Metformin More Effective Than Sulfonylureas For Reducing Cardiovascular Mortality In Diabetes Patients
Metformin more effective than sulfonylureas for reducing cardiovascular mortality in diabetes patients Metformin more effective than sulfonylureas for reducing cardiovascular mortality in diabetes patients Metformin outperformed sulfonylureas in reducing CVD mortality. For patients with type 2 diabetes, metformin reduces the relative risk of cardiovascular-related mortality by 30% to 40% more than sulfonylureas, according to a meta-analysis published in the Annals of Internal Medicine. "Metformin looks like a clear winner," said Nisa Maruthur, MD, MHS, assistant professor of medicine at the Johns Hopkins University School of Medicine. "This is likely the biggest bit of evidence to guide treatment of type 2 diabetes for the next 2 to 3 years." This review provides an update to 2 previous analyses, the most recent of which was published in 2011. Since then, more than 100 new studies have compared the efficacy of blood sugar-reducing drugs, and several new drugs have been introduced. The study compared the efficacy and safety of monotherapy (thiazolidinediones, metformin, sulfonylureas, dipeptidyl peptidase-4 [DPP-4] inhibitors, sodium-glucose cotransporter 2 [SGLT-2] inhibitors, and glucagon-like peptide-1 [GLP-1] receptor agonists) and several metformin-based combinations in adults with type 2 diabetes. The researchers used data from 204 studies (179 trials and 25 observational studies) that compared monotherapies or metformin-based combination therapies. The studies were identified from MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials from inception through March 2015 (with the MEDLINE search extended through December 2015). After analyzing the data, the researchers found that cardiovascular mortality was lower in patients who used metformin comp Continue reading >>
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Ukpds 34 - Wiki Journal Club
Among overweight patients with T2DM, does metformin reduce DM-related complications and all-cause mortality when compared to diet or other early antiglycemic agents? Among overweight patients with T2DM, metformin reduces the rate of DM-related complications and all-cause mortality when compared to diet alone or other early-generation antiglycemic agents. Biguanides have many theoretical benefits over other agents in the treatment of T2DM including reducing hepatic gluconeogenesis, decreasing plasma insulin levels, and facilitating weight loss. However, the biguanide phenformin was associated with increased CV and all-cause mortality in UGDP (1975) [1] and is no longer used in clinical practice. The related agent metformin subsequently became the subject of intense interest, but studies of metformin's effect on clinical endpoints were lacking. The 1998 UK Prospective Diabetes Study 34 (UKPDS 34) randomized 1,704 overweight patients with newly diagnosed T2DM to one of three arms: conventional therapy with diet alone, intensive therapy with metformin, or intensive therapy with an early-generation antiglycemic agents (chlorpropamide, glibenclamide, or insulin). The primary analysis compared metformin to diet alone, with a secondary analysis comparing metformin to intensive therapy with the other agents. With a median follow-up of 10.7 years, metformin was associated with a reduction in DM-related complications and all-cause mortality when compared to the other two arms of therapy. These benefits persisted at an additional 10 years of follow-up. [2] This study forms the basis for the early administration of metformin among overweight patients with T2DM. Since the publication of UKPDS 34, several generations of antiglycemic agents have been developed, and direct comparisons Continue reading >>
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Metformin Use And Mortality Among Patients With Diabetes And Atherothrombosis
Event curves for all-cause mortality from enrollment to 2 years by metformin use as recorded at baseline. Hazard ratio, 0.67; 95% confidence interval, 0.59-0.75; and adjusted hazard ratio, 0.76; 95% confidence interval, 0.65-0.89 (P<.001 for both, log-rank test). Hazard ratios are adjusted for age and sex. Adjusted hazard ratios are adjusted for significant risk factors in univariate analysis and for propensity score. Number of patients is slightly different from those of Table 1 (in which all cohort individuals at baseline were included in the descriptive statistics). For the Figures and outcomes analysis, cohort individuals with at least 1 follow-up datum on vital status were included. Hazard ratios (HRs) for mortality associated with metformin use as recorded at baseline adjusted for significant risk factors in univariate analysis and for propensity score and stratified by relevant clinical categories. Black boxes indicate hazard ratios, and their sizes are representative of patient numbers. Horizontal lines indicate 95% confidence intervals (CIs). CHF indicates congestive heart failure; eGFR, estimated glomerular filtration rate; and TZDs, thiazolidinediones. Number of patients is slightly different from those of Table 1 (in which all cohort individuals at baseline were included in the descriptive statistics). For the Figures and outcomes analysis, cohort individuals with at least 1 follow-up datum on vital status were included. Baseline Characteristics of the Study Population by Metformin Usea Continue reading >>
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Impact Of Metformin On Cardiovascular Disease: A Meta-analysis Of Randomised Trials Among People With Type 2 Diabetes
, Volume 60, Issue9 , pp 16201629 | Cite as Impact of metformin on cardiovascular disease: a meta-analysis of randomised trials among people with type 2 diabetes Metformin is the most-prescribed oral medication to lower blood glucose worldwide. Yet previous systematic reviews have raised doubts about its effectiveness in reducing risk of cardiovascular disease, the most costly complication of type 2 diabetes. We aimed to systematically identify and pool randomised trials reporting cardiovascular outcomes in which the effect of metformin was isolated through comparison to diet, lifestyle or placebo. We performed an electronic literature search of MEDLINE, EMBASE and the Cochrane Library. We also manually screened the reference lists of previous meta-analyses of trials of metformin identified through a MEDLINE search. We included randomised controlled trials of adults with type 2 diabetes comparing any dose and preparation of oral metformin with no intervention, placebo or a lifestyle intervention and reporting mortality or a cardiovascular outcome. We included ten articles reporting 13 trials (including a total of 2079 individuals with type 2 diabetes allocated to metformin and a similar number to comparison groups) of which only four compared metformin with placebo and collected data on cardiovascular outcomes. Participants were mainly white, aged 65years, overweight/obese and with poor glycaemic control. Summary estimates were based on a small number of events: 416 myocardial infarctions/ischaemic heart disease events in seven studies and 111 strokes in four studies. The UK Prospective Diabetes Study (UKPDS) contributed the majority of data to the summary estimates, with weights ranging from 52.3% for myocardial infarction to 70.5% for stroke. All outcomes, with the e Continue reading >>
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Mortality And Metformin Use In Patients With Advanced Chronic Kidney Disease – Authors' Reply
We appreciate the comments by Jean-Daniel Lalau and colleagues on our study.1 Our conclusion in the report was actually in line with their contention that metformin treatment should be withdrawn in unstable patients with stage 4–5 chronic kidney disease. Additionally, we further indicated that the risk of metabolic acidosis, a major medical concern, did not differ between metformin users and non-users. Our results are in agreement with those of previous studies2 and systematic reviews.3 We estimated the duration of diabetes from Taiwan's National Health Insurance Research Database from 1998 onwards. Therefore, we might have underestimated the true duration of diabetes. The prevalence of diabetic retinopathy in our study was 35%, which is in agreement with previously published Taiwanese epidemiological data,4 and confirms that the population studied is representative. We agree with Lalau and colleagues that metformin might accumulate in patients with chronic kidney disease. However, cutoff values for serum creatinine and maximum metformin daily dose recommended in existing guidelines are based on opinion rather than evidence. What would constitute an unsafe serum creatinine concentration is not really known. In fact, clinicians often need to check and find a balance between achieving glycaemic control and limiting adverse effects of metformin within the constraints of rigid guidelines. Interestingly, the proportion of patients using metformin despite having an estimated glomerular filtration rate lower than 30 mL/min per 1·73 m², at which metformin use is discouraged, remained as high as 18% in a recent study examining National Health and Nutrition Examination Survey data from 2007 to 2012 in the USA.5 The mean number of antidiabetes drugs used per patient was 1·6 i Continue reading >>
Ada: Mortality Lower With Metformin
ORLANDO -- Metformin use may reduce mortality among patients with type 2 diabetes who are at risk for cardiovascular events, researchers say. by Kristina Fiore Kristina Fiore, Staff Writer, MedPage Today Explain that patients with type 2 diabetes taking metformin appeared to have a 24% lower risk of death from any cause than patients who weren't taking it. Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal. ORLANDO -- Metformin use may reduce mortality among patients with type 2 diabetes who are at risk for cardiovascular events, researchers say. A large, multicenter trial found a 24% reduced risk of all-cause mortality among patients on the drug, compared with those not taking it, according to Ronan Roussel, MD, PhD, of Groupe Hospitalier Bichat-Claude Bernard in Paris, and colleagues. They presented their findings during a late-breaking session at the American Diabetes Association (ADA) meeting here. "In secondary prevention patients, the use of metformin was associated with a significant reduction in all-cause mortality after two years of follow-up," Roussel said. Previous studies, including the United Kingdom Prospective Diabetes Study (UKPDS) have suggested that metformin may carry a decreased risk of overall mortality. To explore the relationship, Roussel and colleagues assessed data from the Reduction of Atherosclerosis for Continued Health (REACH) registry, which enrolled more than 67,000 patients from 5,473 sites in 44 countries. Its purpose was to investigate risk factors for cardiovascular events in patients at risk of atherothrombotic disease and to assess the use of risk management strategies. In this analysis, the Rous Continue reading >>
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Could Metformin Be The First Anti-aging Drug?
Could Metformin be the First Anti-Aging Drug? I would pay you if you took it away from me. Id try to buy it back, said Irving Kahn, the late Wall Street investment advisor when asked if he would ever retire from work [1]. Mr. Kahn, who founded Kahn Brothers Group, Inc. with his sons more than 40 years ago, took an active role as chair of his company until his passing last winter at the ripe age of 109 years. Kahn and his siblings all lived to be centenarians and were enrolled in the Longevity Genes Project at the Albert Einstein College of Medicines Institute for Aging Research, with more than 500 healthy seniors between the ages of 95 and 112 and their children [2]. The project aims to identify the longevity genes that allow super agers to live far beyond their age-matched peers despite unhealthy behaviors such as cigarette smoking. In hopes of discovering therapies that target the aging process, Dr. Nir Barzilai and his colleagues at the Institute for Aging Research are looking to make a cheap, generic, widely used drugmetforminthe first to be Food and Drug Association (FDA)-approved for the indication of aging. Metformin is an oral biguanide antidiabetic medication that has been used for over 50 years. It is commonly prescribed as a first-line treatment for type 2 diabetes mellitus and often in combination with other antidiabetic medications including insulin. Metformin reduces blood glucose levels by preventing glucose production in the liver and increasing peripheral glucose utilization. Lower glucose levels lead to lower levels of insulin and insulin-like growth factor 1 (IGF-1), thereby increasing the bodys sensitivity to insulin [3-5]. High blood glucose and insulin levels are important factors in aging and cancer [6-8]. Inactivation of insulin and insulin-like 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 >>
Management Of Blood Glucose With Noninsulin Therapies In Type 2 Diabetes
A comprehensive, collaborative approach is necessary for optimal treatment of patients with type 2 diabetes mellitus. Treatment guidelines focus on nutrition, exercise, and pharmacologic therapies to prevent and manage complications. Patients with prediabetes or new-onset diabetes should receive individualized medical nutrition therapy, preferably from a registered dietitian, as needed to achieve treatment goals. Patients should be treated initially with metformin because it is the only medication shown in randomized controlled trials to reduce mortality and complications. Additional medications such as sulfonylureas, dipeptidyl-peptidase-4 inhibitors, thiazolidinediones, and glucagon-like peptide-1 receptor agonists should be added as needed in a patient-centered fashion. However, there is no evidence that any of these medications reduce the risk of diabetes-related complications, cardiovascular mortality, or all-cause mortality. There is insufficient evidence on which combination of hypoglycemic agents best improves health outcomes before escalating to insulin therapy. The American Diabetes Association recommends an A1C goal of less than 7% for many nonpregnant adults, with the option of a less stringent goal of less than 8% for patients with short life expectancy, cardiovascular risk factors, or long-standing diabetes. Randomized trials in middle-aged patients with cardiovascular risk factors have shown no mortality benefit and in some cases increased mortality with more stringent A1C targets. Clinical recommendation Evidence rating References Metformin should be used as first-line therapy to reduce microvascular complications, assist in weight management, reduce the risk of cardiovascular events, and reduce the risk of mortality in patients with type 2 diabetes mell Continue reading >>
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 >>
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Effect Of Metformin On Cardiovascular Events And Mortality: A Meta-analysis Of Randomized Clinical Trials.
Effect of metformin on cardiovascular events and mortality: a meta-analysis of randomized clinical trials. Lamanna C, et al. Diabetes Obes Metab. 2011. Diabetes Agency, Careggi Teaching Hospital, Florence, Italy. Diabetes Obes Metab. 2011 Mar;13(3):221-8. doi: 10.1111/j.1463-1326.2010.01349.x. AIM: Some studies suggested that metformin could reduce cardiovascular risk to a greater extent than that determined by glucose reduction. Aim of the present meta-analysis is to assess the effects of metformin on the incidence of cardiovascular events and mortality. METHODS: An extensive search of Medline, EMBASE and the Cochrane Library (any date up to 31 October 2009) was performed for all trials containing the word 'metformin'. Randomized trials with a duration 52 weeks were included. A meta-regression analysis was also performed to identify factors associated with cardiovascular morbidity and mortality in metformin-treated patients. RESULTS: A total of 35 clinical trials were selected including 7171 and 11 301 participants treated with metformin and comparator, respectively, who had 451 and 775 cardiovascular (CV) events, respectively. Overall, metformin was not associated with significant harm or benefit on cardiovascular events (MH-OR 0.94[0.82-1.07], p = 0.34). A significant benefit was observed in trials versus placebo/no therapy (MH-OR 0.79[0.64-0.98], p = 0.031), but not in active-comparator trials (MH-OR 1.03[0.72-1.77], p = 0.89). Meta-regression showed a significant correlation of the effect of metformin on cardiovascular events with trial duration and with minimum and maximum age for inclusion, meaning that the drug appeared to be more beneficial in longer trials enrolling younger patients. It is likely that metformin monotherapy is associated with improved survival Continue reading >>
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Metformin: An Old But Still The Best Treatment For Type 2 Diabetes
Abstract The management of T2DM requires aggressive treatment to achieve glycemic and cardiovascular risk factor goals. In this setting, metformin, an old and widely accepted first line agent, stands out not only for its antihyperglycemic properties but also for its effects beyond glycemic control such as improvements in endothelial dysfunction, hemostasis and oxidative stress, insulin resistance, lipid profiles, and fat redistribution. These properties may have contributed to the decrease of adverse cardiovascular outcomes otherwise not attributable to metformin’s mere antihyperglycemic effects. Several other classes of oral antidiabetic agents have been recently launched, introducing the need to evaluate the role of metformin as initial therapy and in combination with these newer drugs. There is increasing evidence from in vivo and in vitro studies supporting its anti-proliferative role in cancer and possibly a neuroprotective effect. Metformin’s negligible risk of hypoglycemia in monotherapy and few drug interactions of clinical relevance give this drug a high safety profile. The tolerability of metformin may be improved by using an appropiate dose titration, starting with low doses, so that side-effects can be minimized or by switching to an extended release form. We reviewed the role of metformin in the treatment of patients with type 2 diabetes and describe the additional benefits beyond its glycemic effect. We also discuss its potential role for a variety of insulin resistant and pre-diabetic states, obesity, metabolic abnormalities associated with HIV disease, gestational diabetes, cancer, and neuroprotection. Introduction The discovery of metformin began with the synthesis of galegine-like compounds derived from Gallega officinalis, a plant traditionally em Continue reading >>
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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 >>
Variations In Metformin Prescribing For Type 2 Diabetes
Abstract Background: Reasons for suboptimal metformin prescribing are unclear, but may be due to perceived risk of lactic acidosis. The purpose of this study is to describe provider attitudes regarding metformin prescribing in various patient situations. Methods: An anonymous, electronic survey was distributed electronically to 76 health care providers across the nation. The 14-item survey contained demographic questions and questions related to prescribing of metformin for T2DM in various patient situations, including suboptimal glycemic control, alcohol use, history of lactic acidosis, and varying degrees of severity for certain health conditions, including renal and hepatic dysfunction, chronic obstructive pulmonary disease, and heart failure. Results: There were a total of 100 respondents. For suboptimal glycemic control, most providers (75%) would increase metformin from 1500 to 2000 mg daily; however, 25% would add an alternate agent, such as a sulfonylurea (18%) or dipeptidyl peptidase-4 inhibitor (7%). Although 51% of providers would stop metformin based on serum creatinine thresholds, the remainder would rely on glomerular filtration rate thresholds of <60 mL/min (15%), <30 mL/min (33%), or <15 mL/min (1%) to determine when to stop metformin. For heart failure, 45% of providers would continue metformin as currently prescribed regardless of severity. Most providers would adjust metformin for varying severity of hepatic dysfunction (74%) and alcohol abuse (40%). Conclusions: Despite evidence supporting the cardiovascular benefits of metformin, provider attitudes toward prescribing metformin are suboptimal in certain patient situations and vary greatly by provider. Methods A 14-item survey was developed and modified based on feedback from a small focus group of pr Continue reading >>
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Survival Benefit Associated With Metformin Use In Inoperable Non-small Cell Lung Cancer Patients With Diabetes: A Population-based Retrospective Cohort Study
Click through the PLOS taxonomy to find articles in your field. For more information about PLOS Subject Areas, click here . Survival benefit associated with metformin use in inoperable non-small cell lung cancer patients with diabetes: A population-based retrospective cohort study Roles Conceptualization, Investigation, Writing original draft Affiliations Department of Pulmonary and Critical Care Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan, Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan City, Taiwan Roles Data curation, Formal analysis, Funding acquisition, Methodology, Software Affiliations Department of Traditional Chinese Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan, Health Information and Epidemiology Laboratory of Chang Gung Memorial Hospital, Chiayi, Taiwan, School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan Affiliation Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Kaohsiung, Taiwan Affiliation Department of Pulmonary and Critical Care Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan Affiliation Department of Pulmonary and Critical Care Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan Affiliation Department of Pulmonary and Critical Care Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan Continue reading >>
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- Early Glycemic Control and Magnitude of HbA1c Reduction Predict Cardiovascular Events and Mortality: Population-Based Cohort Study of 24,752 Metformin Initiators
