Subgroup Analysis After Psm
When performing a subgroup analysis of the PSM cohort, the metformin group still had a lower risk of all-cause mortality and ESRD progression . Metformin usage showed more risk reduction in obese patients in all-cause mortality and ESRD progression. Patients who used metformin and sulfonylurea at the same time benefited more than those who used metformin alone. In contrast, compared with metformin therapy alone, the simultaneous use of metformin with insulin or RAS blockers had less benefit.
What Is Chronic Kidney Disease
Kidney disease also known as nephropathy is a very common complication of persistently high blood sugar levels in people with diabetes. Approximately 50 percent of all kidney failure cases in the United States are associated with type 2 diabetes.
Diabetes-related kidney disease is defined by damage occurring largely in the blood vessels and nerve-endings in your kidney, impairing its ability to manage and properly filter waste in your bloodstream.
There are 5 stages of kidney disease, the final stage being end-stage renal failure which will lead to death if a patient doesnt receive serious intervention like a transplant or daily dialysis.
Fortunately, diligent blood sugar management can not only prevent CKD but can also prevent it from worsening after it has already developed.
This is where metformin comes in as a potentially doubly impactful treatment option to lower blood sugar levels and protect the kidneys from further damage as seen in this most recent study.
How Is Your Kidney Health
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Glycaemic Control After Metformin Discontinuation In Diabetic Patients With A Declining Renal Function
Chin Meng Khoo
1Department of Medicine, National University Hospital, Singapore
2Yong Loo Lin School of Medicine, National University of Singapore, Singapore
3Higher Education Department, Centre for International Education, Cebu, Philippines
Abstract
1. Introduction
The rising prevalence of type 2 diabetes mellitus 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 expected in Asian populations . Metformin is the recommended first-line antidiabetic therapy for all patients in addition to lifestyle change. Metformin is a very effective antidiabetic agent, widely available and affordable. Its most common side effect is gastrointestinal irritation. T2DM is associated with dismal micro- and macrovascular complications. One of the most dreadful microvascular complications is diabetic nephropathy, which is often characterised by declining estimated glomerular filtration rate and proteinuria. Declining renal function prohibits many medications for fear of potential side effects from lower renal clearance. As such, it is recommended that metformin should be discontinued when the eGFR falls to 30ml/minute/1.73m2 or below , in anticipation of a higher risk of lactic acidosis. Other antidiabetic agents including sulfonylureas, meglitinides, dipeptidyl peptidase-4 inhibitors, and insulin have been shown to be safe in patients with declining renal function .
3. Results
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Inclusion And Exclusion Criteria
Inclusion criteria were: RCT, p-h/sa of RCTs, or OSs provision of endpoints for all-cause mortality and cardiovascular events in patients with T2DM and CKD with or without metformin use. The tested outcomes were assured by physical tests and hospital records, or recognized from links of administrative records. The exclusion criteria were: kidney transplant case report, comment, editorial, letter, quasi-experiment , or unpublished study abstract or conference proceeding. Of two or more articles from the same team or organization, only the one with latest publication or largest sample size was selected.
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Metformin Side Effects On The Heart
Metformin, sold under the brand name Glucophage, is an anti-hyperglycemic medication used alone or in combination with other medication, such as insulin, to control blood glucose levels in those with Type 2 diabetes 1. It belongs in the biguanide class of medication. According to Drugs.com, metformin works by decreasing the amount of glucose obtained from food and glucose produced by the liver, lowering blood glucose levels 12.
If you are experiencing serious medical symptoms, seek emergency treatment immediately.
What Other Injectable Medicines Treat Type 2 Diabetes
Besides insulin, other types of injected medications are offered. These medications assist keep your blood sugar level from going expensive after you consume. They might make you feel less hungry and help you lose some weight. Other injectable medications are not alternatives to insulin.
What should I learn about adverse effects of diabetes medicines?Side effects are issues that arise from a medicine. Some diabetes medications can trigger hypoglycemia, also called low blood glucose, if you dont balance your medications with food and activity.Ask your doctor whether your diabetes medicine can trigger hypoglycemia or other side results, such as indigestion and weight gain. Take your diabetes medications as your healthcare specialist has advised you, to assist prevent side effects and diabetes issues.
You were looking forGlipizide Effects On Kidneys? You probably will discover some useful info in this short article, come have a glance!
Taking insulin or other diabetes medications is often part of treating diabetes Together with healthy food options and physical activity, medication can assist you manage the disease. Some other treatment alternatives are also available.
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Could Metformin Actually Protect The Kidneys
by Patient Expert
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 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.
But a new study suggests that in people with healthy kidneys, metformin could help to preserve their function. It does this by increasing levels of a molecule known as AMPK .
Rosiglitazone also increases adiponectin levels.
Data Isolation And Quality Assessment
Two investigators independently extracted all information of interest in standardized form, including demographic characteristics of patients , stage of CKD, duration of DM, and follow-up duration. Other data of concern included study information , type, intervention, and clinical outcomes , analysis scheme , and effect levels . We acquired effect estimates from models with minimal or full adjustment and reporting the adjusting variables.
The quality of each p-h/sa of RCT or OS was assessed by Y.H. and M.L. with a 9-star NewcastleOttawa scale , and high quality was implied by a score > 6 stars. The evidence quality of each outcome among the enrolled articles was assessed as deficient, low, modest or high by YH and ML independently according to Grading of Recommended Assessment, Development and Evaluation . Any inconsistency between them was addressed via discussion.
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How Metformin Prevents Kidney Disease Progression
For patients at stage 3B or earlier in their kidney disease, metformin showed a dramatic decrease in their risk of progressing to stages 4 and 5, as well as their overall risk of dying.
The study included 10,426 patients from South Korea with both type 2 diabetes and chronic kidney disease. The patients were followed for 7.5 years.
Metformin Causes Scary Lactic Acidosis
The risk of metformin causing lactic acidosis of the blood is exceedingly rare. A Cochrane systematic review of 70,490 patients with type 2 diabetes on metformin did not report a single case of metformin-induced lactic acidosis. The risk of metformin causing lactic acidosis appears to be no greater than that of non-metformin therapies.
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There Is No Epidemiological Evidence That Metformin Use Increases The Risk Of La
A Cochrane analysis of 347 controlled studies covering 70,490 patient-years of metformin use revealed no cases of LA and no significant change in p-lactate . There is no correlation between metformin and lactate controls . In 43% of these studies, CKD was not a contraindication. In a population of T2DM patients with no access to biguanide therapy, the incidence of LA was 9.7-16.9/100,000 patient-years . In all cases, proximal medical causes were identified in the form of hypotension, sepsis, or congestive heart failure, and can thus be classified as Type A LA. Thus, all diabetic patients, regardless of treatment, have an increased risk of LA when faced with circulatory challenge, and the risk of MALA should be compared with this intrinsic risk. The quoted incidence of MALA varies from 0-9.7 and is thus comparable with this figure. Indeed, in two studies where this was investigated, the incidence of sulphonylurea-associated LA was higher than MALA . One might argue that this low incidence was the result of pedantic attention to contraindications in reality, stated contraindications, mainly CKD, are widely ignored in general practice, with a contraindication prevalence varying from 19-94% of treated patients . In one center over 1,000 patients with CKD have been treated without any cases of MALA .
The Bottom Line For Metformin And Kidney Disease
The answer to the question Is metformin bad for the kidneys? is generally no. Metformin can be used in patients with kidney disease. It actually leads to better outcomes in these patients. However, the risk of metformin-induced lactic acidosis increases in CKD stage 4 and above. It is, therefore, not recommended for use in these patients and patients with acute kidney injury. I also recommend avoiding it in patients with renovascular disease because their kidney function tends to fluctuate. Furthermore, metformin can be associated with vitamin B12 deficiency and patients should be screened initially and periodically for deficiency of this important vitamin.
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What Medicines Might I Consider Diabetes
The medication you take will vary by your type of diabetes and how well the medicine controls your blood sugar levels, likewise called blood sugar level. Other factors, such as your other health conditions, medication expenses, and your daily schedule might contribute in exactly what diabetes medication you take.
Metformin And Vitamin B12 Deficiency
The association between long-term use of metformin and low vitamin B12 levels in type 2 diabetes mellitus patients is well-established. This is thought to be due to changes in the production of intrinsic factor in the stomach, which decreases vitamin B12 absorption in the intestine. Vitamin B12 deficiency is more pronounced if the patient is also taking a proton pump inhibitor such as omeprazole or histamine H2 receptor antagonist such as famotidine, which are medications used to treat acid reflux. Since diabetes can cause peripheral neuropathy, as well as vitamin B12 deficiency can cause peripheral neuropathy, it can be confusing for diabetic patients on metformin and their practitioners.
Therefore, patients using metformin for a prolonged period should be screened initially and periodically for vitamin B12 deficiency. In addition, there is also growing evidence that other B vitamins, vitamin D, and magnesium can be impacted by metformin.
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Metformin And Chronic Kidney Disease
Systematic review evaluates benefits and harms of metformin use in people with diabetes and CKD.
Blake Cameron, MD, discusses his teams research on clinical outcomes of metformin use in people with chronic kidney disease and explains what health care professionals need to know about changes to the U.S. Food and Drug Administrations guidance on metformin. These changes make some people who have both diabetes and CKD eligible to take metformin, and research suggests that the medication may have benefits for this population.
Q: Why did the U.S. Food and Drug Administration add a boxed warning about metformin use in people with CKD when it approved the medication in 1994?
A: The story on metformin is really a story of guilt by association. Metformin belongs to a class of drugs called biguanides. From the 1950s to the 1970s, the leading drug in the biguanide class was phenformin. Globally, metformin was rarely used because phenformin was much more effective in lowering blood sugar. However, phenformin had a big problem: it was killing people. In 1977, phenformin was pulled from the U.S. market because it caused a fatal condition called lactic acidosis.
Q: How has the FDA changed the boxed warning about metformin use in people with CKD?
The FDAs new boxed warning indicates that metformin can be initiated in patients who have an eGFR greater than 45 mL/min, and treatment can be continued in existing patients as long as the eGFR remains above 30 mL/min.
The Miracle Of Metformin Against Cancer:
Before you give up on metformin because of side effects and scary stories, we want to tell you about some surprising benefits of this drug. There is growing evidence that it may have impressive anti-cancer activity. In particular, there are data suggesting that metformin may lower the risk of developing breast cancer, liver cancer, pancreatic cancer and colorectal cancer in people with diabetes and that the overall risk of developing cancer in such patients is substantially lower. Not only does the drug seem to reduce the risk of developing a number of common cancers but it might reduce the spread of cancer once it is diagnosed.
Researchers are beginning to tease out one of the proposed mechanisms for the anti-tumor action of metformin, especially in prostate cancer. One study involving 388,760 men who participated in national health screening program in Korea during 2002-2003 were observed from 2004 to 2013 . They looked at aspirin, statins, and metformin use on prostate cancer incidence and mortality.
Statins had no noticeable impact on prostate cancer. The authors offered this result:
In conclusion, metformin use was associated with lower PC incidence. Use of aspirin and that of metformin among diabetic patients were associated with lower PC mortality.
A study in the journal Prostate Cancer and Prostatic Diseases reported that effective treatment for aggressive or advanced disease is challenging.
The researchers note:
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Current Guidelines And Future Implications
These studies highlight the lack of randomised clinical trials to test the specific hypothesis that metformin is safe in patients with mild to moderate CKD. Randomised trials would help to better inform evidence-based guidelines. Nevertheless, given the rarity of LA in the setting of metformin therapy, a study would need to examine hundreds of thousands of patients for many years to demonstrate noninferiority compared with other hypoglycaemic agents, which might not be feasible. National patient registries might be a reasonable alternative however, for regulatory bodies at this time, the best available evidence is limited to meta-analyses, retrospective studies, and smaller mechanistic investigations reported herein.
Other non-American guidelines considered the use of eGFR to determine the safety of metformin. The National Institute for Health and Care Excellence recommends using metformin with caution in patients58 for whom serum creatinine > 130 mol/L or eGFR < 45 mL/min. Doses should be lower and prescribed with increased frequency of monitoring. In patients already taking metformin, the drug should be discontinued if the serum creatinine > 150 mol/L or GFR < 30mL/min.
Managing The Side Effects Of Metformin
Most of the common side effects of metformin involve your digestive system. You can minimize your chances of developing side effects by:
- Starting with a low dose. Its best to start at a low dose and work up over time to reduce the chances of developing side effects. A typical starting dose is 500 milligrams.
- Taking metformin with a meal. Taking metformin with a meal can help reduce your chances of developing an upset stomach or gastric discomfort.
- Taking extended-release metformin. You can talk with a doctor to see if extended-release metformin might be right for you. This type of metformin releases slowly over time and typically has milder side effects. Be sure to discuss the FDA recall of certain brands of metformin extended release, to ensure youre getting a safe version.
- Taking pills whole. You shouldnt crush up pills. Doing so can speed up the rate that theyre absorbed.
If you develop uncomfortable side effects, its a good idea to contact your doctor. They may recommend changing the dosage of the type of metformin youre taking. You may find that you need to change your dosage, particularly during periods of stress.
Its also a good idea to avoid drinking heavily when taking metformin because it can increase your chances of developing lactic acidosis.
Several factors raise your risk of lactic acidosis while taking metformin. If any of these factors affect you, be sure to discuss them with your doctor before taking this drug.
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