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Metformin Acute Chf

Wrongfully Accused: Metformin Use In Heart Failure

Wrongfully Accused: Metformin Use In Heart Failure

Expert Rev Cardiovasc Ther.2011;9(2):147-150. Metformin has long been the cornerstone of therapy for glycemic control in patients with Type 2 diabetes worldwide. It is recommended as first-line therapy by all major diabetes clinical practice guidelines owing to its efficacy, favorable tolerability profile and beneficial effects in limiting weight gain. Moreover, metformin is the only oral anthyperglycemic agent shown in randomized controlled trials to reduce mortality in newly diagnosed patients with Type 2 diabetes. However, the use of metformin has not been without controversy, in particular in patients with heart failure. This article will review a recent observational study by Aguilar et al. published in Circulation Heart Failure that reported improved outcomes associated with metformin therapy in patients with diabetes and heart failure. Heart failure is a very common comorbidity present in 2540% of all adults with diabetes.[ 1 ] Diabetes also portends poorer outcomes in patients with heart failure and hyperglycemia is associated with increased risk of hospital admission.[ 2 ] Historically, the use of metformin in patients with comorbid heart failure was considered 'absolutely' contraindicated owing to the perceived increased risk of lactic acidosis. Recently, regulatory bodies in both Canada (Health Canada) and the USA (US FDA) have removed the heart failure contraindication from product labeling for metformin, although a 'black box' warning for the cautious use of metformin in this population still exists. How best to control blood glucose in patients with diabetes and heart failure still remains controversial owing to the lack of randomized controlled trial evidence. Indeed, except for one small randomized controlled trial (n = 222),[ 3 ] patients with heart fa Continue reading >>

Metformin And Heart Failure: Never Say Never Again

Metformin And Heart Failure: Never Say Never Again

Metformin represents the cornerstone of treatment for type 2 diabetes mellitus. Traditionally, heart failure (HF) was considered a contraindication to its use. However, more recent evidence has shown that this should no longer be the case. Indeed, studies have demonstrated that metformin may even reduce the risk of incident HF and mortality in diabetic patients, while improving up to 2-year survival rates in those with HF. In addition, it appears to exert cardioprotective actions. Although longer follow-up data and more explicit information about the situation in patients with very advanced HF are needed, the cardiac safety of metformin has profound clinical implications and may be anticipated to further encourage its widespread use. 1. Introduction Metformin has long been established as the mainstay of treatment for type 2 diabetes mellitus (T2DM) [1,2] Nathan DM, Buse JB, Davidson MB, Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2009;32:193-203 Papanas N, Maltezos E, Mikhailidis DP. Metformin: diamonds are forever. Expert Opin Pharmacother 2009;10:2395-7. Not only does it reduce hyperglycaemia but it is not associated with unwanted hypoglycaemia (unless used along with insulin or excessive exercise), and it has favourable actions on body weight and serum lipids [3]. More importantly, based on an observational study of participants in a large randomised controlled trial (RCT), it confers long-term protection from all T2DM-related endpoints, myocardial infarction and death from any cause [4]. Traditionally, the use of metformin has been subject to contraindications Continue reading >>

Metformin, Heart Failure, And Lactic Acidosis: Is Metformin Absolutely Contraindicated?

Metformin, Heart Failure, And Lactic Acidosis: Is Metformin Absolutely Contraindicated?

Many patients with type 2 diabetes are denied treatment with metformin because of “contraindications” such as cardiac failure, which may not be absolute contraindications Summary points Treatment with metformin is not associated with an increased risk of lactic acidosis among patients with type 2 diabetes mellitus who have no cardiac, renal, or liver failure Despite increasing disregard of contraindications to metformin by physicians, the incidence of lactic acidosis has not increased, so metformin may be safe even in patients with “contraindications” The vast majority of case reports relating metformin to lactic acidosis report at least one other disease/illness that could result in lactic acidosis Use of metformin in patients with heart failure might be associated with lower mortality and morbidity, with no increase in hospital admissions and no documented increased risk of lactic acidosis Further studies are needed to assess the risk of lactic acidosis in patients with type 2 diabetes and traditional contraindications to metformin Metformin first became available in the United Kingdom in 1957 but was first prescribed in the United States only in 1995.w1 The mechanism of action has been extensively reviewed.w2 w3 The UK prospective diabetes study showed that metformin was associated with a lower mortality from cardiovascular disease than sulphonylureas or insulin in obese patients with type 2 diabetes mellitus.1 It was also associated with reduced all cause mortality, which was not seen in patients with equally well controlled blood glucose treated with sulphonylureas or insulin.1 Despite the evidence base for the benefits of metformin, concerns remain about its side effects and especially the perceived risk of lactic acidosis in the presence of renal, hepatic Continue reading >>

Metformin May Reduce All-cause Mortality In Patients With Congestive Heart Failure

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 >>

Prescribing Information & Medication Guides

Prescribing Information & Medication Guides

Prescribing Information & Medication Guides Indication: NESINA (alogliptin), KAZANO (alogliptin and metformin HCl), and OSENI (alogliptin and pioglitazone) are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. NESINA, KAZANO, and OSENI are not for treatment of type 1 diabetes or diabetic ketoacidosis. Please see Important Safety Information , including boxed warnings for Congestive Heart Failure and LacticAcidosis,below. For detailed information on KAZANO, select a linkbelow. Important Safety Information for NESINA, KAZANO, andOSENI WARNING: CONGESTIVE HEART FAILUREforOSENI Thiazolidinediones, including pioglitazone, which is a component of OSENI, cause or exacerbate congestive heart failure in some patients. After initiation of OSENI, and after dose increases, monitor patients carefully for signs and symptoms of heart failure (e.g., excessive, rapid weight gain, dyspnea, and/or edema). If heart failure develops, it should be managed according to current standards of care and discontinuation or dose reduction of pioglitazone in OSENI must be considered. WARNING: CONGESTIVE HEART FAILUREforOSENI Thiazolidinediones, including pioglitazone, which is a component of OSENI, cause or exacerbate congestive heart failure in some patients. After initiation of OSENI, and after dose increases, monitor patients carefully for signs and symptoms of heart failure (e.g., excessive, rapid weight gain, dyspnea, and/or edema). If heart failure develops, it should be managed according to current standards of care and discontinuation or dose reduction of pioglitazone in OSENI must be considered. OSENI is not recommended in patients with symptomatic heart failure. Initiation of OSENI in patients with established New York Heart A Continue reading >>

Diabetes Treatments And Risk Of Heart Failure, Cardiovascular Disease, And All Cause Mortality: Cohort Study In Primary Care

Diabetes Treatments And Risk Of Heart Failure, Cardiovascular Disease, And All Cause Mortality: Cohort Study In Primary Care

Diabetes treatments and risk of heart failure, cardiovascular disease, and all cause mortality: cohort study in primary care Diabetes treatments and risk of heart failure, cardiovascular disease, and all cause mortality: cohort study in primary care BMJ 2016; 354 doi: (Published 13 July 2016) Cite this as: BMJ 2016;354:i3477 Julia Hippisley-Cox, professor of clinical epidemiology and general practice, Carol Coupland, professor of medical statistics in primary care Division of Primary Care, University Park, University of Nottingham, Nottingham NG2 7RD, UK Correspondence to: J Hippisley-Cox Julia.hippisley-cox{at}nottingham.ac.uk ObjectiveTo assess associations between risks of cardiovascular disease, heart failure, and all cause mortality and different diabetes drugs in people with type 2 diabetes, particularly newer agents, including gliptins and thiazolidinediones (glitazones). Setting1243 general practices contributing data to the QResearch database in England. Participants469 688 people with type 2 diabetes aged 25-84 years between 1 April 2007 and 31 January 2015. ExposuresDiabetes drugs (glitazones, gliptins, metformin, sulphonylureas, insulin, other) alone and in combination. Main outcome measureFirst recorded diagnoses of cardiovascular disease, heart failure, and all cause mortality recorded on the patients primary care, mortality, or hospital record. Cox proportional hazards models were used to estimate hazard ratios for diabetes treatments, adjusting for potential confounders. ResultsDuring follow-up, 21 308 patients (4.5%) received prescriptions for glitazones and 32 533 (6.9%) received prescriptions for gliptins. Compared with non-use, gliptins were significantly associated with an 18% decreased risk of all cause mortality, a 14% decreased risk of heart fai Continue reading >>

Metformin Revisited: A Critical Review Of The Benefitrisk Balance In At-risk Patients With Type 2 Diabetes - Em|consulte

Metformin Revisited: A Critical Review Of The Benefitrisk Balance In At-risk Patients With Type 2 Diabetes - Em|consulte

Received:8February2013; accepted:12February2013 Metformin revisited: A critical review of the benefitrisk balance in at-risk patients with type 2 diabetes La metformine revisite: une revue critique de la balance bnfice/risque chez les patients diabtiques de type 2dits risque Division of Diabetes, Nutrition and Metabolic Disorders and Division of Clinical Pharmacology, Department of Medicine, CHU Sart-Tilman (B35), University of Lige, 4000 Lige, Belgium Corresponding author. Tel.: +32 4 3667238; fax: +32 4 3667068. Metformin is unanimously considered a first-line glucose-lowering agent. Theoretically, however, it cannot be prescribed in a large proportion of patients with type 2 diabetes because of numerous contraindications that could lead to an increased risk of lactic acidosis. Various observational data from real-life have shown that many diabetic patients considered to be at risk still receive metformin and often without appropriate dose adjustment, yet apparently with no harm done and particularly no increased risk of lactic acidosis. More interestingly, recent data have suggested that type 2 diabetes patients considered at risk because of the presence of traditional contraindications may still derive benefit from metformin therapy with reductions in morbidity and mortality compared with other glucose-lowering agents, especially sulphonylureas. The present review analyzes the benefitrisk balance of metformin therapy in special populations, namely, patients with stable coronary artery disease, acute coronary syndrome or myocardial infarction, congestive heart failure, renal impairment or chronic kidney disease, hepatic dysfunction and chronic respiratory insufficiency, all conditions that could in theory increase the risk of lactic acidosis. Special attention is al Continue reading >>

Metformin In Diabetic Patients With Heart Failure: Safe And Effective?

Metformin In Diabetic Patients With Heart Failure: Safe And Effective?

Metformin in Diabetic Patients with Heart Failure: Safe and Effective? The University of Texas Medical School at Houston, Division of Cardiovascular Medicine Correspondence to: Heinrich Taegtmeyer, MD, DPhil, 6431 Fannin St, MSB 1.246, Tel: 713-500-6569, Fax: 713-500-0637, [email protected] Ijeoma Ananaba Ekeruo, MD, 6431 Fannin St, MSB 1.246, Tel: 713-500-6569, Fax: 713-500-0637, [email protected] Amirreza Solhpour, MD, 6431 Fannin St, MSB 1.246, Tel: 713-500-6569, Fax: 713-500-0637, [email protected] See other articles in PMC that cite the published article. Management of diabetic patients with heart failure is a complex endeavor. The initial reluctance to use metformin in these patients has given way to a broader acceptance after clinical trials and meta-analyses have revealed that some of the insulin-sensitizing agents lead to adverse cardiovascular events. We have proposed that an increase of substrate uptake by the insulin-resistant heart is detrimental because the heart is already flooded with fuel. In light of this evidence, metformin offers a unique safety profile in the patient with diabetes and heart failure. Our article expands on the use of metformin in patients with heart failure. We propose that the drug targets both the source as well as the destination (in this case the heart) of excess fuel. We consider treatment of diabetic heart failure patients with metformin both safe and effective. Keywords: Type 2 Diabetes Mellitus, Heart Failure, Anti-diabetic Drugs Of the estimated 25.8 million people with the diagnosis of type 2 diabetes in the United States, about 30% will develop heart failure( 1 ), contributing to the exorbitant cost of diabetes. For example, in 2012 alone, the cost of diagnosed diabetes was $245 billion in total Continue reading >>

Metformin Reduces Mortality In Ckd, Chf, And Cld

Metformin Reduces Mortality In Ckd, Chf, And Cld

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

Review Article Metformin In Heart Failure Patients

Review Article Metformin In Heart Failure Patients

Summary The use of metformin was considered a contraindication in heart failure patients because of the potential risk of lactic acidosis; however, more recent evidence has shown that this should no longer be the case. We reviewed the current literature and the recent guideline to correct the misconception. Continue reading >>

Metformin And Heart Failure

Metformin And Heart Failure

Innocent until proven guilty Throughout the world and for many years, metformin has been a mainstay of therapy for patients with type 2 diabetes. This highly effective and usually well-tolerated oral agent is, to date, the only one demonstrated to reduce cardiovascular disease (CVD) complications in newly diagnosed type 2 diabetic patients (1). It's precise mechanism of action remains enigmatic, although it clearly results in a reduction of endogenous glucose production, primarily hepatic gluconeogenesis, most likely involving the stimulation of AMP-activated protein kinase activity (2). A peripheral insulin-sensitizing effect in skeletal muscle has also been demonstrated by some, but not all, investigators (3). In small studies, metformin appears to exert benefit on various other fundamental biological processes that influence atherogenesis, such as lipid metabolism, inflammation, and vascular endothelial function (4). Another insulin sensitizer category, the thiazolidinediones (TZDs), has also been proposed to reduce CVD risk, but that class carries with it concerns of weight gain and fluid retention. As a result, TZDs remain more popular in combination therapy regimens. Perhaps of greatest import to clinicians is the recognition that metformin is the only oral antidiabetic agent associated with weight loss. Accordingly, metformin remains, in the eyes of many authorities, the optimal initial drug choice in most type 2 diabetic patients if diet and exercise have not succeeded in adequately reducing blood glucose levels (5). Approval of metformin in the U.S. was delayed because of previous experience with phenformin, which was associated with lactic acidosis. Although the risk of such metabolic decompensation with metformin was known to be significantly lower than with Continue reading >>

Cardiovascular Risk Associated With Acarbose Versus Metformin As The First-line Treatment In Patients With Type 2 Diabetes: A Nationwide Cohort Study

Cardiovascular Risk Associated With Acarbose Versus Metformin As The First-line Treatment In Patients With Type 2 Diabetes: A Nationwide Cohort Study

Cardiovascular Risk Associated With Acarbose Versus Metformin as the First-Line Treatment in Patients With Type 2 Diabetes: A Nationwide Cohort Study Institute of Preventive Medicine (C-H.C., S-T.C., L-M.C., M-S.L.), College of Public Health, National Taiwan University, Taipei, Taiwan; Department of Internal Medicine (C-H.C., L-M.C.), Taipei, Taiwan; Department of Medicine (C-H.C., Y-C.C., J-W.L., L-M.C.), College of Medicine, National Taiwan University, Taipei, Taiwan; Search for other works by this author on: Graduate Institute of Medical Genomics and Proteomics (Y-C.C.), National Taiwan University, Taipei, Taiwan; National Taiwan University Hospital, Taipei, Taiwan; Department of Medicine (C-H.C., Y-C.C., J-W.L., L-M.C.), College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Internal Medicine (Y-C.C.), National Taiwan University Hospital, Hsin Chu Branch, HsinChu, Taiwan; Search for other works by this author on: Department of Medicine (C-H.C., Y-C.C., J-W.L., L-M.C.), College of Medicine, National Taiwan University, Taipei, Taiwan; Cardiovascular Center (J-W.L.), National Taiwan University Hospital, Yun-Lin Branch, Dou-Liou City, Yun-Lin County, Taiwan Search for other works by this author on: Institute of Preventive Medicine (C-H.C., S-T.C., L-M.C., M-S.L.), College of Public Health, National Taiwan University, Taipei, Taiwan; Search for other works by this author on: Institute of Preventive Medicine (C-H.C., S-T.C., L-M.C., M-S.L.), College of Public Health, National Taiwan University, Taipei, Taiwan; Department of Internal Medicine (C-H.C., L-M.C.), Taipei, Taiwan; Department of Medicine (C-H.C., Y-C.C., J-W.L., L-M.C.), College of Medicine, National Taiwan University, Taipei, Taiwan; Address all correspondence and requests for reprints Continue reading >>

Clinical Outcomes Of Metformin Use In Populations With Chronic Kidney Disease, Congestive Heart Failure, Or Chronic Liver Disease: A Systematic Review

Clinical Outcomes Of Metformin Use In Populations With Chronic Kidney Disease, Congestive Heart Failure, Or Chronic Liver Disease: A Systematic Review

Abstract Background: Recent changes to the U.S. Food and Drug Administration boxed warning for metformin will increase its use in persons with historical contraindications or precautions. Prescribers must understand the clinical outcomes of metformin use in these populations. Purpose: To synthesize data addressing outcomes of metformin use in populations with type 2 diabetes and moderate to severe chronic kidney disease (CKD), congestive heart failure (CHF), or chronic liver disease (CLD) with hepatic impairment. Data Sources: MEDLINE (via PubMed) from January 1994 to September 2016, and Cochrane Library, EMBASE, and International Pharmaceutical Abstracts from January 1994 to November 2015. Study Selection: English-language studies that: 1) examined adults with type 2 diabetes and CKD (with estimated glomerular filtration rate less than 60 mL/min/1.73 m2), CHF, or CLD with hepatic impairment; 2) compared diabetes regimens that included metformin with those that did not; and 3) reported all-cause mortality, major adverse cardiovascular events, and other outcomes of interest. Data Extraction: 2 reviewers abstracted data and independently rated study quality and strength of evidence. Data Synthesis: On the basis of quantitative and qualitative syntheses involving 17 observational studies, metformin use is associated with reduced all-cause mortality in patients with CKD, CHF, or CLD with hepatic impairment, and with fewer heart failure readmissions in patients with CKD or CHF. Limitations: Strength of evidence was low, and data on multiple outcomes of interest were sparse. Available studies were observational and varied in follow-up duration. Conclusion: Metformin use in patients with moderate CKD, CHF, or CLD with hepatic impairment is associated with improvements in key c Continue reading >>

Medical Xpress: Metformin Tied To Better Clinical Outcomes In Ckd, Chf, Cld

Medical Xpress: Metformin Tied To Better Clinical Outcomes In Ckd, Chf, Cld

Metformin tied to better clinical outcomes in CKD, CHF, CLD (HealthDay)For patients with chronic kidney disease (CKD), congestive heart failure (CHF), or chronic liver disease (CLD) with hepatic impairment, metformin use is associated with improvements in clinical outcomes, according to a review published online Jan. 3 in the Annals of Internal Medicine. Matthew J. Crowley, M.D., from the Durham Veterans Affairs Medical Center and Duke University School of Medicine in North Carolina, and colleagues synthesized data addressing outcomes of metformin use in patients with type 2 diabetes and moderate to severe CKD, CHF, or CLD with hepatic impairment. Data were included from studies that compared diabetes regimens that included metformin with those that did not, and reported all-cause mortality, major adverse cardiovascular events, and other outcomes of interest. The researchers found that metformin use correlated with reduced all-cause mortality in patients with CKD, CHF, or CLD with hepatic involvement on the basis of quantitative and qualitative syntheses involving 17 observational studies. In patients with CKD or CHF, metformin use correlated with fewer heart failure readmissions. "Metformin use in patients with moderate CKD, CHF, or CLD with hepatic impairment is associated with improvements in key clinical outcomes ," the authors write. "Our findings support the recent changes in metformin labeling." Continue reading >>

Drugs That Should Be Avoided Or Used With Caution In Patients With Heart Failure

Drugs That Should Be Avoided Or Used With Caution In Patients With Heart Failure

INTRODUCTION A number of medications that are in common clinical use are relatively or absolutely contraindicated in patients with heart failure (HF), either because they can cause exacerbations of HF or because there is a higher risk of adverse reactions in such patients (table 1) [1]. Drug-induced exacerbation or decompensation of established HF is a relatively common occurrence. Its prevention requires frequent reassessment and meticulous management of often complex medication regimens. Utilization of these drugs is common in patients with HF. In a study from Denmark, 34 percent of patients received at least one nonsteroid anti-inflammatory agent or cyclooxygenase-2 inhibitor after discharge for first hospitalization for HF [2]. Use of some of these drugs may be increasing. As an example, a review of Medicare beneficiaries hospitalized with the diagnoses of HF and diabetes mellitus found that the proportion using metformin and/or a thiazolidinedione increased from 13.5 percent in 1998 to 1999 to 24.4 percent in 2000 to 2001 [3]. Management of patients with HF is discussed separately. (See "Overview of the therapy of heart failure with reduced ejection fraction" and "Treatment and prognosis of heart failure with preserved ejection fraction".) GENERAL PRINCIPLES General principles for avoiding drug-induced worsening of HF include the following: Recognition of the basic mechanisms by which drugs can exacerbate HF including: TI CONTEXT: According to package inserts, metformin is contraindicated in diabetic patients receiving drug treatment for heart failure therapy, and thiazolidinediones are not recommended in diabetic patients with symptoms of advanced heart failure. Little is known about patterns of use of these antihyperglycemic drugs in diabetic patients with heart Continue reading >>

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