What Is Metformin?
MORE Metformin is a prescription drug used primarily in the treatment of Type II diabetes. It can be used on its own or combined with other medications. In the United States, it is sold under the brand names Fortamet, Glucophage, Glumetza and Riomet. "Metformin is very often prescribed as the first step in a diabetic's regime," said Ken Sternfeld, a New York-based pharmacist. How it works "When you're diabetic you lose the ability to use the insulin you need to offset the food," Sternfeld explained. "If you eat a carb or sugar that can't be metabolized or offset by the insulin you produce, your sugar levels will be higher. Metformin and drugs in that category will help your body better metabolize that food so that insulin levels will be able to stay more in line." Metformin aims to decrease glucose production in the liver, consequently lowering the levels of glucose in the bloodstream. It also changes the way that your blood cells react to insulin. "It makes them more sensitive to insulin," said Dr. Stephen Neabore, a primary care doctor at the Barnard Medical Center in Washington, D.C. "It makes the same amount of insulin work better. It transports the insulin to the cells in a more effective way." Metformin may have a preventive health role, as well. New research presented at the American Diabetes Association 2017 Scientific Sessions showed that long-term use of metformin is particularly useful in preventing the onset of type II diabetes in women who have suffered from gestational diabetes. Because metformin changes the way the body uses insulin, it is not used to treat Type I diabetes, a condition in which the body does not produce insulin at all. Metformin & PCOS Metformin is sometimes prescribed to treat polycystic ovarian syndrome (PCOS), according to Neabore. "I Continue reading >>
Cardiovascular Safety Of Non-insulin Pharmacotherapy For Type 2 Diabetes
Abstract Patients with type 2 diabetes mellitus have a twofold increased risk of cardiovascular mortality compared with non-diabetic individuals. There is a growing awareness that glycemic efficacy of anti-diabetic drugs does not necessarily translate to cardiovascular safety. Over the past few years, there has been a number of trials evaluating the cardiovascular effects of anti-diabetic drugs. In this review, we seek to examine the cardiovascular safety of these agents in major published trials. Metformin has with-stood the test of time and remains the initial drug of choice. The sulfonylureas, despite being the oldest oral anti-diabetic drug, has been linked to adverse cardiovascular events and are gradually being out-classed by the various other second-line agents. The glitazones are contraindicated in heart failure. The incretin-based drugs have been at the fore-front of this era of cardiovascular safety trials and their performances have been reassuring, whereas the meglitinides and the alpha-glucosidase inhibitors still lack cardiovascular outcomes data. The sodium glucose cotransporter-2 inhibitors are an exciting new addition that has demonstrated a potential for cardiovascular benefit. Many of the currently available oral anti-diabetic agents have clinically relevant cardiovascular effects. The optimal approach to the reduction of cardiovascular risk in diabetic patients should focus on aggressive management of the standard cardiovascular risk factors rather than purely on intensive glycemic control. Background Cardiovascular disease remains the leading cause of morbidity and mortality in type 2 diabetes mellitus (T2DM). Despite a decline in the rate of cardiovascular mortality over time, men and women with diabetes mellitus remain at twofold increased risk [1 Continue reading >>
- Mortality and Cardiovascular Disease in Type 1 and Type 2 Diabetes
- Postprandial Blood Glucose Is a Stronger Predictor of Cardiovascular Events Than Fasting Blood Glucose in Type 2 Diabetes Mellitus, Particularly in Women: Lessons from the San Luigi Gonzaga Diabetes Study
- FDA OKs Two Medicines for Cardiovascular Disease in Type 2 Diabetes
Metformin Linked To Decreased Mortality In Ckd, Chf, And Liver Disease
Metformin is associated with lower all-cause mortality in patients with moderate chronic kidney disease (CKD), congestive heart failure (CHF) and chronic liver disease (CLD), according to a study published in the February issue of the Annals of Internal Medicine.1 “Although data were limited, we found no evidence to suggest that metformin's benefits do not extend to patients with moderate CKD, CHF, or CLD with impaired hepatic function. Together with reports regarding the safety of metformin with respect to lactic acidosis, our findings support the FDA's recent actions,” wrote first author Matthew Crowley, MD, of Durham Veterans Affairs Medical Center (Durham, NC) and Duke University, and colleagues.2 When metformin was first approved in 1994, it was contraindicated in patients with CKD and CLD, due to concerns over lactic acidosis. Several years later, the US Food and Drug Administration (FDA) also advised against its use in CHF. These warnings were motivated, in part, by concerns for lactic acidosis with use of phenformin, a related drug that was pulled from the market in 1977.1,2 Over the years, the FDA has relaxed some of the restrictions over metformin’s use. In 2006, the agency removed CHF as a contraindication for the drug, though still cautioned about its use in acute or unstable CHD.2 In April 2016, the FDA changed metformin’s boxed warning, expanding its use to patients with mild kidney impairment and some patients with moderate renal impairment.3 Collectively, these changes will likely increase metformin use in patients who would have had contraindications in the past. Effective in more patients? To evaluate whether metformin use improves outcomes in an expanded population of patients, researchers searched Medline from January 1994 to September 2016, Continue reading >>
Metformin Associated With Reduced Mortality In Kidney Disease, Congestive Heart Failure, And Chronic Liver Disease
1. Metformin use is associated with reduced all-cause mortality in patients with chronic kidney disease, congestive heart failure, or chronic liver disease with hepatic impairment. 2. In this systemic review, fewer heart failure readmissions were observed in patients with CKD or CHF that were treated with metformin. Evidence Rating Level: 1 (Excellent) Study Rundown: Metformin is currently the suggested initial treatment for type 2 diabetes mellitus in the United States. In the past, the U.S. Food and Drug Administration (FDA did not recommend metformin for patients with chronic kidney disease (CKD), congestive heart failure (CHF), and/or chronic liver disease (CLD) with hepatic impairment. However, these recommendations were removed in 2006 due to the notion that the precautions were too restrictive. The purpose of this study, therefore, was to promote fully informed prescribing by synthesizing data addressing outcomes of metformin in these populations with historical contraindications. The authors concluded that metformin use in patients with moderate CKD, CHF, or CLD with hepatic impairment is associated with improvements in key clinical outcomes. There were several limitations to this study. First, not all outcomes of potential interest were evaluated. Additionally, strength of evidence was low and studies varied in follow-up duration. Overall, the results of this study support changes in metformin labeling to permit metformin use in additional patients with certain types of CHF, CKD, and CLD with hepatic impairment. Click to read the study, published today in the Annals of Internal Medicine Relevant Reading: Metformin in Chronic Kidney Disease: Time for a Rethink In-Depth [systematic review]: In this systematic review, articles were retrieved from MEDLINE, EMBASE, Continue reading >>
The Pros And Cons Of Metformin For Diabetes
Metformin is #7 on the doctors’ hit parade of top 10 prescription drugs. Each year the number of prescriptions increases substantially. Last year there were 87 million metformin prescriptions dispensed in U.S. pharmacies. That does not count combo products that include metformin in their formulation such as Glucovance, Invokamet, Janumet, Kombiglyze XR, Metaglip and Synjardy, to name just a few. Metformin is clearly the #1 drug for diabetes and because the number of people with diabetes keeps going up, prescriptions for metformin are skyrocketing. That’s why readers of our syndicated newspaper column and visitors to this website are so desperate to learn more about metformin for diabetes. How To Know If Metformin for Diabetes Is Right for You: Here is a typical letter from a reader: Q. I crossed the line a month ago from normal blood sugar to type 2 diabetes and was put on metformin. I hate taking drugs. What can you tell me about metformin? Thank the Old Wives: A. Metformin is one of the oldest and most well-studied diabetes medicines. It probably comes as a shock to most prescribers to learn that their favorite diabetes drug is available thanks to the old wives. Practitioners of folk medicine discovered that French lilac (Galega officinalis) helped control the symptoms of a condition associated with “sweet urine.” An article in the Journal of Clinical Investigation (Oct. 15, 2001) noted: “In medieval times, a prescription of Galega officinalis was said to relieve the intense urination accompanying the disease that came to have the name of diabetes mellitus [now known as type 2 diabetes].” The botanist and physician Nicholas Culpeper detailed the health benefits of French lilac in 1656. He described the ability of the plant to lower blood sugar and control Continue reading >>
Need An Add-on To Metformin? Consider This
Need an Add-on to Metformin? Consider This Clinician Reviews. 2017 February;27(2):20-22 David Wyncott is with the St. Joseph Health System Family Medicine Residency, Mishawaka, Indiana. Corey Lyon is with the University of Colorado Family Medicine Residency, Denver. Anne Mounsey is in the Department of Family Medicine at the University of North Carolina, Chapel Hill. Sulfonylureas have been the preferred add-on therapy to metformin for T2DM, but a study finds that DPP-4s have lower risks for death, CV events, and hypoglycemia. 1. Ou SM, Shih CJ, Chao PW, et al. Effects of clinical outcomes of adding dipeptidyl peptidase-4 inhibitors versus sulfonylureas to metformin therapy in patients with type 2 diabetes mellitus. Ann Intern Med. 2015;163:663-672. 2. Hayward RA, Reaven PD, Wiitala WL, et al. Follow-up of glycemic control and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2015;372:2197-2206. 3. American Diabetes Association. Standards of Medical Care in Diabetes2016. Diabetes Care. 2016;39(suppl 1). 4. Garber AJ, Abrahamson MJ, Barzilay JI, et al. Consensus Statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the Comprehensive Type 2 Diabetes Management Algorithm2016 Executive Summary. Endocr Pract. 2016;22: 84-113. 5. Phung OJ, Scholle JM, Talwar M, et al. Effect of noninsulin antidiabetic drugs added to metformin therapy on glycemic control, weight gain, and hypoglycemia in type 2 diabetes. JAMA. 2010;303:1410-1418. 6. Gallwitz B, Rosenstock J, Rauch T, et al. 2-year efficacy and safety of linagliptin compared with glimepiride in patients with type 2 diabetes inadequately controlled on metformin: a randomised, double-blind, non-inferiority trial. Lancet. 2012;380:475-483. 7. Scirica BM, Bhatt DL, Brau Continue reading >>
Cardiovascular Safety Of Anti-diabetic Drugs
Cardiovascular safety of anti-diabetic drugs Department of Pharmacology and Therapeutics Corresponding author: Tel: + 353 214905448, Email: [email protected] Search for other works by this author on: Department of Pharmacology and Therapeutics Department of Pharmacology and Therapeutics Center for Perinatal Medicine, Department of Obstetrics European Heart Journal - Cardiovascular Pharmacotherapy, Volume 2, Issue 1, 1 January 2016, Pages 3243, R. Kumar, D. M. Kerins, T. Walther; Cardiovascular safety of anti-diabetic drugs, European Heart Journal - Cardiovascular Pharmacotherapy, Volume 2, Issue 1, 1 January 2016, Pages 3243, Cardiovascular disease is the leading cause of morbidity and mortality among patients with diabetes, underscoring the importance of choosing anti-diabetic drugs that do not increase cardiovascular risk but might reduce the risk of cardiovascular events. Most type 2 diabetic patients die from cardiovascular causes despite the beneficial effects of blood pressure (BP) and lipid-lowering medications. The prevalence of patients with cardiovascular disease and diabetes mellitus is growing exponentially. Approximately 40% of patients hospitalized with heart failure and reduced ejection fraction have diabetes mellitus. The recent trials conducted in patients with heart failure who had diabetes showed a different response to standard medication, with these patients being more prone to develop side effects than patients with the same degree of heart failure but without diabetes mellitus. Therefore, careful selection of drug therapy paying particular attention to cardiovascular safety is important in optimizing diabetic therapy. This review discusses the efficacy and safety of the most commonly prescribed anti-diabetic drugs in the context of cardiovascul Continue reading >>
Metformin
Metformin, marketed under the trade name Glucophage among others, is the first-line medication for the treatment of type 2 diabetes,[4][5] particularly in people who are overweight.[6] It is also used in the treatment of polycystic ovary syndrome.[4] Limited evidence suggests metformin may prevent the cardiovascular disease and cancer complications of diabetes.[7][8] It is not associated with weight gain.[8] It is taken by mouth.[4] Metformin is generally well tolerated.[9] Common side effects include diarrhea, nausea and abdominal pain.[4] It has a low risk of causing low blood sugar.[4] High blood lactic acid level is a concern if the medication is prescribed inappropriately and in overly large doses.[10] It should not be used in those with significant liver disease or kidney problems.[4] While no clear harm comes from use during pregnancy, insulin is generally preferred for gestational diabetes.[4][11] Metformin is in the biguanide class.[4] It works by decreasing glucose production by the liver and increasing the insulin sensitivity of body tissues.[4] Metformin was discovered in 1922.[12] French physician Jean Sterne began study in humans in the 1950s.[12] It was introduced as a medication in France in 1957 and the United States in 1995.[4][13] It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system.[14] Metformin is believed to be the most widely used medication for diabetes which is taken by mouth.[12] It is available as a generic medication.[4] The wholesale price in the developed world is between 0.21 and 5.55 USD per month as of 2014.[15] In the United States, it costs 5 to 25 USD per month.[4] Medical uses[edit] Metformin is primarily used for type 2 diabetes, but is increasingly be Continue reading >>
#40 Metformin For Patients With Type 1 Diabetes & May 2017 Update On My T1dmanagement
#40 Metformin For Patients With Type 1 Diabetes & May 2017 Update on My T1DManagement I would expect that the majority of those with diabetes, including type 1 diabetes (T1DM), have at least heard of the medication, metformin. It is primarily used to lower blood glucose (BG) in those with type 2 diabetes (T2DM), but does so by addressing insulin resistance, the primary defect in T2DM. However in recent years, it has been used off-label for persons with insulin resistance that leads to other conditions including pre-diabetes, severe obesity, polycystic ovarian syndrome (PCOS), cancer, and T1DM. Its use in T1DM has been targeted to those with signs of insulin resistance which include hypertension, elevated serum triglycerides (>150 mg/dl), reduced HDL-C (<40 mg/dl in males or <50 mg/dl in females), overweight/obesity or elevated waist-to-height ratio (>0.5) (which includes about 25% of those with T1DM). Although any of these signs can be associated with insulin resistance, the more signs one has, the higher the risk of having insulin resistance. The term double diabetes has been used to describe those with T1DM who are also insulin resistant. Insulin resistance as has been reviewed in detail in my blog post #22 primarily in the context of prediabetes and type 2 diabetes. But you may ask, How does a person with T1DM become insulin resistant? You probably wont hear very many provide an explanation for it, but here is mine. I think it is a combination of a diet high in refined (processed) carbohydrates and sugar with the use of exogenous insulin to cover those carbohydrates. Exogenous insulin is far from physiologic and there are many hours of the day or night where there is insufficient insulin to suppress hepatic (liver) glucose production leading to elevated BG (glucotox Continue reading >>
Actos
Actos (pioglitazone) is an oral Type 2 diabetes drug that lowers blood sugar by decreasing insulin resistance and reducing the amount of glucose made in the liver. This allows the body to better dispose of excess blood sugar. Typically, the dose starts at 15 or 30 mg and is taken once a day, but some people may require a stronger dose. Doctors can increase the strength of the medicine by 15 mg increments to a maximum of 45 mg daily. However, numerous studies and a review by the U.S. Food and Drug Administration (FDA) link higher dosages and prolonged use to an increased risk of bladder cancer and other serious conditions. Actos is not intended to treat Type 1 diabetes or diabetic ketoacidosis. The drug can be used alone or with other Type 2 diabetes medicines such as metformin. There are two additional types of Actos that combine pioglitazone and metformin: Actoplus Met and Actoplus Met XR (extended release). What Does Actos Treat? Actos is approved to treat Type 2 diabetes in adults by improving glycemic (defined as causing glucose – sugar – in the blood) control. The drug comes in a tablet form to be taken by mouth daily and should be used in combination with diet and exercise. People with Type 2 diabetes do not make or use insulin well. Insulin is a hormone produced by the pancreas that regulates the amount of glucose in the blood. It moves blood sugar into cells where it is stored for later use as energy. Type 2 diabetes results in higher than normal levels of glucose because glucose does not enter cells. The body is then unable to use the glucose for energy. Type 2 diabetes is a lifelong (chronic) disease that can develop at any age, including during childhood. However, it mostly occurs in middle-aged and older people. The condition often develops slowly over t Continue reading >>
Clinical Care Crossroads: Navigating The Intersection Of Heart Failure And Diabetes
Nathan DM. Diabetes: advances in diagnosis and treatment. JAMA. 2015;314:1052-1062. Abstract Maps of diagnosed diabetes and obesity in 1994, 2000, and 2015. CDC's Division of Diabetes Translation. April 2017. Accessed October 2, 2017. Newman JD, Schwartzbard AZ, Weintraub HS, et al. Primary prevention of cardiovascular disease in diabetes mellitus. J Am Coll Cardiol. 2017;70:883-893. Abstract Rawshani A, Rawshani A, Franzn S, et al. Mortality and cardiovascular disease in type 1 and type 2 diabetes. N Engl J Med. 2017;376:1407-1418. Abstract Kannel WB, Hjortland M, Castelli WP. Role of diabetes in congestive heart failure: the Framingham study. Am J Cardiol. 1974;34:29-34. Abstract Nichols GA, Hillier TA, Erbey JR, et al. Congestive heart failure in type 2 diabetes: prevalence, incidence, and risk factors. Diabetes Care. 2001;24:1614-1619. Abstract Matsushita K, Blecker S, Pazin-Filho A, et al. The association of hemoglobin a1c with incident heart failure among people without diabetes: the atherosclerosis risk in communities study. Diabetes. 2010;59:2020-2026. Abstract Chaudhry SI, Wang Y, Gill TM, et al. Geriatric conditions and subsequent mortality in older patients with heart failure. J Am Coll Cardiol. 2010;55:309-316. Abstract Adams KF, Jr., Fonarow GC, Emerman CL, et al. Characteristics and outcomes of patients hospitalized for heart failure in the United States: rationale, design, and preliminary observations from the first 100,000 cases in the Acute Decompensated Heart Failure National Registry (ADHERE). Am Heart J. 2005;149:209-216. Abstract Effect of metoprolol CR/XL in chronic heart failure: metoprolol CR/XL randomised intervention trial in congestive heart failure (MERIT-HF). Lancet. 1999;353:2001-2007. Abstract McMurray JJ, Packer M, Desai AS, et al. Basel Continue reading >>
Metformin Fails To Reduce Heart Failure After Heart Attack
Metformin fails to reduce heart failure after heart attack Rigorous clinical trial results refute findings from observational studies Washington (March 31, 2014) -- The use of metformin, a common regulator of blood glucose for diabetics, does not help protect against heart failure in non-diabetic patients who have suffered a heart attack, according to research presented at the American College of Cardiology's 63rd Annual Scientific Session. The GIPS-III trial is the first double-blind, randomized, placebo-controlled study conducted to evaluate whether four months of metformin treatment preserved left ventricular function in non-diabetic patients with acute myocardial infarction. Metformin is commonly used in diabetic patients to control blood glucose levels by reducing the amount of glucose absorbed from food or made by the liver. Several observational studies suggested metformin has cardio-protective effects via mechanisms that are independent of the drug's glucose-lowering effect. Myocardial infarction often inflicts injury to the heart muscle, resulting in reduced left ventricular function and affecting the ability of the heart to pump blood throughout the body. Several studies in animal models of myocardial infarction showed that metformin preserved the ability of the heart to pump blood through the body (in other words, maintaining left ventricular function), leading researchers to speculate that the addition of metformin to the standard of care in heart attack patients could possibly prevent post-infarction heart failure. "This study did not prove the benefits of metformin in acute myocardial infarction and as such will not change clinical practice as we might have thought," said Chris P.H. Lexis, M.D., University Medical Center Groningen in the Netherlands, and Continue reading >>
Metformin May Reduce All-cause Mortality In Patients With Congestive Heart Failure
A systematic review of 17 observational studies found that metformin was associated with a reduction in all-cause mortality in patients with type 2 diabetes and chronic kidney disease, congestive heart failure or chronic liver disease with hepatic impairment. Metformin was also associated with fewer heart failure readmissions in patients with chronic kidney disease or congestive heart failure. Lead researcher Matthew J. Crowley, MD, MHS, of Duke University and the Durham Veterans Affairs Medical Center in North Carolina, and colleagues published their results online Jan. 2 in the Annals of Internal Medicine. The U.S. Department of Veterans Affairs funded the study. When the FDA approved metformin in 1994, the drug became the initial treatment option for many people with type 2 diabetes in the U.S., according to the researchers. However, the FDA required a label warning against using metformin in patients with chronic kidney disease and recommended caution for patients with congestive heart failure and chronic liver disease. The researchers noted that the FDA in 2006 removed congestive heart failure as a contraindication to metformin use, although the agency still cautions against the drug’s use in patients with acute or unstable congestive heart failure. They also noted that the FDA in April 2016 revised its warning regarding metformin use in patients with chronic kidney disease. By switching to a more inclusive criteria based on estimated glomerular filtration rate, an estimated one million additional patients with moderate chronic kidney disease are eligible to receive metformin, although the drug remains contraindicated in patients with severe chronic kidney disease. For this analysis, the researchers searched databases, the ClinicalTrials.gov website and other pub Continue reading >>
Metformin
Metformin may rarely cause a serious, life-threatening condition called lactic acidosis. Tell your doctor if you have kidney disease. Your doctor will probably tell you not to take metformin. Also, tell your doctor if you are over 65 years old and if you have ever had a heart attack; stroke; diabetic ketoacidosis (blood sugar that is high enough to cause severe symptoms and requires emergency medical treatment); a coma; or heart or liver disease. Taking certain other medications with metformin may increase the risk of lactic acidosis. Tell your doctor if you are taking acetazolamide (Diamox), dichlorphenamide (Keveyis), methazolamide, topiramate (Topamax, in Qsymia), or zonisamide (Zonegran). Tell your doctor if you have recently had any of the following conditions, or if you develop them during treatment: serious infection; severe diarrhea, vomiting, or fever; or if you drink much less fluid than usual for any reason. You may have to stop taking metformin until you recover. If you are having surgery, including dental surgery, or any major medical procedure, tell the doctor that you are taking metformin. Also, tell your doctor if you plan to have any x-ray procedure in which dye is injected, especially if you drink or have ever drunk large amounts of alcohol or have or have had liver disease or heart failure. You may need to stop taking metformin before the procedure and wait 48 hours to restart treatment. Your doctor will tell you exactly when you should stop taking metformin and when you should start taking it again. If you experience any of the following symptoms, stop taking metformin and call your doctor immediately: extreme tiredness, weakness, or discomfort; nausea; vomiting; stomach pain; decreased appetite; deep and rapid breathing or shortness of breath; dizzi Continue reading >>
Antihyperglycemic Agents And Heart Failure (hf): An Examination Of Recent Studies
In the last 10 years, the study of medications for type 2 diabetes (T2D) has rapidly expanded its investigational footprint to evaluate cardiovascular (CV) effects, a shift driven largely by regulatory guidance that requires at least a demonstration of CV safety. Clinical investigators are also concerned with the effect diabetes medications have on atherosclerotic vascular outcomes as well as HF. Working with Covances Dr. Jonathan Plehn in the webinar The Diabetic Heart: A Focus On Heart Failure , I recently provided a high-level overview of the clinical outcomes data examining the effect of antihyperglycemic therapies on heart failure (HF). Only a handful of trials1 have analyzed more versus less-intensive glycemic control with regards to the effects on HF. In the ACCORD trial, there was a trend for increased risk with more intense glucose control (OR 1.23, 95% CI 0.97-1.57). In contrast, the UKPDS, ADVANCE and VADT trials suggested a favorable effect, although these results were not clinically relevant nor statistically significant. Meta-analysis of the totality of these data suggests there is essentially no effect, either positive or negative, on HF events with glycometabolic modulation using the older therapies available for T2D. Below, I review specific therapies in more detail. Metformin appears to be quite safe in patients with HF, and possibly even beneficial. For example, epidemiologic observational data in a Medicare population discharged from hospital on metformin with a primary diagnosis of HF were associated with a 14% lower relative risk over one year compared with patients prescribed non-insulin sensitizers2. As a result, in the US, its boxed warning about a greater risk of lactic acidosis was removed under the direction of the FDA in 20062. Thiazolidine Continue reading >>
