Does Metformin Damage Your Kidneys

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 >>

Original Research Use Of Metformin And Risk Of Kidney Cancer In Patients With Type 2 Diabetes

Highlights • The reimbursement database of the National Health Insurance of Taiwan was used. • Kidney cancer risk was analyzed in users and non-users of metformin. • Metformin reduces the risk of kidney cancer in a dose–response pattern. • The adjusted hazard ratio (95% confidence interval) was 0.279 (0.254–0.307). • Risk of any cancer was also significantly reduced in metformin users. Abstract The anticancer effect of metformin has been reported in the literature but requires additional confirmation in epidemiologic studies. With respect to kidney cancer scarce data are available. This study investigates whether metformin use in patients with type 2 diabetes mellitus (T2DM) might affect kidney cancer risk. The reimbursement database of the National Health Insurance in Taiwan was used. T2DM patients aged ≥40 years and newly treated with either metformin (n = 171,753, “ever users of metformin”) or other antidiabetic drugs (n = 75,499, “never users of metformin”) within 1998–2002 were followed for at least 6 months for kidney cancer until 31 December 2009. The treatment effect was estimated by Cox regression using propensity score weighting by inverse probability of treatment weighting approach. Hazard ratios were estimated for ever versus never users, and for tertiles of cumulative duration of metformin therapy. During follow-up, 917 ever users and 824 never users developed kidney cancer, with respective incidence of 80.09 and 190.30 per 100,000 person-years. The hazard ratio (95% confidence intervals) for ever versus never users is 0.279 (0.254–0.307); and is 0.598 (0.535–0.668), 0.279 (0.243–0.321) and 0.104 (0.088–0.124), respectively, for the first, second, and third tertile of cumulative duration of <14.5, 14.5–45.8 and >45.8 mont Continue reading >>

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 >>

New Diabetes Drug Possibly Protects The Kidneys

New diabetes drug possibly protects the kidneys A new type of drug for treating type 2 diabetes does not only lower blood sugar levels, but also helps to protect the kidneys. This is the conclusion of a research group headed by clinical pharmacologist Hiddo Lambers Heerspink from the UMCG. The research findings will be published online today in Journal of the America Society of Nephrology (JASN). Patients with type 2 diabetes are prone to high blood sugar levels and have a heightened risk of hypertension, weight gain and kidney damage. As a result, research focuses on designing drugs that will reduce blood sugar levels. Until now, metformin was the drug most commonly prescribed, followed by a sulfonylurea derivative such as glimepiride or gliclazide, which stimulates the pancreas to produce insulin. A new drug has now been developed: canagliflozin. This drug inhibits the sodium-glucose cotransporter 2 (SGLT2) in the kidneys but until now, its effect on kidney function had not been properly investigated. Heerspink compared the effects of these two drugs with each other in terms of weight, blood sugar level and kidney function. He used data from 1,450 type 2 diabetes patients from 19 countries, all of whom were taking metformin, the current standard treatment for type 2 diabetes. Some of them were prescribed glimepiride in addition to metformin, while others were also given canagliflozin 100 mg or canagliflozin 300 mg in addition to metformin. For a period of two years, the weight, blood sugar level and kidney function of these patients was regularly monitored. Heerspink concludes that both drugs have roughly the same effect in terms of reducing the blood sugar level. However, kidney function deteriorates less quickly in patients taking canagliflozin. So canagliflozin ap Continue reading >>

Metformin And Kidneys | Amma-rainichi

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Which Diabetes Drug Is Best For Diabetics With Kidney Disease?

Highlights Sitagliptin is as effective as glipizide at lowering blood sugar levels in patients with type 2 diabetes and chronic kidney disease. Sitagliptin is less likely than glipizide to cause dangerously low blood sugar levels. Patients on sitagliptin tend to lose weight, while those on glipizide gain weight. Some blood-sugar-lowering drugs have caused kidney problems in patients with type 2 diabetes, so physicians are especially cautious when prescribing these agents to diabetics who also have chronic kidney disease (CKD). Previous research indicates that the diabetes drugs sitagliptin and glipizide may not cause considerable kidney damage. New clinical trial results presented during the American Society of Nephrology's Annual Kidney Week compared the two drugs. Sitagliptin and glipizide act on different targets but generate the same result--they boost the effects of insulin, which lowers blood sugar levels. Juan Arjona Ferreira, MD, (MSD Corp.) and his colleagues conducted a 54-week study to compare the efficacy and safety of sitagliptin and glipizide in patients with type 2 diabetes and moderate or severe CKD who were not on dialysis. The researchers randomized 426 patients to receive sitagliptin or glipizide. Among the major findings at the end of the study: Blood glucose levels dropped to a similar extent in patients in both groups. Patients receiving sitagliptin were less likely to experience hypoglycemia--or dangerously low blood sugar levels--than patients receiving glipizide (6.2% vs 17.0%). Patients who took sitagliptin tended to lose a small amount of weight, while most patients who took glipizide experienced a slight weight gain. Study authors for "Efficacy and Safety of Sitagliptin vs. Glipizide in Patients with Type 2 Diabetes and Moderate to Severe Chr Continue reading >>

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 >>

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 >>

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 >>

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 >>

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 >>

Side Effects Of Metformin: What You Should Know

Metformin is a prescription drug used to treat type 2 diabetes. It belongs to a class of medications called biguanides. People with type 2 diabetes have blood sugar (glucose) levels that rise higher than normal. Metformin doesn’t cure diabetes. Instead, it helps lower your blood sugar levels to a safe range. Metformin needs to be taken long-term. This may make you wonder what side effects it can cause. Metformin can cause mild and serious side effects, which are the same in men and women. Here’s what you need to know about these side effects and when you should call your doctor. Find out: Can metformin be used to treat type 1 diabetes? » Metformin causes some common side effects. These can occur when you first start taking metformin, but usually go away over time. Tell your doctor if any of these symptoms are severe or cause a problem for you. The more common side effects of metformin include: heartburn stomach pain nausea or vomiting bloating gas diarrhea constipation weight loss headache unpleasant metallic taste in mouth Lactic acidosis The most serious side effect metformin can cause is lactic acidosis. In fact, metformin has a boxed warning about this risk. A boxed warning is the most severe warning from the Food and Drug Administration (FDA). Lactic acidosis is a rare but serious problem that can occur due to a buildup of metformin in your body. It’s a medical emergency that must be treated right away in the hospital. See Precautions for factors that raise your risk of lactic acidosis. Call your doctor right away if you have any of the following symptoms of lactic acidosis. If you have trouble breathing, call 911 right away or go to the nearest emergency room. extreme tiredness weakness decreased appetite nausea vomiting trouble breathing dizziness lighthea Continue reading >>

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 >>

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 >>

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 >>