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Metformin And Kidneys Side Effects

Metformin: Side-effects & Benefits

Metformin: Side-effects & Benefits

Editor’s Note: Metformin is considered one of the safest and most effective treatments for type 2 diabetes. Although you should be aware of the side effects below, metformin is typically safe and well-tolerated. Metformin is used alone or with other medications, including insulin, to treat type 2 diabetes (condition in which the body does not use insulin normally and, therefore, cannot control the amount of sugar in the blood). Metformin is in a class of drugs called biguanides. Metformin helps to control the amount of glucose (sugar) in your blood. It decreases the amount of glucose you absorb from your food and the amount of glucose made by your liver. Metformin also increases your body’s response to insulin, a natural substance that controls the amount of glucose in the blood. I’m also beginning to see where metformin is used in addition to insulin to treat type 1 diabetes (condition in which the body does not produce insulin and therefore cannot control the amount of sugar in the blood). How about the associated long term side effects of metformin? Lets take a closer look! *Be sure to read this article: Patients Share their Experience on Metformin. Metformin and Lactic Acidosis: Although rare, lactic acidosis is potentially the most serious of the metformin side effects. The uptake of lactate by the liver is effected by metformin in a negative way. If the kidneys do not process the excess lactate the blood of the patient will acidify which can lead to a whole slew of problems. Most of which are similar to the feeling one gets after an intense workout. For example: anxiety, hyperventilation, irregular heart rate nausea and in some cases vomiting. This is the reason that metformin is generally only prescribed to people with a healthy kidney function. This side e Continue reading >>

Metformin In Chronic Kidney Disease: Time For A Rethink

Metformin In Chronic Kidney Disease: Time For A Rethink

Go to: The Case Against Metformin The main problem with metformin is its association with LA. Lactic acidosis is defined as an arterial lactate of > 5 mmol/L and a blood pH ≤ 7.35 (1,2). There are two forms of LA. Type A is anaerobic LA caused by lactate overproduction in order to regenerate adenosine triphosphate (ATP) in the absence of oxygen, and is usually seen in the presence of circulatory collapse, e.g. heart failure, sepsis, and shock. Type B, the aerobic version, is caused by underutilization of lactate due to impaired removal by oxidation or gluconeogenesis, and is the type seen in liver disease, diabetes, cancer, and alcohol and metformin intoxication. Combinations of Type A & B are possible. The therapeutic trough level for metformin is 0.7 (0.3-1.0) mg/L (3) (for μmol/L, multiply by 7.75). The pragmatic upper therapeutic limit is 5 mg/L (4). There is no doubt that metformin in toxic doses is a cause of LA. In rats, plasma lactate begins to rise if the metformin concentration is > 20 mg/L (5). Intentional metformin overdose usually leads to hyperlactemia (6), and often to LA. This can be fatal in cases with plasma metformin > 50 mg/L (7). Some cases are accompanied by a raised creatinine. Since the most common symptom of metformin intoxication is vomiting and diarrhea, it is possible that the reduced renal function is caused by prerenal dehydration and/or circulatory collapse. Metformin is renally excreted (8,9), with a clearance approximately linearly correlated to glomerular filtration rate (GFR). There are thus two situations where metformin intoxication can occur: failure to reduce the dose in the presence of CKD, and acute uremia. It is possible that a vicious cycle can develop with acute uremia causing metformin accumulation leading to vomiting, deh Continue reading >>

Kombiglyze Xr (metformin,saxagliptin) Dosage, Indication, Interactions, Side Effects | Empr - Renal And Urology News

Kombiglyze Xr (metformin,saxagliptin) Dosage, Indication, Interactions, Side Effects | Empr - Renal And Urology News

Adjunct to diet and exercise in type 2 diabetes when treatment with both saxagliptin and metformin is appropriate. Not for treatment of type 1 diabetes or diabetic ketoacidosis. Individualize; titrate based on response. Swallow whole. Take once daily with evening meal. Not currently treated with metformin: initially 5mg/500mg daily. Previously on metformin alone: Kombiglyze XR dose should provide current metformin dose. Max saxagliptin 5mg/day and metformin ext-rel 2000mg/day. Renal impairment (eGFR 3045mL/min/1.73m2): not recommended; (eGFR <45mL/min/1.73m2): max saxagliptin 2.5mg/day. Concomitant strong CYP3A4/5 inhibitors: max 2.5mg/1000mg daily. Severe renal impairment (eGFR <30mL/min/1.73m2). Metabolic acidosis, diabetic ketoacidosis. Increased risk of metformin-associated lactic acidosis in renal or hepatic impairment, concomitant use of certain drugs (eg, cationic drugs), 65yrs of age, undergoing radiological contrast study, surgery and other procedures, hypoxic states, and excessive alcohol intake; discontinue if lactic acidosis occurs. Discontinue at time of, or prior to intravascular iodinated contrast imaging in patients with eGFR 3060mL/min/1.73m2, history of hepatic impairment, alcoholism, heart failure, or will be given intra-arterial contrast; reevaluate eGFR 48hrs after procedure and restart therapy if renally stable. Suspend therapy if dehydration occurs or before surgery. Avoid if clinical or lab evidence of hepatic disease. Assess renal function prior to starting and periodically thereafter; more frequently in elderly or if eGFR <60mL/min/1.73m2. Consider risks/benefits in patients with known risk factors for heart failure; monitor for signs/symptoms and consider discontinuing if develops. Discontinue if pancreatitis, serious hypersensitivity reactio 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 >>

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 In Patients With Type 2 Diabetes And Kidney Disease

Metformin In Patients With Type 2 Diabetes And Kidney Disease

Go to: Abstract 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. To assess the risk of lactic acidosis associated with metformin use in individuals with impaired kidney function. 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. 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 function. Population-based studies d Continue reading >>

Could Metformin Actually Protect The Kidneys?

Could Metformin Actually Protect The Kidneys?

The drug metformin is not recommended for people with kidney disease. For this reason, some people think that metformin causes kidney disease. But new evidence suggests that metformin might actually protect the kidneys. For many people with type 2 diabetes, metformin is a very effective drug. In everyone, the liver is a sort of “mother” organ. When blood glucose (BG) levels go down, the liver releases some glucose into the blood to make sure all the other organs get enough glucose energy to work properly. When you eat and your BG levels start going up, the liver is supposed to stop pushing all this glucose out into the bloodstream. But for some reason, in people with type 2 diabetes, like an oversolitous mother, the liver doesn’t stop feeding the bloodstream after meals. “Eat eat” I can hear it say to a bloodstream already stuffed with glucose. And this continued release of glucose into the bloodstream after meals is one reason people with type 2 go high after meals. Metformin helps to stop this process, and this is its main action. But it also reduces insulin resistance. In addition, generic metformin is pretty cheap. So overall, it’s a good drug for type 2s or even for type 1s who have developed insulin resistance. Metformin can also cause side effects, especially gastrointestinal distress. Most people find that these side effects are reduced if they start with a low dose and work up to an effective dose. Taking the drug with meals also helps. Others have found that things like yogurt and milk thistle help with the GI symptoms. The extended-release form seems to cause fewer of these problems. But for those with kidney disease, metformin is not so great. This is because metformin is excreted through the kidneys. If the kidneys aren’t functioning well, the 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 >>

Diabetes Drug Could Be Dangerous: Study

Diabetes Drug Could Be Dangerous: Study

A number of patients with diabetes are being given a drug that could kill them, according to researchers in North Carolina. A study on metformin, also sold as Glucophage and Novo-Metformin, says nearly one in four patients could experience dangerous side effects. The study is published in the most current issue of the Journal of the American Medical Association. Metformin helps the body use insulin and is one of the most common drugs used to treat Type II diabetes, sometimes linked to obesity and called "adult-onset" or "non-insulin dependent" diabetes. There are at least 1.2 million Canadians with diabetes according to Health Canada. More than 90 per cent are Type II. Metformin can cause a side-effect called lactic acidosis, a buildup of lactic acid in the blood that is fatal in half of all cases. The label says it shouldn't be used by patients with kidney disease or by those taking heart medication. A study of metformin patients by the University of North Carolina in Chapel Hill found a quarter met that criteria. Fortunately, none of the patients developed lactic acidosis. "It is difficult to determine whether clinicians are aware they are prescribing metformin against a black-box warning," wrote the researchers. "Black-box" refers to the highlighted cautionary information on labels of drugs that have serious side effects. The Canadian Medical Association's guide to prescription drugs lists special precautions for metformin. Metformin is not recommended if you: have impaired kidney or liver function have heart failure are a heavy drinker are pregnant are breast-feeding are over 60 Common reactions are loss of appetite, nausea and vomiting and a metallic taste in the mouth. Lead researcher Cheryl Horlen says several recent European studies have found similar rates of i Continue reading >>

Metformin (glucophage) Side Effects & Complications

Metformin (glucophage) Side Effects & Complications

The fascinating compound called metformin was discovered nearly a century ago. Scientists realized that it could lower blood sugar in an animal model (rabbits) as early as 1929, but it wasn’t until the late 1950s that a French researcher came up with the name Glucophage (roughly translated as glucose eater). The FDA gave metformin (Glucophage) the green light for the treatment of type 2 diabetes in 1994, 36 years after it had been approved for this use in Britain. Uses of Generic Metformin: Glucophage lost its patent protection in the U.S. in 2002 and now most prescriptions are filled with generic metformin. This drug is recognized as a first line treatment to control blood sugar by improving the cells’ response to insulin and reducing the amount of sugar that the liver makes. Unlike some other oral diabetes drugs, it doesn’t lead to weight gain and may even help people get their weight under control. Starting early in 2000, sales of metformin (Glucophage) were challenged by a new class of diabetes drugs. First Avandia and then Actos challenged metformin for leadership in diabetes treatment. Avandia later lost its luster because it was linked to heart attacks and strokes. Sales of this drug are now miniscule because of tight FDA regulations. Actos is coming under increasing scrutiny as well. The drug has been banned in France and Germany because of a link to bladder cancer. The FDA has also required Actos to carry its strictest black box warning about an increased risk of congestive heart failure brought on by the drug. Newer diabetes drugs like liraglutide (Victoza), saxagliptin (Onglyza) and sitagliptin (Januvia) have become very successful. But metformin remains a mainstay of diabetes treatment. It is prescribed on its own or sometimes combined with the newer d 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 >>

Fda Drug Safety Communication: Fda Revises Warnings Regarding Use Of The Diabetes Medicine Metformin In Certain Patients With Reduced Kidney Function

Fda Drug Safety Communication: Fda Revises Warnings Regarding Use Of The Diabetes Medicine Metformin In Certain Patients With Reduced Kidney Function

[ 4-8-2016 ] The U.S. 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. We were asked1,2 to review numerous medical studies regarding the safety of metformin use in patients with mild to moderate impairment in kidney function,3-14 and to change the measure of kidney function in the metformin drug labeling that is used to determine whether a patient can receive metformin. We have concluded our review, and are requiring changes to the labeling of all metformin-containing medicines to reflect this new information. Health care professionals should follow the latest recommendations when prescribing metformin-containing medicines to patients with impaired kidney function. Patients should talk to their health care professionals if they have any questions or concerns about taking metformin. Metformin-containing medicines are available by prescription only and are used along with diet and exercise to lower blood sugar levels in patients with type 2 diabetes. When untreated, type 2 diabetes can lead to serious problems, including blindness, nerve and kidney damage, and heart disease. Metformin-containing medicines are available as single-ingredient products and also in combination with other drugs used to treat diabetes (see FDA Approved metformin-containing Medicines). The current drug labeling strongly recommends against metformin use in some patients whose kidneys do not work normally because use of metformin in these patients can increase the risk of developing a serious and potentially dead Continue reading >>

What Is Metformin's Long-term Effect On Kidney & Liver?

What Is Metformin's Long-term Effect On Kidney & Liver?

Metformin iѕ a prescription drug thаt iѕ uѕеd tо hеlр control blood glucose levels in individuals with type 2 diabetes mellitus. Metformin works bу acting оn thе liver аnd intestines tо decrease secretion аnd absorption оf glucose intо thе blood. It аlѕо increases thе insulin sensitivity оf muscles аnd tissues оf thе bоdу ѕо thаt thеу tаkе uр glucose mоrе readily. Patients taking metformin, раrtiсulаrlу women mау experience general malaise, fatigue, аnd occasional achiness. Malaise mау bе caused bу оthеr effects оf metformin оn thе liver, kidneys, stomach аnd intestines. Research studies around the world have shown that making small changes in lifestyle can reduce the risk of diabetes for people who are overweight and have diabetes. I was searching online and came upon this website Control Your Blood Sugar Level. It’s really helpful. Continue reading >>

Diabetes Drug Metformin Safe For Patients With Kidney Disease: Review

Diabetes Drug Metformin Safe For Patients With Kidney Disease: Review

TUESDAY, Dec. 23, 2014 (HealthDay News) -- Although metformin, the popular type 2 diabetes medication, is usually not prescribed for people with kidney disease, a new analysis shows the drug may be safer for these patients than once thought. Metformin has been used in the United States for two decades to help lower blood sugar levels among people with type 2 diabetes. The U.S. Food and Drug Administration cautions that people with kidney disease should not take the drug because it could increase their risk for a potentially serious condition called lactic acidosis. This is when lactic acid builds up in the bloodstream after oxygen levels in the body are depleted. After reviewing published research to evaluate the risks associated with metformin among people with mild to moderate kidney disease, a team of researchers led by Dr. Silvio Inzucchi, a professor of medicine at Yale University, found these patients were at no greater risk for lactic acidosis than people who were not taking the drug. "What we found is that there is essentially zero evidence that this is risky," Inzucchi, who is also medical director of the Yale Diabetes Center, said in a university news release. "The drug could be used safely, so long as kidney function is stable and not severely impaired," he said. Despite warnings, many doctors are already prescribing metformin to patients with kidney disease, the study published in the Dec. 24/31 issue of the Journal of the American Medical Association revealed. "Many in the field know that metformin can be used cautiously in patients who have mild to moderate kidney problems," Inzucchi said. "Most specialists do this all the time." Still, the researchers said their findings are significant because many doctors stop prescribing metformin once their patients g 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 >>

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