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Metformin And Reduced Kidney Function

Fda Revises Warnings For Use Of Metformin In Patients With Reduced Kidney Function

Fda Revises Warnings For Use Of Metformin In Patients With Reduced Kidney Function

The Food and Drug Administration (FDA) is requiring labeling changes regarding the recommendations for metformin-containing medicines for diabetes to expand metformin’s use in certain patients with reduced kidney function. The current labeling strongly recommends against use of metformin in some patients whose kidneys do not work normally. The FDA has concluded from the review of studies published in the medical literature that metformin can be used safely in patients with mild impairment in kidney function and in some patients with moderate impairment in kidney function. The FDA is requiring changes to the metformin labeling to reflect this new information and provide specific recommendations on the drug’s use in patients with mild to moderate kidney impairment. The FDA is also recommending that the measure of kidney function used to determine whether a patient can receive metformin be changed from one based on a single laboratory parameter (blood creatinine concentration) to one that provides a better estimate of kidney function in patients with kidney disease (i.e., glomerular filtration rate estimating equation [eGFR]). Continue reading >>

Glycaemic Control After Metformin Discontinuation In Diabetic Patients With A Declining Renal Function

Glycaemic Control After Metformin Discontinuation In Diabetic Patients With A Declining Renal Function

Copyright © 2017 Theresa Leyco 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. Metformin is contraindicated in diabetic patients with declining renal function. This study examined the glycaemic control in diabetic patients with chronic kidney disease when metformin was discontinued. This was a retrospective study. We screened 2032 diabetic patients who attended the Diabetes Clinic at a tertiary hospital between 1 September 2014 and 30 September 2015. We analyzed the data on 69 patients whom metformin was discontinued due to declining renal function and had a complete 6-month follow-up. There was no significant difference in the HbA1c and body weight at 6-month follow-up compared to baseline after metformin discontinuation. The eGFR was significantly lower at 6-month follow-up compared to baseline. Upon metformin discontinuation, the majority of patients had their diabetes medication uptitrated (in particular insulin or sulphonylurea). Patients with an improved glycaemia at 6-month follow-up had further declined in eGFR compared to patients with worsened glycaemia. 17% of the study patients experienced hypoglycaemia. Upon metformin discontinuation, glycaemic control could be optimised with uptitration but should be balanced against the risk of hypoglycaemia. Further improvement in the glycaemic control might indicate further deterioration in the renal function. 1. Introduction The rising prevalence of type 2 diabetes mellitus (T2DM) is considered one of the most challenging public health problems. More than 400 million people will be affected by T2DM by the year 2030, with the greatest increase expe Continue reading >>

Metformin Use In Renal Impairment Extended

Metformin Use In Renal Impairment Extended

For patients with a creatinine clearance of 45–59ml/min or an eGFR of 45–59ml/min/1.73m2, the initial dose of metformin is 500mg or 850mg once daily in the morning with food. The maximum daily dose is 1g in two divided doses with monitoring of renal function every 3–6 months. This change to the prescribing information reflects the advice given in the NICE clinical guideline on the management of type II diabetes, namely that metformin can be used with caution in patients with renal impairment but the dose should be reviewed if the patient's eGFR drops below 45ml/min/1.73m2 and treatment discontinued if the eGFR drops below 30ml/min/1.73m2. The metformin drug entry in MIMS has been updated to reflect the current Glucophage SPCs. The MIMS drug listings for products containing metformin in combination with other drugs (eg, dipeptidyl peptidase 4 inhibitors, SGLT2 inhibitors, pioglitazone) will be updated when the updated SPCs become available. Prescribers should refer to the product SPCs to check if a combination product is suitable for an individual patient with renal impairment. Follow MIMS on Twitter Continue reading >>

You Can Use Metformin Even With Reduced Kidney Function

You Can Use Metformin Even With Reduced Kidney Function

Metformin and 18 brand-name drugs that include it are safe for millions of people with diabetes who have reduced kidney function. This month, the U.S. Food and Drug Administration issued a drug safety communication that will let at least 2.5 million more Americans who have this disease use this diabetes drug. In addition to metformin itself, which is a generic drug, it remains available as Glucophage, the original brand name. Other brands of metformin that the FDA’s decision affects include Actoplus Met, Avandamet, Glucovance, and Janumet. The FDA concluded that “metformin can be used safely in patients with mild impairment in kidney function and in some patients with moderate impairment in kidney function.” When you have impaired kidney function or kidney disease, your creatinine level will be too high. Until now, the prescribing information for drugs containing metformin stated that people with moderately high levels of creatinine in their blood should not take it. For women this level was 1.4 mg/dL and for men 1.5 mg/dL. Now, the FDA says in addition to creatinine, your doctor also needs to consider another measure of kidney function. This is the glomerular filtration rate estimating equation, or eGFR. People shouldn’t start taking metformin if it is below 30 mL/minute/1.73 m2. The FDA also doesn’t recommend that you take metformin when your eGFR is between 30-45 mL/minute/1.73 m2. The myth of lactic acidosis The restriction of metformin’s use among people with kidney problems was based on “a serious and potentially deadly condition called lactic acidosis, in which too much lactic acid builds up in the blood.” But recent studies show that this fear of lactic acidosis is a myth. The most influential of these studies is a Cochrane meta-analysis of data Continue reading >>

Fda On Metformin: Ok In Some Patients With Reduced Kidney Function

Fda On Metformin: Ok In Some Patients With Reduced Kidney Function

The US Food and Drug Administration (FDA) released a Drug Safety Communication in April revising warnings regarding the use of metformin in certain patients with diabetes and reduced kidney function. It is requiring a labeling change by manufacturers of all metformin and metformin-containing drugs. Current labeling, in place since the approval of metformin in 1985, strongly recommends against use of metformin in patients with renal disease or renal dysfunction (eg, SCr levels ≥1.5 mg/dL [men], ≥1.4 mg/dL [women] or abnormal creatinine clearance. FDA also is requiring that labeling recommend use of eGFR rather than SCr to evaluate renal function. The systematic review behind the FDA action was published in the Journal of the American Medical Assocation. The 7 slides above provide a quick clinical update on the FDA guidance. Continue reading >>

Metformin - Renal Impairment And Risk Of Lactic Acidosis

Metformin - Renal Impairment And Risk Of Lactic Acidosis

Publications Key Messages Metformin is generally considered to be first line treatment for type 2 diabetes mellitus. The most important adverse effect is lactic acidosis due to the high fatality rate. Renal impairment is a risk factor for the development of lactic acidosis in patients taking metformin. Metformin can still be used in patients with stable renal impairment but the dose MUST be reduced. Patients should be advised to seek medical attention if they experience symptoms of lactic acidosis or acute kidney injury. Metformin is recommended as the first line oral hypoglycaemia medicine for patients with type 2 diabetes in international guidelines1. However, use has been restricted in patients with renal impairment due to the increased risk of lactic acidosis. The New Zealand metformin data sheets have recently been updated to allow for the use of metformin in patients with stable renal impairment. The contraindication cut-off level for creatinine clearance has changed from <60 mL/min to <15 mL/min. Patients with renal impairment MUST take a lower dose of metformin to avoid toxic concentrations. The maximum daily dose to be used in renal impairment is specified in the metformin data sheet, according to degree of impairment. The metformin data sheets can be found on the Medsafe website (www.medsafe.govt.nz/Medicines/infoSearch.asp). Lactic acidosis Lactate is produced by most tissues and is rapidly cleared by the liver. Levels of lactate increase as a consequence of intracellular acidosis and help to slow down the onset of acidosis. High lactate levels are generally considered to be those above 4 mmol/L2. Lactic acidosis is a condition of high lactate and a pH below 7.352. There are many causes of elevated lactate including2: sepsis and septic shock regional tissue i Continue reading >>

Metformin In Patients With Type 2 Diabetes And Kidney Diseasea Systematic Review

Metformin In Patients With Type 2 Diabetes And Kidney Diseasea Systematic Review

Importance Metformin is widely viewed as the best initial pharmacological option to lower glucose concentrations in patients with type 2 diabetes mellitus. However, the drug is contraindicated in many individuals with impaired kidney function because of concerns of lactic acidosis. Objective To assess the risk of lactic acidosis associated with metformin use in individuals with impaired kidney function. Evidence Acquisition In July 2014, we searched the MEDLINE and Cochrane databases for English-language articles pertaining to metformin, kidney disease, and lactic acidosis in humans between 1950 and June 2014. We excluded reviews, letters, editorials, case reports, small case series, and manuscripts that did not directly pertain to the topic area or that met other exclusion criteria. Of an original 818 articles, 65 were included in this review, including pharmacokinetic/metabolic studies, large case series, retrospective studies, meta-analyses, and a clinical trial. Results Although metformin is renally cleared, drug levels generally remain within the therapeutic range and lactate concentrations are not substantially increased when used in patients with mild to moderate chronic kidney disease (estimated glomerular filtration rates, 30-60 mL/min per 1.73 m2). The overall incidence of lactic acidosis in metformin users varies across studies from approximately 3 per 100 000 person-years to 10 per 100 000 person-years and is generally indistinguishable from the background rate in the overall population with diabetes. Data suggesting an increased risk of lactic acidosis in metformin-treated patients with chronic kidney disease are limited, and no randomized controlled trials have been conducted to test the safety of metformin in patients with significantly impaired kidney fu Continue reading >>

Metformin In People With Kidney Disease

Metformin In People With Kidney Disease

Just over one year ago here at Diabetes Flashpoints, we discussed the possibility that hundreds of thousands of people with both diabetes and kidney disease might benefit from taking the diabetes drug metformin. As we noted then, this drug has carried a “black box” warning on its label — mandated by the U.S. Food and Drug Administration (FDA) — ever since it became available in the United States in 1994, due to concerns about lactic acidosis. This rare but extremely serious reaction was found to be an unacceptably common side effect of a drug related to metformin — phenformin — which was pulled from the U.S. market in 1977. Lactic acidosis is much more common in people with impaired kidney function. Since metformin’s warning label is based, in part, on concerns about a different drug entirely, many researchers have tried to estimate how safe metformin is for people with diabetes whose kidney function is impaired. Last year, we noted that many researchers believe metformin is safe for people with mild to moderate kidney disease, defined as having an estimated glomerular filtration rate (eGFR) of 30–60 ml/min. And one study found that using a safety cutoff of an eGFR of 30 ml/min, nearly one million people in the United States who currently don’t take metformin because of the FDA’s labeling might be able to safely do so. So what’s changed in the last year? The evidence, it seems, has only grown stronger in favor of metformin being more widely prescribed to people with kidney disease. As noted in a recent article at DiabetesInControl.com, the blood-glucose-lowering benefits of loosening restrictions on metformin could be enormous. One study cited in the article, published last August in the journal Diabetes Care, found that depending on how eGFR is ca Continue reading >>

Renal Side Effects Of Metformin

Renal Side Effects Of Metformin

Metformin, or Glucophage, is a drug commonly used to treat type 2 diabetes mellitus. It is available in both short and long-acting forms. RxList reports the most common side effects associated with metformin, occurring in more than 5 percent of patients using the drug, are diarrhea, nausea, vomiting, flatulence, diffuse lack of strength, headache, indigestion and abdominal discomfort. Metformin-induced renal side effects are rare but can be lethal. Video of the Day Metformin is excreted out of the body by the kidneys. When the kidneys are not functioning properly, metformin can accumulate in high concentrations which may result in lactic acidosis. Lactic acidosis is a rare, serious metabolic abnormality that occurs with uncontrolled diabetes, severe hypotension as well as high metformin levels. According to Drugs.com, metformin-induced lactic acidosis is fatal in more than 50 percent of cases and usually occurs in diabetic patients with significant kidney dysfunction. Metformin should be used with great caution in patients with chronic renal disease and should be temporarily discontinued for surgery or procedures requiring radiocontrast agents. Symptoms of lactic acidosis are usually nonspecific but may include hypothermia, hypotension and a slow heart rhythm. Lactic acidosis always mandates immediate hospitalization with intensive supportive care and usually hemodialysis. Acute Renal Failure Acute renal failure is characterized by the kidneys' inability to filter toxins out of the blood as a result of injury to the kidney. There are numerous causes of acute renal failure but one of the more common is dehydration. Gastrointestinal side effects are common with metformin therapy and significant diarrhea or vomiting, particularly when there is underlying chronic renal dise Continue reading >>

Using Metformin In The Presence Of Renal Disease

Using Metformin In The Presence Of Renal Disease

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 >>

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 Safe With Reduced Kidney Function

Metformin Safe With Reduced Kidney Function

This month, the U.S. Food and Drug Administration issued a drug safety communication that allows the nearly 2.5 million Americans who have diabetes with reduced kidney function to use metformin. In addition to metformin itself, which is a generic drug, it remains available as Glucophage, the original brand name. Other brands of metformin that the FDA’s decision affects include Actoplus Met, Avandamet, Glucovance, and Janumet. The FDA concluded that “metformin can be used safely in patients with mild impairment in kidney function and in some patients with moderate impairment in kidney function.” When you have impaired kidney function or kidney disease, your creatinine level will be too high. Until now, the prescribing information for drugs containing metformin stated that people with moderately high levels of creatinine in their blood should not take it. For women this level was 1.4 mg/dL and for men 1.5 mg/dL. Now, the FDA says in addition to creatinine, your doctor also needs to consider another measure of kidney function. This is the glomerular filtration rate estimating equation, or eGFR. People shouldn’t start taking metformin if it is below 30 mL/minute/1.73 m2. The FDA also doesn’t recommend that you take metformin when your eGFR is between 30-45 mL/minute/1.73 m2. The myth of lactic acidosis The restriction of metformin’s use among people with kidney problems was based on “a serious and potentially deadly condition called lactic acidosis, in which too much lactic acid builds up in the blood.” But recent studies show that this fear of lactic acidosis is a myth. The most influential of these studies is a Cochrane meta-analysis of data from 347 comparative trials and cohort studies. They didn’t find a single case of lactic acidosis in more than 70, Continue reading >>

Metformin Reduces Mortality In Ckd, Chf, And Cld

Metformin Reduces Mortality In Ckd, Chf, And Cld

FDA label update will increase drug use in persons with historical contraindications or precautions. From 1950 to 1995, we only had 1 class of drugs for type 2 diabetes. Then in 1994, metformin was approved. And it has become the cornerstone therapy for patients with type 2 diabetes. There was and still is a warning of possible lactic acidosis. However, because phenformin was withdrawn due to lactic acidosis in 1977, the FDA put a boxed warning on metformin stating that it should not be used in patients with chronic kidney disease (CKD), to avoid accumulation of the drug, which could possibly lead to lactic acidosis. There was also a warning concerning individuals who may accumulate lactate such as patients with congestive heart failure (CHF) and chronic liver disease (CLD). However, over the years, individuals who had CKD, CHF, or CLD were on metformin. This present study looked at these patients to see if metformin conferred any benefit relative to their chronic diseases. The researchers reviewed five observational studies with a total of 33,442 patients with moderate to severe CKD. In the metformin-treated groups, all-cause mortality was reduced by 33% (HR, 0.77). They looked at 11 observational studies with 35,410 patients with CHF. All-cause mortality was reduced by 22% (HR, 0.78) in the metformin-treated groups. In the three studies on CLD, there was a trend toward benefit with metformin; however, the numbers were small they did not reach statistical significance. This article nicely shows that there was no increased harm in using metformin in patients with CKD, CHF, or CLD; in fact, there was a significant reduction in death in CKD and CHF patients. Therefore, the new FDA label for metformin that was just updated in April 2016 seems to be a step in the right dire Continue reading >>

Can Metformin Cause Kidney Problems?

Can Metformin Cause Kidney Problems?

Actually, metformin is usually not the original cause of kidney problems. However, metformin is eliminated by the kidneys and when a patient has poor kidney function, the metformin can build up in the blood and cause a rare but serious condition called lactic acidosis. Lactic acidosis affects the chemistry balance of your blood and can lead to kidney failure and other organ failure. The risk of lactic acidosis is very low and most often occurs in patients with poor kidney function - so for most patients, the benefits of metformin outweigh the risks of treatment. Most doctors will regularly perform kidney function tests to make sure the kidney is working well in patients who are taking metformin. With that said, if you are taking metformin, contact your doctor immediately if you experience unexplained weakness, muscle pain, difficulty breathing, or increased drowsiness - these can be early signs of lactic acidosis. Also, if you are taking metformin and going to receive a radiocontrast dye study or have surgery, tell your doctors that you are taking metformin - in most cases, your doctor will instruct you to temporarily stop taking metformin during these procedures to help decrease the risk of lactic acidosis. Continue Learning about Metformin Videos Important: This content reflects information from various individuals and organizations and may offer alternative or opposing points of view. It should not be used for medical advice, diagnosis or treatment. As always, you should consult with your healthcare provider about your specific health needs. Continue reading >>

Ema Approval For Metformin In Patients With Renal Impairment

Ema Approval For Metformin In Patients With Renal Impairment

The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion recommending extension of the label for all metformin-containing products to included patients with stable moderate renal failure (chronic kidney disease stage 3). The maximum daily metformin dose will be 2000 mg/day in CKD stage 3a (GFR = 45-59 ml/min) and 1000 mg/day in CKD stage 3b (GFR = 30-44 ml/min), allowing a large additional group of type 2 diabetes patients with reduced kidney function to benefit from the treatment. The product information for these medicines will be updated to revise the current contraindication and give information about doses, monitoring and precautions in patients with reduced kidney function. Following a routine evaluation of the safety of metformin medicines, it was found that based on scientific evidence and clinical guidelines, patients with moderate renal failure may stand to benefit from treatment with metformin, and that the contraindication may therefore no longer be justified. Based on this evidence, the EMA issued an Article 31 referral requesting a cumulative review of the benefit and risk in this patient group across all companies selling metformin companies in the European Union. The EMA reviewed the data submitted by all companies, and as a result, the CHMP has issued a positive opinion on lifting the contraindication for treatment of type 2 diabetes patients with renal impairment CKD stage 3. More information EMA summary on metformin in moderate renal failure Continue reading >>

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