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Metformin And Dialysis

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As you were browsing PracticeUpdate, something about your browser made us think you were a bot. There are a few reasons this might happen: You're a power user moving through this website with super-human speed. You've disabled JavaScript in your web browser. A third-party browser plugin, such as Ghostery or NoScript, is preventing JavaScript from running. Additional information is available in this . After completing the CAPTCHA below, you will immediately regain access to PracticeUpdate. ​ You reached this page when attempting to access from 35.226.183.143 on 2018-01-06 18:18:13 UTC. Trace: 8d3497e3-c874-476e-b444-70710053403c via f142fe30-0da7-428a-92b2-8a74e399b4ec Continue reading >>

Fda Issues Guidance For Metformin Use In Renal Impairment

Fda Issues Guidance For Metformin Use In Renal Impairment

FDA Issues Guidance for Metformin Use in Renal Impairment The FDA has issued new guidance for the use of the first-line diabetes drug metformin in patients with renal impairment. Metformin was approved by the FDA in 1994 for the management of type 2 diabetes. Since its approval, its labeling has warned of a contraindication in elevated serum creatinine (>1.5 mg/dL for males, >1.4 mg/dL for females) due to a risk of lactic acidosis secondary to metformin accumulation.1 Other risk factors for lactic acidosis include contrast dye exposure within 48 hours, chronic or excessive alcohol intake, dehydration, sepsis, acute congestive heart failure, and age. This absolute contraindication was based on clinical trials of an older biguanide called phenformin, which showed a greater risk of lactic acidosis associated with significant mortality and was subsequently pulled off the market in 1977.2 Although phenformin is no longer available in the United States, its still available in European and South American markets. Notably, the incidence of lactic acidosis associated with metformin is as low as 0.03 cases per 1000 patient-years. The FDA reviewed several studies to determine whether patients with mild to moderate renal impairment could safely continue on metformin to manage their type 2 diabetes. One of the larger trials reviewed was an observational study of 51,675 type 2 diabetes patients to determine the effect metformin would have on primary outcomes of cardiovascular disease (CVD), all-cause mortality, and acidosis or serious infections with varying degrees of renal function.3 Based on subgroup analyses of patients with varying degrees of renal impairment, the investigators determined that patients with an estimated glomerular filtration rate (eGFR) >45 mL/min/m2 showed no Continue reading >>

Should Dialysis Be Offered In All Cases Of Metformin-associated Lactic Acidosis?

Should Dialysis Be Offered In All Cases Of Metformin-associated Lactic Acidosis?

Should dialysis be offered in all cases of metformin-associated lactic acidosis? Metformin is commonly used in diabetes mellitus type 2, with lactic acidosis being a rare but potentially fatal complication of this therapy. The management of metformin-associated lactic acidosis (MALA) is controversial. Treatment may include supportive care, activated charcoal, bicarbonate infusion, hemodialysis, or continuous venovenous hemofiltration. In the previous issue of Critical Care, Peters and colleagues systematically evaluated outcomes in MALA patients admitted to their intensive care unit. The mortality rate of patients who received dialysis was similar to that of patients who were not dialyzed. However, it was the more acutely and chronically ill patients who actually received dialysis. This suggests that hemodialysis was beneficial in preventing a higher mortality rate in those who required renal replacement therapy. Diabetes Mellitus TypeMetforminRenal Replacement TherapyAcute Kidney InjuryActivate Charcoal The literature on the management of metformin-associated lactic acidosis (MALA) is sparse and consists of case reports and case series. In the previous issue of Critical Care, Peters and colleagues [ 1 ] presented a retrospective cohort study in patients with MALA. This study represents an important step forward in systematically evaluating outcomes in this rare but serious condition. Metformin is commonly used in type 2 diabetes mellitus and accounts for approximately one third of all prescriptions for oral hypoglycemic agents in the US [ 2 ]. The United Kingdom Prospective Diabetes Study demonstrated impressive reductions in diabetes-related endpoints and mortality in overweight patients with type 2 diabetes who used this drug [ 3 ]. A rare but extremely serious adve Continue reading >>

Common Oral Diabetes Medications

Common Oral Diabetes Medications

Disclaimer: This article is for informational purposes only and is not intended to be a substitute for medical advice or diagnosis from a physician. Diabetes is a growing epidemic in the United States and is the number-one cause of chronic kidney disease (CKD) and end stage renal disease (ESRD). Glucose is a major source of energy for the cells in muscles and tissues, including the brain. For glucose to be utilized by these cells, insulin — a hormone secreted by the pancreas — is necessary. A person with diabetes either does not make insulin or is resistant to the insulin his/her body produces, resulting in high blood sugar levels. Type 1 diabetes, also called insulin-dependent diabetes, is caused by the body’s failure to produce insulin and requires insulin injections. People with type 2 diabetes make insulin, but their bodies are resistant to it. Treatment usually comprises of oral diabetes medications, insulin, diet or a combination of these. The following is a list of the most common oral medicines for controlling blood sugar levels. Please note:People with CKD and ESRD should always consult their nephrologist before taking any medications or changing prescribed doses. Sulfonylureas Similar to meglitinides, sulfonylureas stimulate the pancreas to secrete more insulin, but the insulin secretion is not related to increasing blood sugar levels. These drugs are therefore more likely to cause low blood sugar levels or hypoglycemia. Common sulfonylureas are Micronase®(glyburide), Glucotrol®(glipizide) and Amaryl®(glimepiride). Glyburide use should be avoided in patients with severe kidney impairment as defined by a GFR of less than 60 mL/min (CKD stage 3 and below). Because 50 percent of the glyburide is excreted by the kidneys, the drug can build up in people wi Continue reading >>

Metformin - Glucophage - Renal Dosing

Metformin - Glucophage - Renal Dosing

Usual starting dose: 500mg po bid or 850 mg po qd. Dosage increases should be made in increments of 500 mg weekly or 850 mg q2 weeks, up to a total of 2000 mg per day, given in divided doses. (Maximum: 2550mg/day). Glucophage XR: Starting dose: 500 mg qd with the evening meal. Dosage increases should be made in increments of 500 mg weekly, up to a maximum of 2000 mg daily with the evening meal. Contraindicated: Males with a serum creatinine > 1.5 mg/dl or females >1.4 mg/dl. Also patients with an abnormal creatinine clearance (~ <60-70 ml/min). National Institutes of Health, U.S. National Library of Medicine, DailyMed Database. Provides access to the latest drug monographs submitted to the Food and Drug Administration (FDA). Please review the latest applicable package insert for additional information and possible updates. A local search option of this data can be found here . The authors make no claims of the accuracy of the information contained herein; and these suggested doses are not a substitute for clinicaljudgment. Neither GlobalRPh Inc. nor any other party involved in thepreparation of this program shall be liable for any special, consequential, or exemplary damages resulting in whole or part from any user's use of or reliance upon this material.PLEASE READ THE DISCLAIMER CAREFULLY BEFORE ACCESSING OR USING THIS SITE. BY ACCESSING OR USING THIS SITE, YOU AGREE TO BE BOUND BY THE TERMS AND CONDITIONS SET FORTH IN THE DISCLAIMER. Readthe disclaimer Continue reading >>

Inadvertent Use Of Metformin In A Peritoneal Dialysis Patient: Case Report And Literature Review

Inadvertent Use Of Metformin In A Peritoneal Dialysis Patient: Case Report And Literature Review

Received Date: April 14, 2014; Accepted Date: June 11, 2015; Published Date: June 17, 2015 Citation: Tumma A, Tan KS (2015) Inadvertent Use of Metformin in a Peritoneal Dialysis Patient: Case Report and Literature Review. J Nephrol Ther 5:204. doi:10.4172/2161-0959.1000204 Copyright: 2015 Tumma A, 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. Background: Metformin has been a main stay medication in the treatment of type 2 diabetes mellitus. However, its use has been limited by its potential risk of metabolic acidosis in chronic kidney disease. Although this been anecdotally proposed, there have been no studies suggesting the effects of metformin in end stage renal failure, especially in the setting of peritoneal dialysis. We submit a case of metformin inadvertently used in end stage renal failure, without evidence of metabolic acidosis. Case presentation: A 54 year old man with known type 2 diabetes mellitus presented late to our service with end stage renal failure. He had been on metformin at time of diagnosis of end stage renal failure. Although initially ceased on admission, metformin was inadvertently restarted on discharge from another hospital where he had been transferred for a tenchkoff catheter insertion. This issue was only realised 10 days later following an incidental medication review. He had already commenced peritoneal dialysis at this stage. He was asymptomatic and there was no evidence of metabolic acidosis. We hypothesise that Metformin use in end stage renal failure with dialysis may not be as harmful. To our knowledge, this is the first case report sugges Continue reading >>

Using Metformin In The Presence Of Renal Disease

Using Metformin In The Presence Of Renal Disease

Using metformin in the presence of renal disease Using metformin in the presence of renal disease BMJ 2015; 350 doi: (Published 14 April 2015) Cite this as: BMJ 2015;350:h1758 Tahseen A Chowdhury, consultant in diabetes, M Magdi Yaqoob, professor in clinical nephrology 1Departments of Diabetes and Nephrology, Barts and the London School of Medicine and Dentistry, London E1 1BB, UK. Correspondence to: T Chowdhury Tahseen.Chowdhury{at}bartshealth.nhs.uk Current guidelines are too restrictive, and many patients who could benefit are missing out In January, the electronic Medicines Compendium (eMC) updated the Summary of Product Characteristics for Glucophage (metformin), approved by the UK Medicines and Healthcare Products Regulatory Agency (MHRA). The summary states that Metformin may be used in patients with moderate renal impairment, stage 3a (creatinine clearance [CrCl] 45-59 mL/min or estimated glomerular filtration rate [eGFR] 45-59 mL/min/1.73 m2) only in the absence of other conditions that may increase the risk of lactic acidosis . . . If CrCl or eGFR fall <45 mL/min or <45 mL/min/1.73 m2 respectively, metformin must be discontinued immediately.1 This is reiterated in the patient information leaflet. Interestingly, the summary for generic metformin states that Renal failure or renal dysfunction (creatinine clearance <60 ml/min) is a contraindication to use. In the face of burgeoning levels of type 2 diabetes and associated renal disease, we believe that this restriction is too conservative and will deny an important drug to many thousands of people with diabetes who Continue reading >>

Metformin In Peritoneal Dialysis: A Pilot Experience

Metformin In Peritoneal Dialysis: A Pilot Experience

Metformin in Peritoneal Dialysis: A Pilot Experience Department of Internal Medicine,1 King Fahd University Hospital, University of Dammam, and Department of Clinical Pharmacology,2 University of Dammam, Khobar, Saudi Arabia, and Division of Renal Medicine,3 Clintec, Karolinska Institute, Stockholm, Sweden Correspondence to: A.K. Al-Hwiesh, Department of Internal Medicine, King Fahd University Hospital, Al-Khobar 31952 Saudi Arabia. dralhwiesh{at}yahoo.com Objective: In a number of patients, the antidiabetic drug metformin has been associated with lactic acidosis. Despite the fact that diabetes mellitus is the most common cause of end-stage renal disease (ESRD) and that peritoneal dialysis (PD) is an expanding modality of treatment, little is known about optimal treatment strategies in the large group of PD patients with diabetes. In patients with ESRD, the use of metformin has been limited because of the perceived risk of lactic acidosis or severe hypoglycemia. However, metformin use is likely to be beneficial, and PD might itself be a safeguard against the alleged complications. Methods: Our study involved 35 patients with insulin-dependent type 2 diabetes [median age: 54 years; interquartile range (IQR): 47-59 years] on automated PD (APD) therapy. Patients with additional risk factors for lactic acidosis were excluded. Metformin was introduced at a daily dose in the range 0.5 - 1.0 g. All patients were monitored for glycemic control by blood sugar levels and HbA1c. Plasma lactic acid levels were measured weekly for 4 weeks and then monthly to the end of the study. Plasma and effluent metformin and plasma lactate levels were measured simultaneously. Results: In this cohort, the median duration of diabetes was 18 years (IQR: 14 - 21 years), median time on PD was 31 mo Continue reading >>

Clinical Research Extending Metformin Use In Diabetic Kidney Disease: A Pharmacokinetic Study In Stage 4 Diabetic Nephropathy

Clinical Research Extending Metformin Use In Diabetic Kidney Disease: A Pharmacokinetic Study In Stage 4 Diabetic Nephropathy

Metformin use in advanced chronic kidney disease is controversial. This study sought to examine the pharmacokinetics, safety, and efficacy of low-dose metformin in patients with type 2 diabetes and stage 4 chronic kidney disease. In this open-label, phase I trial, 3 consecutive cohorts (1, 2, and 3) of 6 patients each were recruited to receive 250-, 500-, or 1000-mg once-daily doses of metformin, respectively. All patients underwent a first-dose pharmacokinetic profile and weekly trough metformin concentrations for the duration of 4 weeks of daily therapy. Prespecified clinical and biochemical safety endpoints of serum bicarbonate, venous pH, and serum lactate were assessed weekly. Efficacy was assessed by pre- and post-HbA1c and 72-hour capillary glucose monitoring. There was no evidence of accumulation of metformin in any cohort. There were no episodes of hyperlactatemia or metabolic acidosis and no significant change in any biochemical safety measures. Median (interquartile range) observed trough concentrations of metformin in cohorts 1, 2, and 3 were 0.083 (0.121) mg/l, 0.239 (0.603) mg/l, and 1.930 (3.110) mg/l, respectively. Average capillary glucose concentrations and mean HbA1c decreased in all cohorts. In our patient cohorts with diabetes and stage 4 chronic kidney disease, treatment with 4 weeks of low-dose metformin was not associated with adverse safety outcomes and revealed stable pharmacokinetics. Our study supports the liberalization of metformin use in this population and supports the use of metformin assays for more individualized dosing. Continue reading >>

Metabolic Effects Of Metformin In Patients With Acute Renal Failure

Metabolic Effects Of Metformin In Patients With Acute Renal Failure

Metformin use has been associated with significant disturbances in acid-base balance. Metformin remains the first-line therapy for majority of patients with type 2 diabetes mellitus. Its metabolic effects have provided great support for its use in diabetes management. However, risks of renal impairment and lactic acidosis have always warranted close monitoring in patients with predisposing factors to these events. In fact, lactic acidosis has been associated with renal impairment. Metformin is not metabolized in the liver and is excreted by active tubular secretion. The risk of developing lactic acidosis greatly depends on the magnitude of each patient’s renal impairment and their age. Nonetheless, these studies fail to take into consideration those patients with renal failure. The majority of trials out there exclude patients with renal defects due to its nephrotoxic potential. The nephrotoxicity of increased levels of metformin relies on its effect on renal mitochondrial activity. Previous studies have demonstrated that therapeutic doses of metformin are not associated with risk of lactic acidosis. Renal mitochondrial dysfunction can lead to tubular cell ischemia and increased lactic acid production. Hence, those patients with renal impairment will warrant closer monitoring and dose optimization strategies to prevent these complications while obtaining optimal glucose control. Recently, renal dose adjustments changed. Now patients are to be monitored based on glomerular filtration rate and not serum creatinine for metformin therapy. A recent study conducted by David Cucchiari and colleagues evaluated the dose-related effects of metformin on acid-base balance in patients with diabetes who develop acute renal failure. In this cross-sectional study, 126 patients were i Continue reading >>

Be Cautious Of Metformin Use In Chronic Kidney Disease Patients

Be Cautious Of Metformin Use In Chronic Kidney Disease Patients

Be cautious of metformin use in chronic kidney disease patients Be cautious of metformin use in chronic kidney disease patients In specific situations, clinicians should monitor a patient's metformin use in order to prevent dialysis and higher risk of kidney failure. We often hear from endocrine that metformin rarely causes lactic acidosis and that nephrology is a worrywart. In reality, we do see cases of lactic acidosis due to metformin. Many of these patients are hospitalized so often that endocrine is not following them at the time. Recently we had a 64-year-old female who was admitted to the hospital due to nausea and vomiting with confusion. She had a history of mild chronic kidney disease (CKD); had diabetes, which was being treated with metformin; and was on an angiotensin-converting enzyme (ACE) inhibitor along with a fluid pill (patient's description). Even though she had picked up her grandchild's gastrointestinal bug and could not hold food down, the patient faithfully took her medications each day. For the fever and generalized aches and pains from the flu, she added naproxen. Between the lack of intake, the insults to the kidneys in the form of medications, and the dehydration from the virus and the fluid pill, the patient had a pH of 7.17 (normal: 7.4), a lactic acid of 9 (<2.3 mmol/L), and a serum creatinine of 8 (0.6 to 1.1 mg/dL). Although we immediately initiated intravenous bicarbonate and fluids, the patient ultimately required dialysis. While she eventually came off the dialysis and recovered from the acute kidney injury, she is at higher risk of kidney failure in the future. All of this could have been prevented by taking this patient off metformin at an earlier stage. (191-1) Kim Zuber, PA-C,oversees patients in 7 dialysis centers for Metropolita 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 >>

Changes In Metformin Use In Chronic Kidney Disease

Changes In Metformin Use In Chronic Kidney Disease

Background Glucose-lowering biguanides were discovered in the 1920s. One of these was metformin (dimethylbiguanide), but it was then forgotten [1]. The first human trial on biguanides that used the name Glucophage (glucose eater) was published in 1957 [2]. In the next couple of years reports were published on phenformin [3] and buformin [4]. However, due to their association with lactic acidosis (LA), both phenformin and buformin were withdrawn from many countries. Similar concerns were raised for metformin, but it remained on the market and has been available in the UK since 1958, although it only became available in the USA in 1994. Clinical benefits in diabetes mellitus type 2 Metformin acts primarily in the liver by reducing glucose output and also by enhancing peripheral uptake of glucose, mainly in muscles. It is not generally associated with a risk of hypoglycemia unless there is excessive exercise, severe calorie reduction or when mixed with other antidiabetic medicine. There is absence of weight gain along with modest reductions in triglycerides [5]. It causes a reduction in mortality by decreasing cardiovascular complications [6]. Metformin has shown some effectiveness in polycystic ovarian syndrome, some gynecological cancers, nonalcoholic fatty liver disease and for premature puberty. However, its main role remains in the management of diabetes mellitus type 2 (DM2). The International Diabetes Federation lists it as one of the first antidiabetic medicines to be used for DM2 [7]. The World Health Organization lists it as one of two essential medicines for diabetes [8]. Fear of LA Metformin is chemically similar to phenformin, but has a different mechanism of action. Although the fear of LA remains, no absolute definitive causal relationship has been proven be Continue reading >>

Management Of Hyperglycemia In Patients With Type 2 Diabetes And Pre-dialysis Chronic Kidney Disease Or End-stage Renal Disease

Management Of Hyperglycemia In Patients With Type 2 Diabetes And Pre-dialysis Chronic Kidney Disease Or End-stage Renal Disease

The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc. INTRODUCTION — Chronic kidney disease (CKD) is associated with insulin resistance and, in advanced CKD, decreased insulin degradation. The latter can lead to a marked decrease in insulin requirement or even the cessation of insulin therapy in patients with type 2 diabetes. Both of these abnormalities are at least partially reversed with the institution of dialysis. (See "Carbohydrate and insulin metabolism in chronic kidney disease".) Because of the uncertainty in predicting insulin requirements, careful individualized therapy is essential among patients who have advanced CKD or are initiating dialysis. The insulin requirement in any given patient depends upon the net balance between improving tissue sensitivity and restoring normal hepatic insulin metabolism. In addition, among patients on peritoneal dialysis, glucose contained in peritoneal dialysate tends to increase the need for diabetes therapy. Changes in dietary intake and exercise (ie, reduced intake due to anorexia prior to starting dialysis) can also affect the response to administered insulin. Furthermore, the uremic environment can affect methods used to assess glycemic control, and the metabolism of most oral diabetes agents is prolonged, making them more difficult to use. This topic reviews glycemic targets, methods of monitoring glycemic control, and suggested treatment regimens for patients on hemodialysis and peritoneal dialysis. The treatment of diabetes Continue reading >>

Metformin And Patients On Dialysis

Metformin And Patients On Dialysis

See the article " Prescribing for patients on dialysis " onpage21. I enjoyed reading the concise, well-referenced summary on prescribing for patients on dialysis. 1 However, the statement Metformin is contraindicated due to the risk of lactic acidosis is not referenced and is perhaps not supported by the available evidence. A Cochrane review on the risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes concluded that there is no evidence at present that metformin is associated with an increased risk for lactic acidosis when prescribed under the study conditions. 2 The authors commented that of the 334 prospective studies, 143 (53%) allowed for the inclusion of renal insufficiency, following 37 360 patient-years of metformin use. One trial in the review questioned the standard contraindications by studying 393 patients, all with at least one contraindication to metformin use, and found no cases of lactic acidosis over four years. 3 All of the patients had renal insufficiency, with mean plasma creatinine concentrations of 1.52.5 mg/dL (mean 1.8 mg/dL). A review of metformin in chronic kidney disease nicely summarises the issue. 4 It cites two small studies of metformin use in dialysis patients and recommends 250 mg daily for peritoneal dialysis patients and 500 mg after each dialysis session for those receiving haemodialysis. Metformin is renally excreted and in overdose has been seen to cause lactic acidosis without other contributory comorbidity. While there are grounds for caution in patients on dialysis, an increased risk of lactic acidosis has not been specifically established. Many renal physicians choose to administer metformin in reduced doses to selected patients with end-stage renal disease because of its proven efficacy in the managem Continue reading >>

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