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Metformin Resistance Over Time

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 >>

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 >>

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 >>

Metformin May Minimize Multidrug Resistance In Cancer Cells

Metformin May Minimize Multidrug Resistance In Cancer Cells

Previous studies have shown that metformin, a drug commonly used to treat Type 2 diabetes, seems to also inhibit growth of multiple types of cancer cells. Moreover, studies on cancer patients who already take metformin to treat diabetes have hinted that the drug may boost their survival and prevent the emergence of new tumors. In a new PLOS ONE study, researchers probed the effects of metformin on the breast cancer cell line MCF7, which is commonly used for preclinical laboratory cancer research. They found that metformin may counteract drug resistance in cancer cells. Terra Arnason, a clinical endocrinologist from the University of Saskatchewan and a lead researcher on the study, told me more about what they found. What drew you to cell biology research, specifically studying cancer cells? TA: There is such an important potential societal impact to be made from advances in cancer research. Our team realized that there was a large population of cancer survivors who beat it once, only to have it come back years or decades later, without warning and without targeted therapy. Treatments then have to switch to less tolerable choices that have severe side effects and may not even be effective. Understanding the underpinnings of the cellular changes that cause this recurrence felt like an important area to study. Metformin is typically prescribed to treat Type 2 diabetes. Why did you think that metformin might inhibit cancer cells that are resistant to multiple drugs? TA: As a clinical endocrinologist, I use metformin to treat diabetes independently of cancer, but it was several large meta-analysis reports that led us down this path; people with Type 2 diabetes taking metformin were found to have lower rates of cancer, and were also found to do better with the cancers they ha 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 >>

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 >>

The Multiple Benefits Of Metformin

The Multiple Benefits Of Metformin

Metformin (brand name "Glucophage") has been used in the treatment of type II diabetes for the past 40 years.1 This drug counteracts many of the underlying factors that result in the manifestation of this insidious disease. Metformin also produces helpful side benefits that can protect against the lethal complications of type II diabetes. Frequently prescribed anti-diabetic drugs fail to address the fundamental causes of type II diabetes and can induce serious side effects. Type II diabetes affects between 16 to 19 million Americans. About 75% of type II diabetics will die from a cardiovascular-related disease. Conventional doctors often prescribe drugs for the purpose of lowering blood sugar levels. These drugs do not adequately address the multiple underlying pathologies associated with the type II diabetic state. Type II diabetes is characterized by cellular insulin resistence. The result is excess accumulation of glucose in the bloodstream as cells become resistant to the effects of insulin. Type II diabetes is characterized by cellular insulin resistence. The result is excess accumulation of glucose in the bloodstream because cells become resistant to the effects of insulin and fail to take up glucose As the type II diabetic condition progresses, many people gain weight and develop more fat cells.2 Treating type II diabetes with insulin-enhancing therapy increases the risk of cardiovascular complications, induces weight gain, and fails to correct the underlying cause of the disease. Many type II diabetics produce too much insulin in a futile attempt to drive glucose into insulin-resistant cells. When doctors prescribe insulin-enhancing drugs to these type II diabetics, a temporarily reduction of serum glucose may occur, but the long-term effects of this excess insu 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 >>

Metformin

Metformin

Two drugs from the biguanide class, metformin and phenformin, were developed in 1957. Unfortunately, phenformin reached the U.S. market first and resulted in several deaths from lactic acidosis. When this risk surfaced, phenformin was pulled from drugstore shelves worldwide. Metformin was eventually found to be 20 times less likely to cause lactic acidosis, but it was tainted by the history of its cousin. Metformin first became available in France in 1979 and has been widely used in Europe since then, but it was not cleared for use in Type 2 diabetes in the U.S. until 1994. Metformin Target Organ: Liver, secondary effects on muscle and fat. Action: Lower glucose production by liver, increase number of insulin receptors on muscle and fat cells Lowers HbA1c by 1.5% to 2.0% Time to reach maximum effect: 2-4 hrs Taken: with meal Drug Acts Over Dose Range Doses/Day Glucophage (metformin) 8-12 hrs 500 - 2550 mg 2-3 Glucophage XR (metformin) 24 hrs 500 - 2250 mg 1 Glucovance (metformin + glyburide) 12-18 hrs 250/1.25 to 2000/20 mg 2-3 Side Effects: bloating, fullness, nausea, cramping, diarrhea, vit B12 deficiency, headache, metallic taste, agitation, lactic acidosis Contraindications: DKA, alcoholism, binge drinking, kidney or liver disease, congestive heart failure, pregnancy, use of contrast media, surgery, heart attack, age > 80 Metformin is a chemical kin to the French lilac plant, which was noted in the early 1900’s to lower the blood sugar. However, French lilac, like phenformin, turned out to be too toxic for use in humans. Metformin, with a much shorter action time than phenformin, has a much lower risk for severe side effects and is quite safe for use by anyone who is otherwise healthy. In fact, in the major UKPDS study, it was the only drug that reduced diabetes-r Continue reading >>

Why Is Metformin Considered The Drug Of Choice For Type 2 Diabetes?

Why Is Metformin Considered The Drug Of Choice For Type 2 Diabetes?

Gunda Siska, PharmD, has worked in various fields within the pharmaceutical industry as a licensed pharmacist for more than 20 years. She is currently a staff hospital pharmacist assisting nurses and doctors with drug prescribing, administration, and dispensing, as well as independently monitoring and dosing highly toxic and dangerous drugs. For 2 years, she was concurrently a consultant pharmacist for skilled nursing facilities and nursing homes. Dr. Siska is a member of the New Mexico Society of Health-System Pharmacists and the American Academy of Anti-Aging Medicine. Follow her on Twitter @GundaSiska Metformin is a medication that I believe is underappreciated by the general public. Many people ttell me that their doctor prescribed this drug for them, but they took themselves off of it, but if they knew what I know about metformin, they would have stayed on the medication. This is what I know: metformin extends life. It’s been proven in animal studies1 and in humans. A prospective observational study of nearly 20,000 people with type 2 diabetes mellitus (T2DM) and arteriosclerosis found that metformin use was associated with 24% lower all-cause mortality compared to patients who were not taking metformin.2 It is also the number one go-to medication for type 2 diabetes for several years, despite all the new designer medications coming on the market trying to replace it. How does metformin save lives? Mainly through cardioprotection. Metformin reduces cardiovascular risk in humans.3 Most people with T2DM will most likely die from a cardiovascular event, especially if they are not on metformin.4,5,6 Metformin has so many positive effects on the body, no one really knows for sure all the ways it preserves life. It produces modest weight loss in the near term5 and blun Continue reading >>

Pcos: Insulin And Metformin

Pcos: Insulin And Metformin

Young women with PCOS often have elevated insulin levels and are more likely to develop diabetes. Metformin is a medication often prescribed for women with PCOS to help prevent diabetes. A lifestyle that includes healthy nutrition and daily exercise is the most important part of a PCOS treatment plan. What is insulin? Insulin is a hormone made by an organ in the body called the pancreas. The food you eat is broken down into simple sugar (glucose) during digestion. Glucose is absorbed into the blood after you eat. Insulin helps glucose enter the cells of the body to be used as energy. If there’s not enough insulin in the body, or if the body can’t use the insulin, sugar levels in the blood become higher. What is insulin resistance? If your body is resistant to insulin, it means you need high levels of insulin to keep your blood sugar normal. Certain medical conditions such as being overweight or having PCOS can cause insulin resistance. Insulin resistance tends to run in families. What can insulin resistance do to me? High insulin levels can cause thickening and darkening of the skin (acanthosis nigricans) on the back of the neck, axilla (under the arms), and groin area. In young women with PCOS, high insulin levels can cause the ovaries to make more androgen hormones such as testosterone. This can cause increased body hair, acne, and irregular or few periods. Having insulin resistance can increase your risk of developing diabetes. How can I lower my insulin levels? You can help lower your insulin levels naturally by eating fewer starches and sugars, and more foods that are high in fiber and low in refined carbohydrates. Low glycemic foods, on the other hand, don’t raise your blood sugar or insulin levels as much as foods that are high in sugar or refined carbohydr Continue reading >>

Original Article Addition Of Metformin To A Lifestyle Modification Program In Adolescents With Insulin Resistance

Original Article Addition Of Metformin To A Lifestyle Modification Program In Adolescents With Insulin Resistance

To evaluate whether metformin, when added to a program of personal goal setting, improves weight loss and clinical status in obese adolescents. In a randomized double-blind placebo controlled trial, 85 adolescents with insulin resistance were randomized to receive metformin (70%) or placebo (30%), along with monthly goal setting for diet and exercise modification. Anthropometric measures, fasting blood analysis, and glucose tolerance tests were performed at baseline and 6 months. Results Mean age was 15.7 years. Mean body mass index (BMI) was 39.7 kg/m2. 71% were female, 58% were Hispanic, and 34% were African-American. 76% of participants completed the study. Goal setting alone did not result in significant weight loss. In addition, there were no group differences between metformin and placebo in weight loss or measures of glucose metabolism. However, among females taking metformin, there was a significant decrease in BMI not seen in the placebo group. Furthermore, metformin adherence, when accompanied by lifestyle change, was a predictor of BMI decrease of 5% or more. 60% of 10 subjects who adhered to metformin and decreased portion size decreased BMI by >5%. Conclusions In this group of predominately minority adolescents, monthly goal setting alone did not lead to weight loss. Although the addition of metformin had no effect on weight loss overall, the agent did significantly increase weight loss among females and weight loss was predicted by degree of metformin adherence. However, weight loss was only found in those participants also reporting lifestyle change, particularly a decrease in portion sizes. These results suggest that metformin may be a useful agent to promote short-term weight loss among girls making modest lifestyle changes. Continue reading >>

Therapeutic Use Of Metformin In Prediabetes And Diabetes Prevention

Therapeutic Use Of Metformin In Prediabetes And Diabetes Prevention

People with elevated, non-diabetic, levels of blood glucose are at risk of progressing to clinical type 2 diabetes and are commonly termed ‘prediabetic’. The term prediabetes usually refers to high–normal fasting plasma glucose (impaired fasting glucose) and/or plasma glucose 2 h following a 75 g oral glucose tolerance test (impaired glucose tolerance). Current US guidelines consider high–normal HbA1c to also represent a prediabetic state. Individuals with prediabetic levels of dysglycaemia are already at elevated risk of damage to the microvasculature and macrovasculature, resembling the long-term complications of diabetes. Halting or reversing the progressive decline in insulin sensitivity and β-cell function holds the key to achieving prevention of type 2 diabetes in at-risk subjects. Lifestyle interventions aimed at inducing weight loss, pharmacologic treatments (metformin, thiazolidinediones, acarbose, basal insulin and drugs for weight loss) and bariatric surgery have all been shown to reduce the risk of progression to type 2 diabetes in prediabetic subjects. However, lifestyle interventions are difficult for patients to maintain and the weight loss achieved tends to be regained over time. Metformin enhances the action of insulin in liver and skeletal muscle, and its efficacy for delaying or preventing the onset of diabetes has been proven in large, well-designed, randomised trials, such as the Diabetes Prevention Program and other studies. Decades of clinical use have demonstrated that metformin is generally well-tolerated and safe. We have reviewed in detail the evidence base supporting the therapeutic use of metformin for diabetes prevention. Notes Ulrike Hostalek and Steven Hildemann are employees of Merck KGaA, a pharmaceutical sponsor of several for Continue reading >>

Insulin Resistance And Weight Loss With Metformin

Insulin Resistance And Weight Loss With Metformin

The cells in your body can’t absorb glucose, the body’s primary source of energy, without insulin. When glucose enters the bloodstream, the pancreas releases insulin. If cells become insulin-resistant, they no longer respond to insulin release by absorbing glucose. More glucose stays in the bloodstream, a condition known as hyperglycemia. Once this happens, a person is diagnosed with type 2 diabetes, formerly called adult-onset diabetes. Metformin is a medication that can improve the cells' sensitivity to insulin; weight loss may occur, as well. Video of the Day Insulin resistance occurs most often in people who have a family history of the disorder, overweight people and women who have polycystic ovary disease, a hormonal disorder characterized by insulin resistance and an over-production of male hormones called androgens. Inactivity also contributes to insulin resistance. Insulin resistance may have no obvious symptoms outside of weight gain. Metabolic syndrome, a disorder that includes insulin resistance and borderline high glucose levels, also includes excess weight around the waist, high blood pressure and abnormal cholesterol levels. Weight Gain and Insulin Resistance People with insulin resistance often gain weight. When blood sugar goes up, the pancreas release insulin. If cells don’t absorb glucose, the pancreas releases ever larger amounts of insulin in an effort to “force” cells to absorb the glucose. Eventually, insulin levels remain higher than normal in the bloodstream. Since high insulin levels increase hunger, people with high insulin levels often gain weight. Drugs like metformin that lower insulin can result in weight loss. Metformin attaches to the surfaces of cells and increases their ability to take in glucose. The drug also reduces glucos Continue reading >>

Insulin Resistance And The Use Of Metformin: Effects On Body Weight

Insulin Resistance And The Use Of Metformin: Effects On Body Weight

by Ruchi Mathur, MD, FRCPC Dr. Mathur is Assistant Professor of Medicine, Cedars Sinai Medical Center, University of California, Los Angeles, California. Bariatric Times. 2011;8(1):10–12 Abstract Metformin is a widely perscribed drug for the treatment of diabetes and is often used off label for the treatment of prediabetes and insulin resistance. In addition to its primary use, metformin has often been cited as having weight loss benefits. This article reviews the concept of insulin resistance as it pertains to body weight and the effects of meformin on body weight in subgroups of patients with and without diabetes. Introduction Insulin is an anabolic storage hormone produced by the beta cells in both a basal and a pulsatile fashion in response to food intake. Insulin is fundamental in allowing cells to uptake and use glucose. Insulin also regulates gluconeogenesis along with processes, such as protein synthesis and lipogenesis. When we were evolving, the theory is that insulin was necessary because we lived a life of feast and famine. Those who could store calories had a survival benefit, thus insulin had a significant evolutionary role. So, where and when did insulin become a bad thing? Likely, at the same time our evolutionary environment took a bit of a turn. These days, it is usual to go three hours without eating, and certainly not three days! Thus, what was once adaptive is now maladaptive as we continue to store as our ancestors did. Our environment has changed faster than our genetics. Insulin resistance is an impaired response to endogenous or exogenous insulin in cells, tissues (especially skeletal muscle and adipose tissue), the liver, or the whole body.[1,2] Many investigators believe that insulin resistance is an important factor in the development of th Continue reading >>

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