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Metformin Debate

Type 2 Nutrition: The Nutrition Debate #274: Should Everyone Take Metformin?

Type 2 Nutrition: The Nutrition Debate #274: Should Everyone Take Metformin?

The Nutrition Debate #274: Should Everyone Take Metformin? I had tolaugh. Of course, by everyone the title of this Medscape piece meant, I thought, as the Initial Choice of OralGlucose-Lowering Medication for [treatment of type 2] Diabetes Mellitus. Butfor a moment I thought that the authors meant everyone everyone.Thats the way thenew guidelines for prescribing statins are being interpreted, at leastfor everyone over 39 years of age (and under 76),and that for the very dubious, almost exclusive purpose of loweringLDL-C. But if you want to read about that, you can go to The Nutrition Debate #180, TheAHA/ACC Cholesterol Guidelines . No, thisstory , published in JAMAInternal Medicine, was an observational cohort study [that] sought todetermine the effect of initial oral glucose-lowering class on subsequent needto additional anti-hyperglycemia therapy. The 15,516 participants, none ofwhom had previously been treated for diabetes, were started on 1) metformin, 2)a sulfonylurea, like glyburide or glipizide, 3) a TZD like Avandia, or 4) aDPP4, like Januvia and Onglyza. The primary outcome was time to treatmentintensification, defined as initiation of a different class of oralglucose-lowering medication, Medscapesaid. Secondaryoutcomes included time to composite cardiovascular event (coronary heartdisease, congestive heart failure, unstable angina, ischemic stroke, acutemyocardial infarction [heart attack], or a revascularization procedure),congestive heart failure alone, an emergency department visit or hospital visitfor hypoglycemia, and any other diabetes related emergency department visit.Thats one heck of a scary list of secondary outcomes. Something to thinkabout TheWinner, and Still Champion: Metformin, the Medscapesub-head declared. Well, there should be no surprise t Continue reading >>

Metformin Ups Survival In T2dm And Cirrhosis

Metformin Ups Survival In T2dm And Cirrhosis

Whether metformin should be discontinued in patients with cirrhosis is an open debate. Some studies point to a protective effect of metformin against liver cancer. Because of concerns over lactic acidosis, though, metformin is often discontinued in patients with cirrhosis. A new study suggests that continuing metformin after a diagnosis of cirrhosis can decrease the risk of death in patients with diabetes by about 57%. “Patients with diabetes who develop cirrhosis and stay on metformin appear to have a better long-term survival than those who are on different anti-diabetic medications, such as insulin, or those that are switched from metformin to insulin,” commented author Lewis Roberts, MB ChB, PhD, Professor of Medicine at the Mayo Clinic College of Medicine in Rochester, Minnesota. “Our results suggest that patients with diabetes who develop cirrhosis can continue to be managed on metformin,” he added, “The use of metformin appears to be safe in most patients with cirrhosis.” Evidence linking metformin to liver injury is “weak,” the authors write. The incidence of lactic acidosis is low in diabetic patients treated with metformin, and is about the same as among diabetic patients not treated with metformin. Moreover, evidence of lactic acidosis in patients with liver disease mainly comes from case reports of patients actively drinking alcohol. The researchers reviewed medical records from 2000 to 2010 to identify patients receiving metformin when they were given a diagnosis of cirrhosis (N=250). They then compared survival between patients who continued metformin for at least 3 months after diagnosis (172 [68.6%]) with those who discontinued metformin within 3 months after diagnosis (n=78 [31.2%]). Patients were followed for approximately 5 years. Key Continue reading >>

Experts Debate Role Of Metformin In Management Of Prediabetes

Experts Debate Role Of Metformin In Management Of Prediabetes

Experts debate role of metformin in management of prediabetes PHILADELPHIA During an academic debate held here, two physicians argued the issue of whether lifestyle changes and metformin are adequate for the management of prediabetes. Richard F. Hamman, MD, DrPH, founding dean and professor of epidemiology at the Colorado School of Public Health, took the pro side, arguing that lifestyle changes and metformin are adequate, using data from the Diabetes Prevention Program (DPP), the Finnish Diabetes Prevention Study (DPS) and other research to bolster his position. Opposite Hamman, Ralph A. DeFronzo, MD, professor of medicine and chief of the diabetes division at the University of Texas Health Science Center and the Audie L. Murphy Memorial VA Hospital in San Antonio, said lifestyle changes are not effective enough for the long-term treatment of patients with diabetes in which metformin is not optimal. Im sure Dr. DeFronzo will look at these data and tell us that weight re-gain means that lifestyle [change] is difficult to achieve. And theres no question [thats true] but these weight loss data have also [demonstrated that a] reduction in diabetes incidence over 10 years is still substantially lower in the lifestyle group, Hamman said. He said the DPP and the DPS data showed lifestyle changes reduced the incidence of diabetes by 58% at 3 years after randomization. Additionally, the 10-year DPPOS follow-up demonstrated that diabetes incidence gradually increased among those without diabetes and at high risk for the disease at the start of the trial. In the placebo group, diabetes incidence increased the most. This is over the entire 10 years, cumulative, Hamman said, adding that diabetes incidence was reduced by 18% over 10 years by metformin and by 34% in the lifestyle gr Continue reading >>

More On Metformin And Cancer (and Alzheimers)

More On Metformin And Cancer (and Alzheimers)

Metformin : what a weird compound it is. Very small, very polar, the sort of thing youd probably cross off your list of screening hits. But its been taken by untold millions of diabetics (and made untold billions of dollars in the process), because it really does reduce glucose levels. It does so though mechanisms that are still the subject of vigorous debate and which (I might add) were completely unknown when the drug was approved. (I keep running into people who think that mechanism-of-action is some sort of FDA requirement, but it most certainly is not. Not saying that it wouldnt help, but what the regulatory agencies want are efficacy and safety. As they should). And evidence has been piling up that the compound does many other things besides. The situation is murky. There was a report in 2009 that suggested that it might exacerbate the pathology of Alzheimers. But last summer there was a rodent study that showed (in obese mice) that the compound seemed to improve neurogenerative effects seen in the hippocampus. (Whether this operates in animals, or humans, who are not metabolically impaired is an open question, although metformin is right in the middle of the whole Type III diabetes debate about Alzheimers, which Im going to cover in another post at some point soon). Meanwhile, human studies (in the large populations taking the drug) are not saying one way or another just yet. This British analysis suggested that there might be an association, but its not for sure. Then theres oncology. In 2010 I wrote about the evidence linking metformin use with lower incidence of some types of cancer, and one proposal for the mechanism. Now another paper is out suggesting that the compound works in this regard through modifying the inflammatory cascade. (Note that James Watson Continue reading >>

Diabetesvoice March 2014 €¢ Volume 59 €¢ Issue 140

Diabetesvoice March 2014 €¢ Volume 59 €¢ Issue 140

coUntry perspectiVes More and more frequently insulin is being recommended as an ‘add-on’ to oral hypoglycaemic therapy for the achievement of blood glucose targets in people with established type 2 diabetes. Indeed, there are now trials of insulin therapy in type 2 diabetes from diagnosis. Concerns have been raised in the recent medical literature that long-term insulin therapy in type 2 diabetes increases the risk of cardiovascular disease and some cancers. We have asked specialists in the fields of clinical diabetes and pharmacoepidemiology to comment on the question: DEBATE: long-term safety of insulin in type 2 diabetes Insulin therapy in people with type 2 diabetes: is it safe in terms of the risk of cardiovascular disease, cancer and all-cause mortality? NO Sarah Holden and Craig Currie Insulin has an unlimited potential to lower blood glucose and is a well- established treatment for type 2 diabetes. The International Diabetes Federation (IDF) recommends that it should be used as an optional third line when a combination of metformin, where indicated, and one other glucose-lowering medi- cation has failed to adequately con- trol blood glucose. ADA and EASD guidelines recommend a patient- centred approach with the aim of achieving adequate glucose control while minimising side effects. Two common side effects associated with insulin injections are weight clinical care DiabetesVoiceMarch 2014 • Volume 59 • Issue 1 41 coUntry perspectiVes gain and hypoglycaemia. Weight gain is associated with an increased risk of cardiovascular disease and should be minimised in type 2 diabetes. Both insulin and hypoglycaemia may have vascular effects which are thought to be greatest in people with pre- existing cardiovascular disease and diabetes.1,2 In add Continue reading >>

Metformin And Ppis: Concurrent Use Seems Acceptable

Metformin And Ppis: Concurrent Use Seems Acceptable

Metformin and PPIs: Concurrent Use Seems Acceptable Metformin has become the cornerstone of oral therapy for Americans epidemic type 2 diabetes mellitus (T2DM). Proton pump inhibitors (PPIs) have similarly become the cornerstone of treatment for our pervasive acid reflux problem. Metformin, a drug that is not metabolized but rather excreted unchanged in the urine, has few interactions. Recently, however, researchers have been debating a potential drug interaction between metformin and the PPIs. The basis of the debate is this: metformin requires hepatocyte uptake using the organic cation transporter (OCT) system to be effective. In vitro research found that PPIs inhibit OCT1, OCT2, and OCT3, creating a concern that PPIs might reduce metformins effectiveness. A study published in the September issue of The British Journal of Clinical Pharmacology found no evidence of such an interaction. This observational cohort study drew data from the UKs Health Improvement Network (THIN) Database that contains data from more than 9 million patients. They used data from 2003 and later because HgA1c testing only became widely available in that year. In the THIN population, they examined 4 groups: Patients who started metformin monotherapy without PPI exposure (n=30,954) Patients who started metformin after having taken PPIs for at least 6 months (n=3,618) Patients who started a PPI without being on any diabetes drug (n=1,396) Patients who started a PPI after at least 180 days of continuous metformin monotherapy (n=801) PPIs did not reduce the effectiveness of metformin. Instead, starting a PPI improved glycemic response by -0.06 HbA1c percentage points. The researchers suggest that PPIs may increase adherence to metformin by ameliorating its gastrointestinal side effects. Patients oft Continue reading >>

Diabetes Debate Leaves Little Consensus

Diabetes Debate Leaves Little Consensus

New guidelines for Type 2 diabetes patients suggests changing a standard for blood-sugar levels that other medical groups still stand by Whats the appropriate blood-sugar target for patients with Type 2 diabetes? The debate heated up on March 6, when a prominent medical association advised relaxing the standard, saying that more aggressive targets can harm patients. The source of the dispute: the hemoglobin A1C test, a test that measures a patients average blood-sugar, or... Copyright 2018 Dow Jones & Company , Inc. All Rights Reserved.

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  • Metformin In Diabetes: Evidence Overwhelming, Or Unclear?

    Metformin In Diabetes: Evidence Overwhelming, Or Unclear?

    Metformin in Diabetes: Evidence Overwhelming, or Unclear? VIENNA The extent of evidence supporting the most widely used, first-line drug for type 2 diabetes, metformin, was the topic under discussion during the Michael Berger debate on the closing day of this year's European Association for the Study of Diabetes (EASD) 2014 Meeting . Synthesized in 1922, with its first trial in 1957, metformin has been available in Europe since 1960 but made its debut in the United States only in 1995. Arguing for the motion, Metformin: Where is the evidence? Rury Holman, MD, director of the University of Oxford Diabetes Trials Unit, United Kingdom, said it isn't clear that there is sufficient proof to support metformin use: "If it were clear, we wouldn't be having this debate." Against the motion, claiming that the existing evidence supports first-line use of metformin, was Harold Lebovitz, MD, professor of medicine at the division of endocrinology and metabolism/diabetes at the State University of New York Health Center, Brooklyn, NY. Dr. Lebovitz took the audience through an extensive tour of trials supporting the use of metformin, beginning with a 1995 study that showed, "It's very effective at improving HbA1c" (N Engl J Med 1995;333: 541-549 ). Dr. Lebovitz then referred to another paper showing that metformin is second only to thiazolidinediones in its durability of action and a lot better than sulfonylureas in this regard (N Engl J Med 2006;355: 2427-2443 ). Regarding the evidence for metformin's use as first-line therapy, Dr. Lebovitz cited a paper by the UK Prospective Diabetes Study (UKPDS) group that concluded: "Since intensive glucose control with metformin appears to decrease the risk of diabetes-related end points in overweight diabetic patients and is associated with les Continue reading >>

    Is It Time To Change The Type 2 Diabetes Treatment Paradigm? No! Metformin Should Remain The Foundation Therapy For Type 2 Diabetes.

    Is It Time To Change The Type 2 Diabetes Treatment Paradigm? No! Metformin Should Remain The Foundation Therapy For Type 2 Diabetes.

    Is It Time to Change the Type 2 Diabetes Treatment Paradigm? No! Metformin Should Remain the Foundation Therapy for Type 2 Diabetes. Yale School of Medicine, New Haven, CT [email protected] Diabetes Care. 2017 Aug;40(8):1128-1132. doi: 10.2337/dc16-2372. Most treatment guidelines, including those from the American Diabetes Association/European Association for the Study of Diabetes and the International Diabetes Federation, suggest metformin be used as the first-line therapy after diet and exercise. This recommendation is based on the considerable body of evidence that has accumulated over the last 30 years, but it is also supported on clinical grounds based on metformin's affordability and tolerability. As such, metformin is the most commonly used oral antihyperglycemic agent in the U.S. However, based on the release of newer agents over the recent past, some have suggested that the modern approach to disease management should be based upon identification of its etiology and correcting the underlying biological disturbances. That is, we should use interventions that normalize or at least ameliorate the recognized derangements in physiology that drive the clinical manifestation of disease, in this circumstance, hyperglycemia. Thus, it is argued that therapeutic interventions that target glycemia but do not correct the underlying pathogenic disturbances are unlikely to result in a sustained benefit on the disease process. In our field, there is an evolving debate regarding the suggested first step in diabetes management and a call for a new paradigm. Given the current controversy, we provide a Point-Counterpoint debate on this issue. In the point narrative that precedes the counterpoint narrative below, Drs. Abdul-Ghani and DeFronzo provide their argument that a Continue reading >>

    Metformin For All? - Diabetes Self-management

    Metformin For All? - Diabetes Self-management

    Since its United States debut in 1995, metformin has overcome initial doubts about its safety to become the recommended first-line drug for Type 2 diabetes, and the most widely prescribed diabetes drug in the world. This massive increase in popularity has been fueled by numerous studies on the drug, which have shown that it may have benefits ranging from weight loss to a lower risk of developing cancer . But some doctors, while generally supportive of the drug as an option for treating Type 2 diabetes, have felt that metformins best-for-everyone reputation is not supported by the evidence currently available. A public debate about the merits of metformin took place earlier this year at the European Association for the Study of Diabetes (EASD) 2014 Meeting in Vienna. As noted in a Medscape article summarizing the debate , the lead skeptic of metformins position as the drug of choice for everyone with Type 2 diabetes was Rury Holman, MD, director of the University of Oxford Diabetes Trials Unit in the United Kingdom. Arguing in favor of metformins first-line position was Harold Lebovitz, MD, professor of medicine at the State University of New York Health Center in Brooklyn, New York. In support of metformin, Lebovitz argues that even though the well regarded UK Prospective Diabetes Study (UKPDS) found metformin to be no more effective at lowering HbA1c than other drugs (including sulfonylureas and insulin ), it was found to be statistically significant in reducing diabetes-related deaths. Lebovitz conceded, however, that since UKPDS there have been no good randomized controlled trials (considered the gold standard for medical evidence) of metformin. And one study, known as HOME, found no difference in cardiovascular outcomes between metformin and a placebo (inactive pil Continue reading >>

    Beyond Metformin: Safety Considerations In The Decision-making Process For Selecting A Second Medication For Type 2 Diabetes Management

    Beyond Metformin: Safety Considerations In The Decision-making Process For Selecting A Second Medication For Type 2 Diabetes Management

    The trend toward personalized management of diabetes has focused attention on the differences among available pharmacological agents in terms of mechanisms of action, efficacy, and, most important, safety. Clinicians must select from these features to develop individualized therapy regimens. In June 2013, a nine-member Diabetes Care Editors’ Expert Forum convened to review safety evidence for six major diabetes drug classes: insulin, sulfonylureas (SUs), thiazolidinediones (TZDs), glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, and sodium glucose cotransporter 2 inhibitors. This article, an outgrowth of the forum, summarizes well-delineated and theoretical safety concerns related to these drug classes, as well as the panelists’ opinions regarding their best use in patients with type 2 diabetes. All of the options appear to have reasonably wide safety margins when used appropriately. Those about which we know the most—metformin, SUs, insulin, and perhaps now also TZDs—are efficacious in most patients and can be placed into a basic initial algorithm. However, these agents leave some clinical needs unmet. Selecting next steps is a more formidable process involving newer agents that are understood less well and for which there are unresolved questions regarding risk versus benefit in certain populations. Choosing a specific agent is not as important as implementing some form of early intervention and advancing rapidly to some form of combination therapy as needed. When all options are relatively safe given the benefits they confer, therapeutic decision making must rely on a personalized approach, taking into account patients’ clinical circumstances, phenotype, pathophysiological defects, preferences, abilities, and costs. © 2014 by t Continue reading >>

    Debates Regarding Lean Patients With Polycystic Ovary Syndrome: A Narrative Review Goyal M, Dawood As - J Hum Reprod Sci

    Debates Regarding Lean Patients With Polycystic Ovary Syndrome: A Narrative Review Goyal M, Dawood As - J Hum Reprod Sci

    Polycystic ovary syndrome (PCOS) affects approximately 412% of women in their reproductive age. It is a leading cause of infertility and is also associated with an increased risk of metabolic syndrome (MBS), diabetes mellitus type 2, cardiovascular disease, and endometrial cancer. [1] A majority (80%) of women with PCOS have an above average or high body mass index (BMI), insulin resistance (IR), and the typical PCOS symptoms (e.g., ovarian cysts, male pattern baldness, acne, and hirsutism). Many of these women are not diagnosed until fertility issues arise in adulthood. Some women with PCOS having a normal, if not low BMI may or may not have IR and exhibit symptoms that are typical to female pubertal maturation during adolescence (e.g., acne, irregular menstrual cycle, and potentially depression). [2] , [3] Literature review was performed using PubMed, Google Scholar, Academia, Mendeley, ClinicalKey, and Cochrane Database from January 1, 2000 to March 31, 2017. Specific MeSH words such as lean PCOS, hormonal abnormalities in lean PCOS, the management of lean PCOS, and diet for lean PCOS were used for searching. PCOS was defined according to Rotterdam criteria. All retrieved articles were carefully assessed, and data were obtained. Insulin resistance in lean women with PCOS Diabetes mellitus, IR, and metabolic abnormalities are all significantly lower in lean women with PCOS. Although IR (IR) is generally agreed to be an underlying cause of PCOS, there is disagreement among the medical community about whether thin women with PCOS suffer from IR to the same degree as their heavier counterparts. For lean women with PCOS, the prevalence of IR was reported to be 622%. [4] , [5] An Indian study proved the presence of abnormal waist circumference and increased waist-to-hip r Continue reading >>

    Metformin For Enhancement - A Hot Area Of Debate For The Future

    Metformin For Enhancement - A Hot Area Of Debate For The Future

    Metformin for Enhancement - A Hot Area of Debate for the Future Metformin is a drug that is used to increase the body's sensitivity to insulin. While normally its usage is limited to diabetes, recent research has implicated that it may be beneficial for enhancement purposes in people that do not have diabetes. A 15-year long observational study showed that metformin was useful for preventing metabolic deficits related to diabetes (resulted in lower BMI and and Hemoglobin A1c values) 1 , and a number of studies have shown that metformin was useful for prolonging lifespan. These findings are prominent and the usage of metformin people that do not have diabetes should be given more emphasis in research and perhaps become a standard of care in the future. Metformin in people that are not diabetic In most medical circles, metformin is reserved for people that have diabetes. However, there is an emerging body of scientific research that shows evidence for the efficacy of metformin for improving longevity and improving insulin sensitivity, even if the body is in a healthy state. A very interesting study was published in 2015 on a 15-year intervention period for 2,776 people at risk (but do not have diabetes). Participants that were identified as having a moderate risk for developing diabetes were given metformin as a preventative measure. This group of participants was matched by a participant group that got placebo treatment, as well as a group that was instructed to make lifestyle modifications (exercise and diet) for prevention purpose. It was found that over a long period of 15 years after starting treatments, the incidence of diabetes in the people that took metformin was dramatically lower than in people that had placebo treatment (60% incidence in placebo, 52% in metfo Continue reading >>

    The Fda And The Ema Allow The Use Of Metformin In Patients With Moderate Renal Impairment

    The Fda And The Ema Allow The Use Of Metformin In Patients With Moderate Renal Impairment

    The FDA and the EMA allow the use of metformin in patients with moderate renal impairment Using metformin in the presence of renal disease BMJ 2015; 350 doi: (Published 14 April 2015) Cite this as: BMJ 2015;350:h1758 The FDA and the EMA allow the use of metformin in patients with moderate renal impairment The FDA and the EMA have both revised warnings regarding the use of metformin in diabetic patients with reduced kidney function, allowing the use of the product for patients with moderate renal function [1-2]. This decision significantly expands the target population using metformin and closes a recurrent debate among diabetologist community, all the more as metformin is often used in clinical practice outside of the current labelling indications. Several authors considered that fear of Metformin-Associated Lactic Acidosis (MALA) was rooted in the history of biguanide-associated lactic acidosis, in particular the experience with phenformin [3] and that the contraindication for metformin in patients with renal insufficiency was too restrictive. Indeed, two recent epidemiological studies have suggested a benefit on mortality in patients with moderate renal impairment using metformin, in accordance with UKPDS results [4]. Compared to other treatments, Roussel et al [5] found a benefit in patients treated by metformin and with eGFR between 30 and 60 ml/min/1.73 m2 (HR = 0.64; 95% CI, 0.48-0.86) whereas Ekstrm et al. [6], of better quality regarding adjustments, found a benefit only in patients with eGFR between 45 to 60 ml/min/1.73 m2 (decrease of mortality of 13%, but wide CI: 0.77-0.99) but not in patients with eGFR between 30 and 45 ml/min/1.73 m2. Nevertheless, it should be noted that the sole randomised study (even underpowered for clinical outcomes), which assessed Continue reading >>

    Metformin In Reproductive Health, Pregnancy And Gynaecological Cancer: Established And Emerging Indications

    Metformin In Reproductive Health, Pregnancy And Gynaecological Cancer: Established And Emerging Indications

    Metformin in reproductive health, pregnancy and gynaecological cancer: established and emerging indications Manchester Academic Health Science Centre, University of Manchester, Central Manchester University Hospitals NHS Foundation Trust Manchester Academic Health Science Centre, University of Manchester, Central Manchester University Hospitals NHS Foundation Trust Leeds Teaching Hospitals, Seacroft Hospital Leeds Teaching Hospitals, Seacroft Hospital Manchester Academic Health Science Centre, University of Manchester, Central Manchester University Hospitals NHS Foundation Trust Correspondence address. Institute of Cancer Sciences, Manchester Academic Health Science Centre, University of Manchester, Central Manchester University Hospitals NHS Foundation Trust, Oxford Road, Manchester M13 9WL, UK. Tel: +44-161-701-6942; E-mail: [email protected] Search for other works by this author on: Human Reproduction Update, Volume 20, Issue 6, 1 November 2014, Pages 853868, Vanitha N. Sivalingam, Jenny Myers, Susie Nicholas, Adam H. Balen, Emma J. Crosbie; Metformin in reproductive health, pregnancy and gynaecological cancer: established and emerging indications, Human Reproduction Update, Volume 20, Issue 6, 1 November 2014, Pages 853868, Metformin is an effective oral anti-hyperglycaemic drug used as first-line medical treatment for type 2 diabetes. It improves systemic hyperglycaemia by reducing hepatic glucose production and enhancing peripheral insulin sensitivity. It also stimulates fat oxidation and reduces fat synthesis and storage. The molecular mechanism of this drug is thought to be secondary to its actions on the mitochondrial respiratory chain. This paper reviews the relevant literature (research articles up to October 2013) on the use of metformin in infe Continue reading >>

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