Comparative Safety And Effectiveness Of Metformin In Patients With Diabetes Mellitus And Heart Failure
Comparative Safety and Effectiveness of Metformin in Patients With Diabetes Mellitus and Heart Failure Systematic Review of Observational Studies Involving 34 000 Patients MD, MScFrom the Department of Public Health Sciences, School of Public Health (D.T.E., D.L.W., R.T.T., J.A.J.), Department of Medicine, Faculty of Medicine and Dentistry (S.R.M., R.T.T., F.A.M.), ACHORD, Li Ka Shing Center, University of Alberta, Edmonton, Alberta, Canada (L.T.); and Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada (S.E.V.). From the Department of Public Health Sciences, School of Public Health (D.T.E., D.L.W., R.T.T., J.A.J.), Department of Medicine, Faculty of Medicine and Dentistry (S.R.M., R.T.T., F.A.M.), ACHORD, Li Ka Shing Center, University of Alberta, Edmonton, Alberta, Canada (L.T.); and Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada (S.E.V.). From the Department of Public Health Sciences, School of Public Health (D.T.E., D.L.W., R.T.T., J.A.J.), Department of Medicine, Faculty of Medicine and Dentistry (S.R.M., R.T.T., F.A.M.), ACHORD, Li Ka Shing Center, University of Alberta, Edmonton, Alberta, Canada (L.T.); and Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada (S.E.V.). From the Department of Public Health Sciences, School of Public Health (D.T.E., D.L.W., R.T.T., J.A.J.), Department of Medicine, Faculty of Medicine and Dentistry (S.R.M., R.T.T., F.A.M.), ACHORD, Li Ka Shing Center, University of Alberta, Edmonton, Alberta, Canada (L.T.); and Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada (S.E.V.). From the Department of Public Health Sciences, School of Public Health (D.T.E., D.L.W., R.T.T., J.A.J.), Department of Medicine, Faculty of 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. Keywords: contraindications , diabetes mellitus , heart failure , metformin , oral hypoglycaemic agents 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] Bolen S, Feldman L, Vassy J, Systematic review: comparative effectiveness and safety of oral medications for type 2 diabetes mellitus. Ann Intern Med 2007;147:386-9 Continue reading >>
Use Of Metformin In Chronic Kidney Disease, Congestive Heart Failure, And Chronic Liver Disease - Curr Med Issues
EVIDENCE-BASED MEDICINE: SUMMARY OF STUDY Year : 2017 | Volume : 15 | Issue : 3 | Page : 240-242 Use of metformin in chronic kidney disease, congestive heart failure, and chronic liver disease Source of Support: None, Conflict of Interest: None . Use of metformin in chronic kidney disease, congestive heart failure, and chronic liver disease. Curr Med Issues 2017;15:240-2 . Use of metformin in chronic kidney disease, congestive heart failure, and chronic liver disease. Curr Med Issues [serial online] 2017 [cited2018 Mar 28];15:240-2. Available from: Source: This is a summary of the study: Clinical Outcomes of Metformin Use in Populations with Chronic Kidney Disease, Congestive Heart Failure, or Chronic Liver Disease: A Systematic Review. Authors: Crowley MJ, Diamantidis CJ, McDuffie JR, Cameron CB, Stanifer JW, Mock CK, et al. Ann Intern Med. 2017 Feb 7;166(3):191-200. doi: 10.7326/M16-1901. Summary prepared by Dr. Ajay Kumar Mishra, Christian Medical College, Vellore, Tamil Nadu, India. Clinical Question: Is metformin safe for use in individuals with chronic kidney disease, congestive heart failure, or chronic liver disease? Authors' conclusion: With appropriate dose optimization, the use of metformin in patients with type 2 diabetes mellitus and moderate chronic kidney disease, congestive heart failure, or chronic liver disease is associated with improvement in clinical outcomes. Case Scenario: A 65-year retired school teacher comes to a general practitioner with her concern regarding her medications. She has well-controlled diabetes, hypertension, dyslipidemia, and chronic kidney disease (CKD). Recently, she had visited another health practitioner who had advised her to stop Glyciphage (metformin) stating that this drug is contraindicated in CKD. What should be the c Continue reading >>
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 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 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 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 >>
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 >>
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 >>
Metformin Use In Patients With Diabetes And Heart Failure: Cause For Concern?
Patients with type 2 diabetes are 2.5 times more likely to develop heart failure than those without diabetes,1 and > 30% of patients with heart failure have concurrent diabetes.2 Biguanides, namely phenformin and metformin, have been used for the treatment of diabetes for decades. In certain clinical situations, however, the use of biguanides can result in an accumulation of lactic acid, which may result in a rare condition known as acute lactic acidosis (ALA), which is fatal in ∼ 50% of cases.3,4 In most instances, the development of ALA arises secondary to conditions predisposing patients to hemodynamic compromise and overt tissue hypoxia, such as acute myocardial infarction (MI), acute uncompromised heart failure, or sepsis.5,6 Phenformin was removed from the market in 1976 because of reports of both fatal and nonfatal phenformin-associated lactic acidosis (PALA).7 The incidence of PALA at the time was estimated to be between 40 and 64 cases per 100,000 patient-years, or four to six times that seen in patients with diabetes who were not on phenformin.8,9 Unlike phenformin, which is metabolized through the liver via hydroxylation, metformin is excreted unchanged in the urine.10 Therefore, metformin is less likely to inhibit hepatic lactate clearance and lead to ALA. The estimated incidence of metformin-associated lactic acidosis (MALA) in patients with diabetes is between 3 and 9 cases per 100,000 patient-years, roughly the same as that reported in patients with diabetes who are not taking a biguanide.4,7,11–13 Epidemiological data reveal that metformin is often used in patients with heart failure. Prospective and retrospective cohort studies have evaluated health care databases of hospitalized and outpatient diabetic populations to determine metformin usage in pa Continue reading >>
Metformin Linked To Decreased Mortality In Ckd, Chf, And Liver Disease
Metformin Linked to Decreased Mortality in CKD, CHF, and Liver Disease Practical Cardiology , Practical Cardiology , Cardiovascular Disease , Heart Failure 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 metformins 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 metformins 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. To evaluate whether metformin use improv 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 >>
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 >>
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 >>
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. 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 drugs 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 est Continue reading >>
