Associated With Lactic Acidosis?

Is Metformin Associated With Lactic Acidosis? The use of metformin in patients with renal impairment is associated with an increased risk for lactic acidosis. Why is this and what is the mechanism? Are sulfonylureas associated with lactic acidosis? Adjunct Faculty, Albany College of Pharmacy, Albany, New York; Clinical Pharmacy Specialist, VA Medical Center, Bath, New York Metformin is one of most commonly prescribed medications for the treatment of type 2 diabetes mellitus. Metformin exerts its activity by increasing peripheral glucose uptake and utilization, and decreasing hepatic gluconeogenesis. By decreasing pyruvate dehydrogenase activity and mitochondrial reducing agent transport, metformin enhances anaerobic metabolism and increased production of tricarboxylic acid cycle precursors. Inhibition of pyruvate dehydrogenase subsequently decreases the channeling of these precursors into aerobic metabolism and causes increased metabolism of pyruvate to lactate and ultimately lactic acid production.[ 1 ] In a patient with normal renal function, the excess lactic acid is simply cleared through the kidneys. However, in a patient with renal impairment, both metformin and lactic acid are cleared less effectively and may result in further accumulation of both.[ 1 ] The complication of lactic acidosis is serious and potentially fatal. Increased risk for lactic acidosis associated with metformin is controversial. A Cochrane Systematic Review of over 200 trials evaluated the incidence of lactic acidosis among patients prescribed metformin vs non-metformin antidiabetes medications. Of 100,000 people, the incidence of lactic acidosis was 5.1 cases in the metformin group and 5.8 cases in the non-metformin group. The authors concluded that metformin is not associated with an incre Continue reading >>

Review Metformin-associated Lactic Acidosis: Current Perspectives On Causes And Risk

Review Metformin-associated Lactic Acidosis: Current Perspectives On Causes And Risk

Abstract Although metformin has become a drug of choice for the treatment of type 2 diabetes mellitus, some patients may not receive it owing to the risk of lactic acidosis. Metformin, along with other drugs in the biguanide class, increases plasma lactate levels in a plasma concentration-dependent manner by inhibiting mitochondrial respiration predominantly in the liver. Elevated plasma metformin concentrations (as occur in individuals with renal impairment) and a secondary event or condition that further disrupts lactate production or clearance (e.g., cirrhosis, sepsis, or hypoperfusion), are typically necessary to cause metformin-associated lactic acidosis (MALA). As these secondary events may be unpredictable and the mortality rate for MALA approaches 50%, metformin has been contraindicated in moderate and severe renal impairment since its FDA approval in patients with normal renal function or mild renal insufficiency to minimize the potential for toxic metformin levels and MALA. However, the reported incidence of lactic acidosis in clinical practice has proved to be very low (< 10 cases per 100,000 patient-years). Several groups have suggested that current renal function cutoffs for metformin are too conservative, thus depriving a substantial number of type 2 diabetes patients from the potential benefit of metformin therapy. On the other hand, the success of metformin as the first-line diabetes therapy may be a direct consequence of conservative labeling, the absence of which could have led to excess patient risk and eventual withdrawal from the market, as happened with earlier biguanide therapies. An investigational delayed-release metformin currently under development could potentially provide a treatment option for patients with renal impairment pending the resu Continue reading >>

Lactic Acidosis In A Patient With Type 2 Diabetes Mellitus

Lactic Acidosis In A Patient With Type 2 Diabetes Mellitus

Introduction A 49-year-old man presented to the emergency department complaining of dyspnea for 2 days. He had a history of hypertension, type 2 diabetes mellitus, atrial fibrillation, and a severe dilated cardiomyopathy. He had been hospitalized several times in the previous year for decompensated congestive heart failure (most recently, 1 month earlier). The plasma creatinine concentration was 1.13 mg/dl on discharge. Outpatient medications included insulin, digoxin, warfarin, spironolactone, metoprolol succinate, furosemide (80 mg two times per day; increased from 40 mg daily 1 month earlier), metolazone (2.5 mg daily; added 1 month earlier), and metformin (2500 mg in three divided doses; increased from 1000 mg 1 month earlier). Physical examination revealed an obese man in moderate respiratory distress. The temperature was 36.8°C, BP was 119/83 mmHg, and heart rate was 96 per minute. Peripheral hemoglobin oxygen saturation was 97% on room air, with a respiratory rate of 26 per minute. The heart rhythm was irregularly irregular; there was no S3 or murmur. Jugular venous pressure was about 8 cm. There was 1+ edema at the ankles. A chest radiograph showed cardiomegaly and central venous prominence. The N-terminal pro-B-type natriuretic peptide level was 5137 pg/ml (reference range = 1–138 pg/ml). The peripheral hemoglobin concentration was 12.5 g/dl, the white blood cell count was 12,500/µl (76% granulocytes), and the platelet count was 332,000/µL. Initial plasma chemistries are shown in Table 1. The impression was decompensated congestive heart failure. After administration of furosemide (160 mg intravenously), the urine output increased to 320 ml over the next 1 hour. There was no improvement in the dyspnea. Within 2 hours, the patient’s BP fell to 100/64 mmHg Continue reading >>

Berberine Protects Against Metformin-associated Lactic Acidosis In Induced Diabetes Mellitus

Berberine Protects Against Metformin-associated Lactic Acidosis In Induced Diabetes Mellitus

Almani, S., Memon, I., Shaikh, T., Khoharo, H., Ujjan, I. (2017). Berberine protects against metformin-associated lactic acidosis in induced diabetes mellitus. Iranian Journal of Basic Medical Sciences, 20(5), 511-515. doi: 10.22038/ijbms.2017.8675 Suhail Ahmed Almani; Iqbal Ahmed Memon; Tariq Zaffar Shaikh; Haji Khan Khoharo; Ikramuddin Ujjan. "Berberine protects against metformin-associated lactic acidosis in induced diabetes mellitus". Iranian Journal of Basic Medical Sciences, 20, 5, 2017, 511-515. doi: 10.22038/ijbms.2017.8675 Almani, S., Memon, I., Shaikh, T., Khoharo, H., Ujjan, I. (2017). 'Berberine protects against metformin-associated lactic acidosis in induced diabetes mellitus', Iranian Journal of Basic Medical Sciences, 20(5), pp. 511-515. doi: 10.22038/ijbms.2017.8675 Almani, S., Memon, I., Shaikh, T., Khoharo, H., Ujjan, I. Berberine protects against metformin-associated lactic acidosis in induced diabetes mellitus. Iranian Journal of Basic Medical Sciences, 2017; 20(5): 511-515. doi: 10.22038/ijbms.2017.8675 Berberine protects against metformin-associated lactic acidosis in induced diabetes mellitus 1Department of Medicine Liaquat University of Medical and Health Sciences Jamshoro, Sindh, Pakistan 2Faculty of Medicine and Allied Medical Sciences Isra University, Hyderabad, Sindh, Pakistan 3Department of Pathology Liaquat University of Medical and Health Sciences Jamshoro, Sindh, Pakistan Objective(s): Causality of occurrence of metformin-associated lactic acidosis (MALA) is a clinical problem. Currently, there is no drug available to prevent MALA. The present study was conducted to evaluate the protective effect of Berberine (BBR) against MALA in induced diabetic rat model. Materials and Methods: A sample of 75 healthy male Wistar rats was randomly sele Continue reading >>

Poems & Tips From Other Journals - American Family Physician

Poems & Tips From Other Journals - American Family Physician

Metformin-Induced Lactic Acidosis Is Found to Be Rare Am Fam Physician.2004Apr15;69(8):1991. Clinical Question: What is the risk of lactic acidosis accompanying metformin therapy in patients with type 2 diabetes? Synopsis: The authors of this study combined the results of all randomized controlled trials and observational studies to determine the risk of lactic acidosis with metformin. The literature search was thorough and included unpublished data. Two independent reviewers evaluated the articles for inclusion. The methodologic quality of the studies was evaluated using modified quality criteria. Of the 194 studies in the analysis, 126 were randomized controlled studies, and 68 were observational research. More than 18,000 participants in these studies received metformin for an average of 2.1 years (36,893 patient-years). No cases of lactic acidosis were seen in the metformin-treated group or in the comparison group. Undoubtedly, patients with risk factors for lactic acidosis were not enrolled in any of the studies, and monitoring was more intense than in typical practice. Population studies estimate the incidence of lactic acidosis to be between two and nine cases per 100,000 patient-years, which also is the incidence of lactic acidosis in patients with diabetes who are not receiving metformin. Using these numbers, one to three cases of lactic acidosis would have been expected in the current study. Several studies evaluated lactic acid levels in metformin-treated patients and found no difference in baseline lactic acid levels compared with patients not treated with metformin. Bottom Line: The link between metformin and lactic acidosis, when this agent is used as prescribed, is tenuous. The bigger question is whether the risk of lactic acidosis truly increases when w Continue reading >>

Metformin-associated Lactic Acidosis In Type 2 Diabetes Mellitus: Incidence And Presentation In Common Clinical Practice

Metformin-associated Lactic Acidosis In Type 2 Diabetes Mellitus: Incidence And Presentation In Common Clinical Practice

Metformin-associated lactic acidosis in type 2 diabetes mellitus: incidence and presentation in common clinical practice Correspondence and offprint requests to: E-mail: [email protected] Search for other works by this author on: Endocrinology Service Corporaci Parc Taul Nephrology Dialysis Transplantation, Volume 23, Issue 7, 1 July 2008, Pages 24362438, Jaume Almirall, Meritxell Bricull, Jos-Miguel Gonzalez-Clemente; Metformin-associated lactic acidosis in type 2 diabetes mellitus: incidence and presentation in common clinical practice, Nephrology Dialysis Transplantation, Volume 23, Issue 7, 1 July 2008, Pages 24362438, Metformin is an oral antihyperglycaemic agent used in the treatment of type 2 diabetes mellitus. In 1998, the results of the UK Prospective Diabetes Study [ 1 ] indicated that metformin treatment is associated with a reduction in total mortality compared to other antihyperglycaemic treatments. These and other results led to its progressive widespread use. In the recent ADA-EASD consensus on management of hyperglycaemia in type 2 diabetes, metformin plus lifestyle intervention is the initial recommended therapeutic step [ 2 ]. Metformin is considered to be contraindicated in many chronic hypoxaemic conditions that may be associated with lactic acidosis (LA), such as cardiovascular, renal, hepatic, pulmonary disease and advancing age. Nevertheless, this has been a controversial matter. In a recent Cochrane review [ 3 ], pooled data from 206 comparative trials and cohort studies revealed no cases of fatal and nonfatal LA in 47846 patient-years of metformin use. Thus, the causal relationship between metformin use and LA has been questioned. Some authors have even stated that metformin's contraindications should be contraindicated in people with type 2 di Continue reading >>

Metformin-induced Lactic Acidosis: A Case Series

Metformin-induced Lactic Acidosis: A Case Series

Silvestre et al; licensee BioMed Central Ltd.2007 Unlike other agents used in the treatment of type 2 diabetes mellitus, metformin has been shown to reduce mortality in obese patients. It is therefore being increasingly used in higher doses. The major concern of many physicians is a possible risk of lactic acidosis. The reported frequency of metformin related lactic acidosis is 0.05 per 1000 patient-years; some authors advocate that this rate is equal in those patients not taking metformin. We present two case reports of metformin-associated lactic acidosis. The first case is a 77 year old female with a past medical history of hypertension and type 2 diabetes mellitus who had recently been prescribed metformin (3 g/day), perindopril and acetylsalicylic acid. She was admitted to the emergency department two weeks later with abdominal pain and psychomotor agitation. Physical examination revealed only signs of poor perfusion. Laboratory evaluation revealed hyperkalemia, elevated creatinine and blood urea nitrogen and mild leukocytosis. Arterial blood gases showed severe lactic acidemia. She was admitted to the intensive care unit. Vasopressor and ventilatory support was initiated and continuous venovenous hemodiafiltration was instituted. Twenty-four hours later, full clinical recovery was observed, with return to a normal serum lactate level. The patient was discharged from the intensive care unit on the sixth day. The second patient is a 69 year old male with a past medical history of hypertension, type 2 diabetes mellitus and ischemic heart disease who was on metformin (4 g/day), glycazide, acetylsalicylic acid and isosorbide dinitrate. He was admitted to the emergency department in shock with extreme bradycardia. Initial evaluation revealed severe lactic acidosis and Continue reading >>

Metformin-associated Lactic Acidosis Undergoing Renal Replacement Therapy In Intensive Care Units: A Five-million Population-based Study In The North-west Of Italy

Metformin-associated Lactic Acidosis Undergoing Renal Replacement Therapy In Intensive Care Units: A Five-million Population-based Study In The North-west Of Italy

Abstract Background: Metformin-associated lactic acidosis (MALA) is a severe complication of drug administration with significant morbidity and mortality. So far no study in large population areas have examined the incidence, clinical profile and outcome of acute kidney injury (AKI)-MALA patients admitted in intensive care units (ICUs) and treated by renal replacement therapy (MALA-RRT). Methods: Retrospective analysis over a 6-year period (2010-2015) in Piedmont and Aosta Valley regions (5,305,940 inhabitants, 141,174 diabetics treated with metformin) of all MALA-RRT cases. Results: One hundred and seventeen cases of AKI-MALA-RRT were observed (12.04/100,000 metformin treated diabetics, 1.45% of all RRT-ICU patients). Survival rate was 78.3%. The average duration of RRT was 4.0 days at mean dialysis effluent of 977 mL/kg/day. At admission most patients were dehydrated, and experienced shock and oliguria. Conclusion: Our data showed that MALA-RRT is a common complication, needing more prevention. Adopted policy of early, extended, continuous and high efficiency dialysis could contribute to an observed high survival rate. Video Journal Club “Cappuccino with Claudio Ronco” at © 2017 S. Karger AG, Basel Introduction Metformin, an old drug known for more than 45 years, is the first-line treatment for type 2 diabetes mellitus in the world [1]. Metformin reduces the risk of mortality and morbidity in diabetic population [2] and decreases insulin resistance [3]. Generally speaking, metformin is considered a safe drug, with some limitations. Due to increased risk of lactic acidosis, metformin is contraindicated in patients with organ dysfunction such as congestive heart failure, renal, or hepatic insufficiency, and in very elderly patients [4]. Since metformin prescription Continue reading >>

The Nephrologist's Role In Metformin-induced Lactic Acidosis

The Nephrologist's Role In Metformin-induced Lactic Acidosis

Nefrologia (English Version) 2011;31:587-90 | doi: 10.3265/Nefrologia.pre2011.Jun.10955 The nephrologist's role in metformin-induced lactic acidosis Papel del nefrlogo en la acidosis lctica grave por metformina a Secci??n de Nefrolog??a, Hospital Universitario de Guadalajara, Guadalajara, Spain, b Secci??n de Nefrolog??a, Hospital Universitario de Guadalajara, c Secci??n de Nefrolog??a, Hospital Universitario de Guadalajara. Departamento de Medicina. Universidad de Alcal??, Tab. 1. Clinical and analytical data, and treatment received by patients La metformina es un frmaco ampliamente utilizado en sujetos con diabetes mellitus y su eficacia para descender la glucemia y la hemoglobinaA1C(HbA1C) es notable. Sin embargo, en algunos pacientes, sobre todo en los que presentancomorbilidades, puede provocar una acidosis lctica grave que origina una elevada morbimortalidad. El tratamiento de esta complicacin se basa en la utilizacin de medidas de soporte y, en los casos ms graves, en procedimientos de depuracin extrarrenal, como la hemodilisis o la hemodiafiltracin continua. Metformin is an antihyperglycemic agent commonly used in diabetic patients. It is very effective and is able to reduce the plasma glucose and HbA1C. However, in some patients, specially those with comorbidities, metformin can provoke severe lactic acidosis with high morbimortality. Treatment of the lactic acidosis induced by metformin is based on the use of supportive general measures; in severe cases, procedures of extrarrenal purification like hemodialysis or continuous hemodiafiltration have been successfully used. Metformin is the main biguanide, widely used in diabetes mellitus treatment.1 It is a glycaemia-lowering agent that promotes glucose entering the tissues and reduces hepatic gluconeogenesis an Continue reading >>

Metformin-associated Lactic Acidosis: Current Perspectives On Causes And Risk.

Metformin-associated Lactic Acidosis: Current Perspectives On Causes And Risk.

Metformin-associated lactic acidosis: Current perspectives on causes and risk. University of Texas Health Science Center at San Antonio, San Antonio, TX, USA. Elcelyx Therapeutics, Inc., San Diego, CA, USA. Elcelyx Therapeutics, Inc., San Diego, CA, USA. Electronic address: [email protected] Metabolism. 2016 Feb;65(2):20-9. doi: 10.1016/j.metabol.2015.10.014. Epub 2015 Oct 9. Although metformin has become a drug of choice for the treatment of type 2 diabetes mellitus, some patients may not receive it owing to the risk of lactic acidosis. Metformin, along with other drugs in the biguanide class, increases plasma lactate levels in a plasma concentration-dependent manner by inhibiting mitochondrial respiration predominantly in the liver. Elevated plasma metformin concentrations (as occur in individuals with renal impairment) and a secondary event or condition that further disrupts lactate production or clearance (e.g., cirrhosis, sepsis, or hypoperfusion), are typically necessary to cause metformin-associated lactic acidosis (MALA). As these secondary events may be unpredictable and the mortality rate for MALA approaches 50%, metformin has been contraindicated in moderate and severe renal impairment since its FDA approval in patients with normal renal function or mild renal insufficiency to minimize the potential for toxic metformin levels and MALA. However, the reported incidence of lactic acidosis in clinical practice has proved to be very low (<10 cases per 100,000 patient-years). Several groups have suggested that current renal function cutoffs for metformin are too conservative, thus depriving a substantial number of type 2 diabetes patients from the potential benefit of metformin therapy. On the other hand, the success of metformin as the first-line diabete Continue reading >>

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 >>

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