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Metformin Resistance Over Time

Metformin

Metformin

Metformin, marketed under the trade name Glucophage among others, is the first-line medication for the treatment of type 2 diabetes,[4][5] particularly in people who are overweight.[6] It is also used in the treatment of polycystic ovary syndrome.[4] Limited evidence suggests metformin may prevent the cardiovascular disease and cancer complications of diabetes.[7][8] It is not associated with weight gain.[8] It is taken by mouth.[4] Metformin is generally well tolerated.[9] Common side effects include diarrhea, nausea and abdominal pain.[4] It has a low risk of causing low blood sugar.[4] High blood lactic acid level is a concern if the medication is prescribed inappropriately and in overly large doses.[10] It should not be used in those with significant liver disease or kidney problems.[4] While no clear harm comes from use during pregnancy, insulin is generally preferred for gestational diabetes.[4][11] Metformin is in the biguanide class.[4] It works by decreasing glucose production by the liver and increasing the insulin sensitivity of body tissues.[4] Metformin was discovered in 1922.[12] French physician Jean Sterne began study in humans in the 1950s.[12] It was introduced as a medication in France in 1957 and the United States in 1995.[4][13] It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system.[14] Metformin is believed to be the most widely used medication for diabetes which is taken by mouth.[12] It is available as a generic medication.[4] The wholesale price in the developed world is between 0.21 and 5.55 USD per month as of 2014.[15] In the United States, it costs 5 to 25 USD per month.[4] Medical uses[edit] Metformin is primarily used for type 2 diabetes, but is increasingly be Continue reading >>

Metformin: Improving Insulin Sensitivity

Metformin: Improving Insulin Sensitivity

Metformin is the only medication in the biguanides category of blood glucose-lowering drugs approved by the U.S. Food and Drug Administration (FDA). Metformin has been available in the United States since the mid-1990s, when it received FDA approval. You may also know it by its brand name when it was under patent, Glucophage. Metformin is now widely available as a relatively inexpensive generic medication. Metformin’s main action is to decrease the overproduction of glucose by the liver, a common problem in prediabetes and type 2 diabetes. The action of metformin helps lower blood sugar levels particularly during the night to keep fasting glucose levels under control, but it also helps control blood glucose throughout the day. Metformin also increases the uptake of glucose by your muscles. Overall, metformin decreases insulin resistance and improves insulin sensitivity, thereby helping the insulin your body still makes work more effectively. People with prediabetes and in the early years of type 2 diabetes often continue to make some insulin, just not enough to control blood sugar levels alone. Metformin is not formally approved for use in prediabetes, and any use to treat prediabetes is considered off-label by providers. Since its approval, metformin has become the most commonly recommended blood glucose-lowering medication to treat type 2 diabetes. In recent years it has significantly replaced sulfonylureas, such as glipizide and glyburide. Today both the American Diabetes Association (ADA), the European Association for the Study of Diabetes (EASD), and the American Association of Clinical Endocrinologists (AACE) generally recommend that people with type 2 diabetes start taking metformin when they are diagnosed to help treat insulin resistance and maximize insulin s Continue reading >>

Effect Of Pioglitazone Compared With Metformin On Glycemic Control And Indicators Of Insulin Sensitivity In Recently Diagnosed Patients With Type 2 Diabetes

Effect Of Pioglitazone Compared With Metformin On Glycemic Control And Indicators Of Insulin Sensitivity In Recently Diagnosed Patients With Type 2 Diabetes

Pioglitazone, a thiazolidinedione, improves glycemic control primarily by increasing peripheral insulin sensitivity in patients with type 2 diabetes, whereas metformin, a biguanide, exerts its effect primarily by decreasing hepatic glucose output. In the first head-to-head, double-blind clinical trial comparing these two oral antihyperglycemic medications (OAMs), we studied the effect of 32-wk monotherapy on glycemic control and insulin sensitivity in 205 patients with recently diagnosed type 2 diabetes who were naive to OAM therapy. Subjects were randomized to either 30 mg pioglitazone or 850 mg metformin daily with titrations upward to 45 mg (77% of pioglitazone patients) and 2550 mg (73% of metformin patients), as indicated, to achieve fasting plasma glucose levels of less than 7.0 mmol/liter (126 mg/dl). Pioglitazone was comparable to metformin in improving glycemic control as measured by hemoglobin A1C and fasting plasma glucose. At endpoint, pioglitazone was significantly more effective than metformin in improving indicators of insulin sensitivity, as determined by reduction of fasting serum insulin (P = 0.003) and by analysis of homeostasis model assessment for insulin sensitivity (HOMA-S; P = 0.002). Both OAM therapies were well tolerated. Therefore, pioglitazone and metformin are equally efficacious in regard to glycemic control, but they exert significantly different effects on insulin sensitivity due to differing mechanisms of action. The more pronounced improvement in indicators of insulin sensitivity by pioglitazone, as compared with metformin monotherapy in patients recently diagnosed with type 2 diabetes who are OAM-naive, may be of interest for further clinical evaluation. Most studies of sex hormones and insulin resistance (IR) have focused on androgens Continue reading >>

Metformin 101: Blood Sugar Levels, Weight, Side Effects

Metformin 101: Blood Sugar Levels, Weight, Side Effects

As a type 2 diabetic, you've probably heard of Metformin, or you might even be taking it yourself. Metformin (brand name “Glucophage” aka “glucose-eater”) is the most commonly prescribed medication for type 2 diabetes worldwide…and for good reason. It is one of the safest, most effective, least costly medication available with minimal, if any, side effects. There are always lots of questions around Metformin – how does metformin lower blood sugar, does metformin promote weight loss or weight gain, will it give me side effects – and lots more. Today we'll hopefully answer some of those questions. How Metformin Works Metformin belongs to a class of medications known as “Biguanides,” which lower blood glucose by decreasing the amount of sugar put out by the liver. The liver normally produces glucose throughout the day in conjunction with the pancreas’ production of insulin to maintain stable blood sugar. In many people with diabetes, both mechanisms are altered in that the pancreas puts out less insulin while the liver is unable to shut down production of excess glucose. This means your body is putting out as much as 3 times as much sugar than that of nondiabetic individuals, resulting in high levels of glucose in the bloodstream. Metformin effectively shuts down this excess production resulting in less insulin required. As a result, less sugar is available for absorption by the muscles and conversion to fat. Additionally, a lower need for insulin slows the progression of insulin resistance and keeps cells sensitive to endogenous insulin (that made by the body). Since metformin doesn’t cause the body to generate more insulin, it does not cause hypoglycemia unless combined with a sulfonylurea or insulin injection. Metformin is one of the few oral diabe Continue reading >>

Reckoning With Statin-induced Diabetes And Metformin Resistance

Reckoning With Statin-induced Diabetes And Metformin Resistance

Every year, hundreds of billions of dollars are spent to discover new synthetic pharmaceutical agents and technologies intended to improve health; yet the burden of chronic disease continues unabated. Simply put, these interventions do not address the root causes of the most troublesome diseases. In fact, many pharmaceuticals place additional burden upon the very metabolic buffering systems they are intended to help. Rather than working with the body to build up metabolic reserve, the most commonly used—and most well-reimbursed--therapies often stretch physiological resilience to a breaking point. Consider, for example, the FDA's recent requirement for additional label warnings on all statin drugs. The first is a warning that statin use can increase glycosylated hemoglobin (HbA1c), a marker of worsening blood glucose control. The second states that statin use increases memory loss and confusion, which abates once statins are discontinued. Some doctors—and of course patients—have known about these "new" risks for years prior to FDA's mandated label changes. Yet, in the weeks following FDA's announcement, a number of prominent clinicians came out with statements dismissing the relevance of this warning, even criticizing FDA for potentially leading doctors to think twice before giving statins. Statins are proven life-savers, these pundits reminded us. Who wouldn't want to give them to everyone? After all, if you are concerned about diabetes risk, you can just add metformin to your statin prescription! So comfortable have some clinicians become with the "expected" side-effects of pharmaceuticals, that this type of thinking goes virtually unquestioned. But question it we must. Challenging "Oedipus Rx" In the largest diabetes prevention trial to date, the Diabetes Preve Continue reading >>

Insulin Resistance

Insulin Resistance

What medical conditions are associated with insulin resistance? While the metabolic syndrome links insulin resistance with abdominal obesity, elevated cholesterol, and high blood pressure; several other medical other conditions are specifically associated with insulin resistance. Insulin resistance may contribute to the following conditions: Type 2 Diabetes: Overt diabetes may be the first sign insulin resistance is present. Insulin resistance can be noted long before type 2 diabetes develops. Individuals reluctant or unable to see a health-care professional often seek medical attention when they have already developed type 2 diabetes and insulin resistance. Fatty liver: Fatty liver is strongly associated with insulin resistance. Accumulation of fat in the liver is a manifestation of the disordered control of lipids that occurs with insulin resistance. Fatty liver associated with insulin resistance may be mild or severe. Newer evidence suggests fatty liver may even lead to cirrhosis of the liver and, possibly, liver cancer. Arteriosclerosis: Arteriosclerosis (also known as atherosclerosis) is a process of progressive thickening and hardening of the walls of medium-sized and large arteries. Arteriosclerosis is responsible for: Other risk factors for arteriosclerosis include: High levels of "bad" (LDL) cholesterol Diabetes mellitus from any cause Family history of arteriosclerosis Skin Lesions: Skin lesions include increased skin tags and a condition called acanthosis nigerians (AN). Acanthosis nigricans is a darkening and thickening of the skin, especially in folds such as the neck, under the arms, and in the groin. This condition is directly related to the insulin resistance, though the exact mechanism is not clear. Acanthosis nigricans is a cosmetic condition strongly Continue reading >>

Medication For Type 2 Diabetes

Medication For Type 2 Diabetes

People with type 2 diabetes are often given medications including insulin to help control their blood glucose levels. Most of these medications are in the form of tablets, but some are given by injection. Tablets or injections are intended to be used in conjunction with healthy eating and regular physical activity, not as a substitute. Diabetes tablets are not an oral form of insulin.Speak with your doctor or pharmacist if you experience any problems. An alternative medication is usually available. All people with diabetes need to check their glucose levels on a regular basis. When taking medication, you may need to check your glucose levels more often to keep you safe and to ensure the medication is having the desired effect. In Australia there are seven classes of medicines used to treat type 2 diabetes: Biguanides Sulphonylureas Thiazolidinediones (Glitazones) Alpha-glucosidase Inhibitors. Dipeptidyl peptidase 4 (DPP4) inhibitors Incretin mimetics Sodium-glucose transporter (SGLT2) inhibitors Your doctor will talk to you about which tablets are right for you, when to take your tablets and how much to take. Your doctor can also tell you about any possible side effects. You should speak to your doctor or pharmacist if you experience any problems. Chemical name: METFORMIN , METFORMIN ER Points to remember about biguanides This group of insulin tablets helps to lower blood glucose levels by reducing the amount of stored glucose released by the liver, slowing the absorption of glucose from the intestine, and helping the body to become more sensitive to insulin so that your own insulin works better They need to be started at a low dose and increased slowly Metformin is often prescribed as the first diabetes tablet for people with type 2 diabetes who are overweight. It gene Continue reading >>

New Findings About What Metformin Really Does

New Findings About What Metformin Really Does

As many of my readers know, there is no requirement that the companies that sell pharmaceutical drugs provide an accurate explanation of what it is that their drugs do or of how they do it. All that they have to prove is that the drug has an impact on some measurable phenomenon. The company may claim that a drug functions using a mechanism that is later proven to be untrue. This has been the case with the SSRI drugs which it turned out actually work by remodelling the nerves in the hippocampus, NOT by changing levels of serotonin. Metformin, which has been used for decades, is another drug whose effect is well understood--it lowers blood sugar and reduces the amount of insulin needed to lower blood sugar. This has been interpreted to mean that it lowers insulin resistance. But new findings are calling this into question, as we discover that metformin may actually be stimulating insulin release or blocking the liver's release of glucose rather than impacting insulin resistant cell receptors. The first finding is one I stumbled over recently, one which seems to have gone unnoticed by the medical press. It is that metformin appears to boost GLP-1 levels. GLP-1 is an incretin hormone secreted in the gut which stimulates the beta cell to secrete insulin in the presence of high blood sugars. GLP-1 may also lower glucagon production at the same time. While Byetta and Januvia are higly promoted as being incretin drugs, some little known research suggests that metformin may also raise the level of GLP-1 in the body. Enhanced secretion of glucagon-like peptide 1 by biguanide compounds. Yasuda N et al. Biochem Biophys Res Commun. 2002 Nov 15;298(5):779-84. This was old news, but it may partially explain some of the stomach symptoms people experience with metformin. GLP-1 stops or Continue reading >>

Could Metformin Actually Make Insulin Resistance Worse?

Could Metformin Actually Make Insulin Resistance Worse?

Polycystic Ovarian Syndrome, or PCOS, and Insulin Resistance (IR) often occur simultaneously. While the connection between these two conditions is, as of yet, not entirely clear, researchers have determined that IR can lead to PCOS and diabetes.1 Metformin, or Glucophage, is commonly prescribed for both of these disorders, as it is assumed to reduce IR and improve the symptoms associated with it (such as high blood sugar). Understanding the Fine Print Although Metformin claims to reduce IR, current labeling laws do not require pharmaceutical companies to reveal how their products achieve results, they simply must accurately represent what kind of results can be expected from their medications.2 This pharmaceutical, in particular, lowers blood sugar using less insulin, which has been taken to mean that it reduces IR.2 This may not be the case. How Does Metformin Really Work? Diabetes Update, a blog that reviews diabetes medications and treatment options, has published some interesting findings pertaining to how Metformin actually improves diabetes and PCOS. A study conducted on mice has suggested that the drug lowers blood sugar not by reducing IR, but by activating a gene that does not function properly. This gene, which is located in the liver, stops the production of glucose.2 According to the findings of this study, this pharmaceutical works on a deeper level than simply increasing the sensitivity of the body’s cells to insulin—it actually addresses a genetic issue. While the end result remains the same, blood sugar is lowered; the cells of the body are no more sensitive to insulin than they were before. Although the desired end result is achieved, this doesn’t necessarily heal the body in the same manner as decreasing IR would. Determining Which PCOS Medicine Continue reading >>

Pro/con: Metformin For Pediatric Patients With Insulin Resistance

Pro/con: Metformin For Pediatric Patients With Insulin Resistance

Is metformin a much-needed treatment for pediatric patients or an ineffective substitute for lifestyle intervention? Although metformin is widely-used as a treatment for adults with diabetes and insulin resistance, its use in pediatric patients is somewhat controversial. At the Pediatric Academic Societies’ 2006 Annual Meeting, held recently in San Francisco, two leading physicians debated the use of metformin as a treatment for insulin resistance in pediatric patients. Michael Freemark, MD, chief of the division of endocrinology and diabetes in the pediatrics department of Duke University Medical Center, said he supports metformin treatment in pediatric patients. In contrast, Philip Scott Zeitler, MD, PhD, associate professor of pediatrics at the University of Colorado School of Medicine, was opposed to metformin treatment in this population, saying lifestyle interventions should be encouraged for these patients. A needed treatment? Freemark said metformin can and should be used to treat selected pediatric patients with insulin resistance. “We are dealing with a very serious problem,” he said. “This can be seen in the recent surges in the complications of obesity and insulin resistance among pediatric patients, including type 2 diabetes, dyslipidemia and hypertension. We must intervene effectively and, given the progressive nature of these conditions, we cannot dally.” Freemark warned that if treatments for this patient population are not improved soon, there may be an increase in consequences such as cardiovascular disease and malignancy at earlier ages. Like most physicians, Freemark agreed that lifestyle interventions, including improved diet and increased physical activity, should be the first treatment for all patients with obesity or insulin resistance. Continue reading >>

Metformin: An Old But Still The Best Treatment For Type 2 Diabetes

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 >>

Long-term Treatment With Metformin In Obese, Insulin-resistant Adolescents: Results Of A Randomized Double-blinded Placebo-controlled Trial

Long-term Treatment With Metformin In Obese, Insulin-resistant Adolescents: Results Of A Randomized Double-blinded Placebo-controlled Trial

As adolescents with obesity and insulin resistance may be refractory to lifestyle intervention therapy alone, additional off-label metformin therapy is often used. In this study, the long-term efficacy and safety of metformin versus placebo in adolescents with obesity and insulin resistance is studied. In a randomized placebo-controlled double-blinded trial, 62 adolescents with obesity aged 10–16 years old with insulin resistance received 2000 mg of metformin or placebo daily and physical training twice weekly over 18 months. Primary end points were change in body mass index (BMI) and insulin resistance measured by the Homeostasis Model Assessment for Insulin Resistance (HOMA-IR). Secondary end points were safety and tolerability of metformin. Other end points were body fat percentage and HbA1c. Forty-two participants completed the 18-month study (66% girls, median age 13 (12–15) years, BMI 30.0 (28.3 to 35.0) kg m−2 and HOMA-IR 4.08 (2.40 to 5.88)). Median ΔBMI was +0.2 (−2.9 to 1.3) kg m−2 (metformin) versus +1.2 (−0.3 to 2.4) kg m−2 (placebo) (P=0.015). No significant difference was observed for HOMA-IR. No serious adverse events were reported. Median change in fat percentage was −3.1 (−4.8 to 0.3) versus −0.8 (−3.2 to 1.6)% (P=0.150), in fat mass −0.2 (−5.2 to 2.1) versus +2.0 (1.2–6.4) kg (P=0.007), in fat-free mass +2.0 (−0.1 to 4.0) versus +4.5 (1.3 to 11.6) kg (P=0.047) and in ΔHbA1c +1.0 (−1.0 to 2.3) versus +3.0 (0.0 to 5.0) mmol mol−1 (P=0.020) (metformin versus placebo). Long-term treatment with metformin in adolescents with obesity and insulin resistance results in stabilization of BMI and improved body composition compared with placebo. Therefore, metformin may be useful as an additional therapy in combination with lifes Continue reading >>

New Information On How Metformin Works

New Information On How Metformin Works

Not only has new research told us how metformin really works, but a new biomarker was found that can determine the optimal dose of metformin that should be used to get the best results for each patient. Research from the Johns Hopkins Children’s Center reveals that the drug most commonly used in Type 2 diabetics who don’t need insulin works on a much more basic level than once thought, treating persistently elevated blood sugar — the hallmark of Type 2 diabetes — by regulating the genes that control its production. investigators say they have zeroed in on a specific segment of a protein called CBP made by the genetic switches involved in overproduction of glucose by the liver that could present new targets for drug therapy of the disease. In healthy people, the liver produces glucose during fasting to maintain normal levels of cell energy production. After people eat, the pancreas releases insulin, the hormone responsible for glucose absorption. Once insulin is released, the liver should turn down or turn off its glucose production, but in people with Type 2 diabetes, the liver fails to sense insulin and continues to make glucose. The condition, known as insulin resistance, is caused by a glitch in the communication between liver and pancreas. Metformin, introduced as frontline therapy for uncomplicated Type 2 diabetes in the 1950s, up until now was believed to work by making the liver more sensitive to insulin. The Hopkins study shows, however, that metformin bypasses the stumbling block in communication and works directly in the liver cells. Senior investigator, Fred Wondisford, M.D., who heads the metabolism division at Hopkins Children’s, tells us that, "Rather than an interpreter of insulin-liver communication, metformin takes over as the messenger itself Continue reading >>

Metformin For Gestational Diabetes - What It Is And How It Works

Metformin For Gestational Diabetes - What It Is And How It Works

In the UK it is common to use Metformin for gestational diabetes where dietary and lifestyle changes are not enough to lower and stabilise blood sugar levels. It is widely used to help lower fasting blood sugar levels as well as post meal levels. Metformin is an oral medication in tablet form. It is used in diabetics to help the body use insulin better by increasing how well the insulin works. In pregnancy it can be used in women who have diabetes before becoming pregnant (Type 2 diabetes) and in women who develop diabetes during pregnancy (gestational diabetes). Metformin is also used for other conditions too, commonly used in those that have PCOS (polycystic ovarian syndrome). Metformin is a slow release medication. Here are the most commonly asked Q&A on Metformin for gestational diabetes from our Facebook support group Why do I need to take Metformin? For many ladies with gestational or type 2 diabetes, if lower blood sugar levels cannot be reached through diet and exercise then medication will be required to assist. If blood sugar levels remain high, then the diabetes is not controlled and can cause major complications with the pregnancy and baby. Some consultants will prescribe Metformin on diagnosis of gestational diabetes on the basis of your GTT results. Others will let you try diet control first and when blood glucose levels rise out of target range, or close to the target range, they may prescribe Metformin as a way to help lower and control your levels. NICE guidelines regarding the timing and use of Metformin for gestational diabetes 1.2.19 Offer a trial of changes in diet and exercise to women with gestational diabetes who have a fasting plasma glucose level below 7 mmol/litre at diagnosis. [new 2015] 1.2.20 Offer metformin[4] to women with gestational dia Continue reading >>

Metformin Forever

Metformin Forever

**Metformin controls the insulin resistance of people who have type 2 diabetes so well that, if possible, all of us should be taking it. That’s what Roderic Crist, M.D., told me at the annual convention of the American Society of Bariatric Physicians in Denver this weekend. Dr. Crist specializes in family medicine in Cape Girardeau, Missouri. "Not everybody can take every drug," he added, when I followed up our conversation by calling him at his office after he returned home. "But most of the time people can take metformin if they take it carefully." Doctors increasingly prescribe it not only for type 2 diabetes but also for insulin resistance, polycystic ovary syndrome, and non-alcoholic fatty liver disease. Roughly one-third of Dr. Crist’s patients have diabetes. Well over half, if not two-thirds of the people he sees are insulin resistant. "I treat insulin resistance with that drug even if they aren’t fully diabetic." he says. "If they have high triglyceride levels and low HDL levels, particularly if they are centrally obese, they should probably be on metformin. It helps slow the progression of the disease from one thing to the next." But he goes further. He prescribes metformin to almost all of his patients who have type 2 diabetes – no matter how low their A1C level is. And he tells his patients that their levels should be 5.0 or less – not the American Diabetes Association’s less stringent recommendation of 7.0 or less. "If their A1C is at 5, their diabetes is in complete remission. So I have that as a goal." And he still prescribes metformin to them after they reach that goal. "The two important issues are that it will prevent progression and it should be used in the earliest phases of insulin resistance. We vastly underutilize metformin." But he has Continue reading >>

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