diabetestalk.net

Metformin Renal Dosing Ada

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 >>

Support Article

Support Article

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 >>

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 >>

Why Is Metformin Contraindicated In Chronic Kidney Disease?

Why Is Metformin Contraindicated In Chronic Kidney Disease?

To the Editor: In their article about the care of patients with advanced chronic kidney disease, Sakhuja et al1 mentioned that metformin is contraindicated in chronic kidney disease. Metformin is a good and useful drug. Not only is it one of the cheapest antidiabetic medications, it is the only one shown to reduce cardiovascular mortality rates in type 2 diabetes mellitus. Although metformin is thought to increase the risk of lactic acidosis, a Cochrane review2 found that the incidence of lactic acidosis was only 4.3 cases per 100,000 patient-years in patients taking metformin, compared with 5.4 cases per 100,000 patient-years in patients not taking metformin. Furthermore, in a large registry of patients with type 2 diabetes and atherothrombosis,3 the rate of all-cause mortality was 24% lower in metformin users than in nonusers, and in those who had moderate renal impairment (creatinine clearance 30–59 mL/min/1.73 m2) the difference was 36%.3 A trial by Rachmani et al4 raised questions about the standard contraindications to metformin. The authors reviewed 393 patients who had at least one contraindication to metformin but who were receiving it anyway. Their serum creatinine levels ranged from 1.5 to 2.5 mg/dL. There were no cases of lactic acidosis reported. The patients were then randomized either to continue taking metformin or to stop taking it. At 2 years, the group that had stopped taking it had gained more weight, and their glycemic control was worse. In the Cochrane analysis,2 although individual creatinine levels were not available, 53% of the studies reviewed did not exclude patients with serum creatinine levels higher than 1.5 mg/dL. This equated to 37,360 patient-years of metformin use in studies that included patients with chronic kidney disease, and did Continue reading >>

Use Of Metformin In The Setting Of Mild-to-moderate Renal Insufficiency

Use Of Metformin In The Setting Of Mild-to-moderate Renal Insufficiency

ADVANTAGES OF METFORMIN There is some evidence that early treatment with metformin is associated with reduced cardiovascular morbidity and total mortality in newly diagnosed type 2 diabetic patients (4). However, the data come from a small subgroup of a much larger trial. In contrast, despite multiple trials of intensive glucose control using a variety of glucose-lowering strategies, there is a paucity of data to support specific advantages with other agents on cardiovascular outcomes (5–7). In the original UK Prospective Diabetes Study (UKPDS), 342 overweight patients with newly diagnosed diabetes were randomly assigned to metformin therapy (8). After a median period of 10 years, this subgroup experienced a 39% (P = 0.010) risk reduction for myocardial infarction and a 36% reduction for total mortality (P = 0.011) compared with conventional diet treatment. Similar benefits were not observed in those randomly assigned to sulfonylurea or insulin. In an 8.5-year posttrial monitoring study, after participants no longer were randomly assigned to their treatments, individuals originally assigned to metformin (n = 279) continued to demonstrate a reduced risk for both myocardial infarction (relative risk 33%, P = 0.005) and total mortality (relative risk 27%, P = 0.002) (9). The latter results are even more impressive when one considers that HbA1c levels in all initially randomly assigned groups had converged within 1 year of follow-up. Unlike sulfonylureas, thiazolidinediones, and insulin, metformin is weight neutral (10), which makes it an attractive choice for obese patients. Furthermore, the management of type 2 diabetes can be complicated by hypoglycemia, which can seriously limit the pursuit of glycemic control. Here, too, metformin has advantages over insulin and some Continue reading >>

Metformin And Renal Function

Metformin And Renal Function

etformin is first-line therapy for the management of type 2 diabetes mellitus, based on the American Diabetes Association and American College of Clinical Endocrinology guidelines. Unless there is a contraindication, metformin should be considered part of a patient’s regimen for type 2 diabetes mellitus. A controversial contraindication for metformin is renal disease or dysfunction. Absolute cut-offs in serum creatinine has been published as times to discontinue metformin therapy (≥1.4 mg/dL for women; ≥1.5 mg/dL for men). Lipska KL, et al, published recommendations for metformin among patients with mild to moderate renal dysfunction. This publication has been used in clinical practice to support “relaxed” dosing of metformin. Based on this publication in Diabetes Care (2011), the following recommendations were suggested: For patients with estimated glomerular filtration rate (eGFR) above 60, then metformin can be continued and renal function should be monitored on an annual basis. For patients with eGFR between 45 and 60, then metformin can be continued but the frequency of monitoring increases to every 3 or 6 months. For patients with eGFR between 30 and 45, there are several options depending on the individual. These options include lowering the dose by 50%; increasing the monitoring of renal function; or discontinuing metformin. For patients with a baseline eGFR 30 and 45, metformin should not be initiated. For patients with eGFR less than 30, then metformin should be stopped (if prescribed) or not initiated (if considered for new patients). As diabetes educators, it is essential to check package inserts and/or drug references for the method (CrCl or eGFR) to assess renal function and appropriate dose adjustments. On Friday, April 8, the Food and Drug Admi Continue reading >>

Fda Issues Guidance For Metformin Use In Renal Impairment

Fda Issues Guidance For Metformin Use In Renal Impairment

Chris Tanski received his PharmD from the University at Buffalo School of Pharmacy and Pharmaceutical Sciences and is now working as a clinical staff pharmacist for Pinnacle Health in Harrisburg, Pennsylvania. He entered the field of hospital pharmacy directly from school, and he was one of the first to pilot a decentralized pharmacist role in the hospital. His other notable work contributions include working on palliative projects and transition of care for COPD patients. Chris was an editor and contributor to a film theory blog, a sketch comedy writer throughout pharmacy school, and he has a significant amount of experience writing drug information papers on neurology and infectious disease topics for both school and work. 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, it’s 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 10 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. Figure 2. Safety profile (venous lactate, bicarbonate, and pH) in all 3 cohorts across the study period. Venous lactate for patient 11 appears as a dotted line. Patients 2 and 19 commenced metformin therapy a few days Continue reading >>

Metformin Use Among Patients With Type 2 Diabetes And Renal Impairment

Metformin Use Among Patients With Type 2 Diabetes And Renal Impairment

Metformin Use among Patients with Type 2 Diabetes and Renal Impairment The most prescribed oral anti The most prescribed oral antidiabetic medication for treating type 2 diabetes (T2D), metformin is contraindicated in T2D patients with renal impairment due to risk of lactic acidosis. Metformin use among T2D patients with renal impairment was examined in a retrospective analysis of the I3 Innovus database from May 1, 2000-December 31, 2008. T2D patients (ICD-9 codes 250.x0 or 250.x2) with renal impairment (serum creatinine concentration [ge]1.5 mg/mL in males and [ge]1.4 mg/mL in females) were identified. Stage of chronic kidney disease (CKD) was based on estimated glomerular filtration rate (eGFR), calculated from serum creatinine, age and gender (using MDRD formula). The index date was the same or later diagnosis date of T2D or CKD. The baseline period was 6 months prior to index date, and the follow-up period was 12 months after index date. Patients were [ge]18 yrs and had at least one serum creatinine value and at least one claim for antidiabetic medications during the study period. Patients with type 1 diabetes were excluded. After applying all inclusion and exclusion criteria to 1.7 million T2D patients, a total of 1,985 patients were identified with CKD and T2D; the majority (76%) had stage 3 CKD. Mean age was 61 years, and two-thirds were male. In the follow-up period after diagnosis of T2D and renal impairment, 666 (34%) were prescribed metformin. Metformin use was highest in CKD stage 2, followed by stages 3 and 5 (table). Patients [lt]65 years more often received metformin than those [ge]65 years (37% vs. 27%, p[lt]0.0001). Metformin use between female (34%) and male patients (33%) was similar (p=0.8175). Metformin was maintained in T2D patients with varying 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 >>

In Brief: New Recommendations For Use Of Metformin In Renal Impairment

In Brief: New Recommendations For Use Of Metformin In Renal Impairment

The FDA has required labeling changes that replace serum creatinine (SCr) with estimated glomerular filtration rate (eGFR) as the parameter used to determine the appropriateness of treatment with the biguanide metformin (Glucophage, and others) in patients with renal impairment. These changes will allow more patients with mild to moderate renal impairment to receive metformin, which is generally the first drug prescribed for treatment of type 2 diabetes. Metformin was previously contraindicated in women with a SCr level ≥1.4 mg/dL and in men with a SCr level ≥1.5 mg/dL, but use of SCr as a surrogate indicator tends to underestimate renal function in certain populations (e.g., younger patients, men, black patients, patients with greater muscle mass). The calculation of eGFR takes into account age, race, and sex, as well as SCr level, providing a more accurate assessment of kidney function. A literature review summarized in an FDA Drug Safety Communication concluded that, based on eGFR, metformin is safe to use in patients with mild renal impairment and in some patients with moderate renal impairment.1 The eGFR should be calculated before patients begin treatment with metformin and at least annually thereafter. Metformin is now contraindicated in patients with an eGFR <30 mL/min/1.73 m2, and starting treatment with the drug in patients with an eGFR between 30 and 45 mL/min/1.73 m2 is not recommended. If the eGFR falls below 45 mL/min/1.73 m2 in a patient already taking metformin, the benefits and risks of continuing treatment should be assessed. Metformin should be not be administered for 48 hours after an iodinated contrast imaging procedure in patients with an eGFR <60 mL/min/1.73 m2 or a history of liver disease, alcoholism, or heart failure, or in those receiving Continue reading >>

Metformin - Nice Guidance Regarding Renal Function - General Practice Notebook

Metformin - Nice Guidance Regarding Renal Function - General Practice Notebook

metformin - NICE guidance regarding renal function start metformin treatment in a person who is overweight or obese (tailoring the assessment of body-weight-associated risk according to ethnic group ) and whose blood glucose is inadequately controlled by lifestyle interventions (nutrition and exercise) alone metformin should be considered as an option for first-line glucose-lowering therapy for a person who is not overweight metformin should be continued if blood glucose control remains or becomes inadequate and another oral glucose-lowering medication is added the dose of metformin should be stepped up gradually over weeks to minimise risk of gastro-intestinal (GI) side effects. Consider a trial of extended-absorption metformin tablets where GI tolerability prevents continuation of metformin therapy in adults with type 2 diabetes, review the dose of metformin if the estimated glomerular filtration rate (eGFR) is below 45 ml/minute/1.73m2: Stop metformin if the eGFR is below 30 ml/minute/1.73m2 Prescribe metformin with caution for those at risk of a sudden deterioration in kidney function and those at risk of eGFR falling below 45ml/minute/1.73m2 benefits of metformin therapy should be discussed with a person with mild to moderate liver dysfunction or cardiac impairment so that: due consideration can be given to the cardiovascular-protective effects of the drug (1) an informed decision can be made on whether to continue or stop the metformin Continue reading >>

Changes In Metformin Use In Chronic Kidney Disease

Changes In Metformin Use In Chronic Kidney Disease

Go to: 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 beyond doubt. Many reported cases of metformin-associated LA (MALA) did not measure metformin levels, whereas in others levels were not high, suggesting ‘metformin coincident lactic acidosis’ [9]. In 1998, Misbin et al. reported that after starting to use metformin, rates of LA in the USA were no different from prior to the approval of metformin [10]. Many reported cases of LA had multiple risk factors besides renal failure. Since DM2 is a risk factor, it is thought that many such cases may have been just from DM2. The putative risk factors for LA described in the literature include old age, decreased cardiac output, respiratory failure or hypoxic conditions, ethanol intoxication, fasting and decreased hepatic function. In a nested case–control analysis that included 50 048 patients, six patients were identified with active use of metformin and LA. Out of those, five patients had sepsis and signs of end-organ damage, suggesting that LA most frequently occurs in acutely worsening clinical scenarios [11]. Continue reading >>

Metformin Use Being Limited?

Metformin Use Being Limited?

Current black box warning may be overstating the kidney risk. Metformin—the blockbuster drug utilized as the primary agent to treat patients with type 2 diabetes—may potentially be hindered in usage due to its current prescribing grounds. Despite its establishment as the first-line therapy for type 2 diabetes, about one-half of the patients currently in the United States do not take it. A major proponent of this is its current labeling, which expresses unjustifiable concerns about its use for treatment in those with mild to moderate renal insufficiency. The current label carries a contraindication against use of metformin when serum creatinine levels exceed 1.4mg/dL in women or 1.5mg/dL in men. Over the past few years, clinicians throughout the country have come to an overwhelming consensus that the US Food and Drug Administration (FDA) labeling for metformin could be more lenient and also that it can be expressed in the more precise estimated glomerular filtration rates (eGFRs), rather than serum creatinine. The FDA’s initial rationale behind the label was due to resilient evidence that phenformin caused lactic acidosis (another biguanide which has been removed from the US market). Metformin is cleared from the body via the kidneys and for patients with significant renal failure, there were increasing concerns that metformin could potentially build up to relatively high levels that could leave patients to have lactic acidosis. There is now an overwhelming two decades’ worth of research and evidence showing no serious increased risks for lactic acidosis in patients with mild-to-moderately impaired renal function. The American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) have furthermore supported the removal of restric Continue reading >>

Risks Of Metformin In Type 2 Diabetes And Chronic Kidney Disease: Lessons Learned From Taiwanese Data

Risks Of Metformin In Type 2 Diabetes And Chronic Kidney Disease: Lessons Learned From Taiwanese Data

Abstract Like other biguanide agents, metformin is an anti-hyperglycemic agent with lower tendency towards hypoglycemia compared to other anti-diabetic drugs. Given its favorable effects on serum lipids, obese body habitus, cardiovascular disease, and mortality, metformin is recommended as the first-line pharmacologic agent for type 2 diabetes in the absence of contraindications. However, as metformin accumulation may lead to type B non-hypoxemic lactic acidosis, especially in the setting of kidney injury, chronic kidney disease, and overdose, regulatory agencies such as the United States Food and Drug Administration (FDA) have maintained certain restrictions regarding its use in kidney dysfunction. Case series have demonstrated a high fatality rate with metformin-associated lactic acidosis (MALA), and the real-life incidence of MALA may be underestimated by observational studies and clinical trials that have excluded patients with moderate-to-advanced kidney dysfunction. A recent study of advanced diabetic kidney disease patients in Taiwan in Lancet Endocrinology and Diabetes has provided unique insight into the potential consequences of unrestricted metformin use, including a 35% higher adjusted mortality risk that was dose-dependent. This timely study, as well as historical data documenting the toxicities of other biguanides, phenformin and buformin, suggest that the recent relaxation of FDA recommendations to expand metformin use in patients with kidney dysfunction (i.e., those with estimated glomerular filtration rates ≥30 instead of our recommended ≥45 ml/min/1.73 m2) may be too liberal. In this article, we will review the history of metformin use; its pharmacology, mechanism of action, and potential toxicities; and policy-level changes in its use over time. Continue reading >>

More in diabetes