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 >>
Ask The Experts - How Does Metformin Affect Insulin Resistance?
How Does Metformin Affect Insulin Resistance? What is the role of metformin in managing insulin resistance and obesity in people with diabetes? How does metformin affect the obese nondiabetic patient? Response from Mary Anne Dumas, PhD, RN, CFNP, FAANP In order to understand the role of metformin in insulin resistance and obesity, it is essential to understand the pathophysiology of both clinical problems and the pharmacologic mechanisms of metformin. Insulin resistance occurs when there is an impairment of insulin transport at either the prereceptor, receptor, or postreceptor sites. Insulin resistance occurs in obese individuals, usually at the postreceptor site, where there is an apparent failure to activate the postreceptor tyrosine kinase.[ 1 ] (Type II diabetes reportedly is related to a postreceptor abnormality.[ 1 ]) Failure of the cellular transport of insulin results in hyperglycemia, requiring greater amounts of insulin to maintain euglycemia (normal level of sugar in the blood). Euglycemia may be maintained for a long period by hyperinsulinemia; however, insulin levels are not able to sustain control glucose levels, and hyperglycemia results.[ 1 , 2 ] Metformin is a biguanide (a hypoglycemia-inducing drug) that has been demonstrated to decrease hepatic glucose production and improve peripheral insulin sensitivity. Metformin benefits individuals with diabetes by: Reducing lipid levels (eg, triglycerides); Facilitating postreceptor transport of insulin; and Continue reading >>
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 >>
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 >>
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 me Continue reading >>
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 >>
Metformin Improves Glucose Effectiveness, Not Insulin Sensitivity: Predicting Treatment Response In Women With Polycystic Ovary Syndrome In An Open-label, Interventional Study
Metformin Improves Glucose Effectiveness, Not Insulin Sensitivity: Predicting Treatment Response in Women With Polycystic Ovary Syndrome in an Open-Label, Interventional Study We are experimenting with display styles that make it easier to read articles in PMC. The ePub format uses eBook readers, which have several "ease of reading" features already built in. The ePub format is best viewed in the iBooks reader. You may notice problems with the display of certain parts of an article in other eReaders. Generating an ePub file may take a long time, please be patient. Metformin Improves Glucose Effectiveness, Not Insulin Sensitivity: Predicting Treatment Response in Women With Polycystic Ovary Syndrome in an Open-Label, Interventional Study Cindy T. Pau, Candace Keefe, [...], and Corrine K. Welt Although metformin is widely used to improve insulin resistance in women with polycystic ovary syndrome (PCOS), its mechanism of action is complex, with inconsistent effects on insulin sensitivity and variability in treatment response. The aim of the study was to delineate the effect of metformin on glucose and insulin parameters, determine additional treatment outcomes, and predict patients with PCOS who will respond to treatment. We conducted an open-label, interventional study at an academic medical center. Women with PCOS (n = 36) diagnosed by the National Institutes of Health criteria participated in the study. Subjects underwent fasting blood sampling, an IV glucose tolerance test, dual-energy x-ray absorptiometry scan, transvaginal ultrasound, and measurement of human chorionic gonadotropin-stimulated androgen levels before and after 12 weeks of treatment with metformin extended release 1500 mg/d. Interval visits were performed to monitor anthropometric measurements and mens Continue reading >>
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 >>
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 >>
Prediabetes & Insulin Resistance
What is insulin? Insulin is a hormone made in the pancreas, an organ located behind the stomach. The pancreas contains clusters of cells called islets. Beta cells within the islets make insulin and release it into the blood. Insulin plays a major role in metabolism—the way the body uses digested food for energy. The digestive tract breaks down carbohydrates—sugars and starches found in many foods—into glucose. Glucose is a form of sugar that enters the bloodstream. With the help of insulin, cells throughout the body absorb glucose and use it for energy. Insulin's Role in Blood Glucose Control When blood glucose levels rise after a meal, the pancreas releases insulin into the blood. Insulin and glucose then travel in the blood to cells throughout the body. Insulin helps muscle, fat, and liver cells absorb glucose from the bloodstream, lowering blood glucose levels. Insulin stimulates the liver and muscle tissue to store excess glucose. The stored form of glucose is called glycogen. Insulin also lowers blood glucose levels by reducing glucose production in the liver. In a healthy person, these functions allow blood glucose and insulin levels to remain in the normal range. What happens with insulin resistance? In insulin resistance, muscle, fat, and liver cells do not respond properly to insulin and thus cannot easily absorb glucose from the bloodstream. As a result, the body needs higher levels of insulin to help glucose enter cells. The beta cells in the pancreas try to keep up with this increased demand for insulin by producing more. As long as the beta cells are able to produce enough insulin to overcome the insulin resistance, blood glucose levels stay in the healthy range. Over time, insulin resistance can lead to type 2 diabetes and prediabetes because the bet 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 1Department of Pediatrics, St Antonius Hospital, Nieuwegein, The Netherlands 2Department of Clinical Pharmacy, St Antonius Hospital, Nieuwegein, The Netherlands 3Department of Pediatrics, Jeroen Bosch Hospital, s-Hertogenbosch, The Netherlands 1Department of Pediatrics, St Antonius Hospital, Nieuwegein, The Netherlands 1Department of Pediatrics, St Antonius Hospital, Nieuwegein, The Netherlands 2Department of Clinical Pharmacy, St Antonius Hospital, Nieuwegein, The Netherlands 3Department of Pediatrics, Jeroen Bosch Hospital, s-Hertogenbosch, The Netherlands *Department of Pediatrics, St Antonius Hospital, PO Box 2500, 3430 EM Nieuwegein, The Netherlands. E-mail: [email protected] Received 2016 Jun 30; Accepted 2016 Jul 5. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit This article has been cited by other articles in PMC. 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 1016 years old wit Continue reading >>
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 >>
The Addition Of Metformin In Type 1 Diabetes Improves Insulin Sensitivity,diabetic Control, Body Composition And Patient Well-being.
1. Diabetes Obes Metab. 2007 Jan;9(1):143-5. The addition of metformin in type 1 diabetes improves insulin sensitivity,diabetic control, body composition and patient well-being. AIM: As many overweight people with T1DM are insulin resistant, adjuvant therapy with insulin sensitising agents, such as metformin, may be beneficial. This studyevaluated the effect of adjuvant metformin in T1DM on insulin sensitivity,diabetic control, body composition, quality of life (QOL) and treatmentsatisfaction.MATERIALS AND METHODS: A 3-month prospective open-labelled pilot study of 16patients aged 18-40 with T1DM and body mass index (BMI) >25 kg/m(2) wasperformed. The patients received 500-850 mg metformin twice daily. Insulinsensitivity, assessed by a frequently sampled intravenous glucose tolerance test [n=5], body composition, HbA(1c) and quality of life (QOL) were measured beforeand after treatment. A retrospective review of 30 patients with T1DM treated withmetformin for at least 4 months was also performed. BMI, HbA(1c) and insulinrequirements during metformin treatment was compared to pre-metformin data, andto patients treated with insulin only.RESULTS: In the pilot study, insulin sensitivity increased significantly from0.86 +/- 0.33 x 10(-4)/min/(microU/ml) to 1.17 +/- 0.48 x 10(-4)/min/(microU/ml) after 3 months adjuvant therapy (p = 0.043). This was associated with a decreasedinsulin requirement and mean daily blood glucose. There were no significantchanges in HbA(1c) or body composition. QOL significantly improved (p < 0.002).The retrospective review revealed an initial reduction in HbA(1c) (0.8 +/- 1.4%, p = 0.001). This effect diminished with prolonged treatment. BMI decreased inpatients remaining on metformin for a 2-year period (0.5 +/- 0.5kg/m(2), p =0.042).CONCLUSION: Continue reading >>
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 >>
Reducing Insulin Resistance With Metformin: The Evidence Today.
Abstract Insulin resistance, defined as the inability of insulin to exert a normal biological action at the level of its target tissues, is one of the principal pathogenetic defects of type 2 diabetes. Metformin, the most widely-prescribed insulin-sensitizing agent in current clinical use, improves blood glucose control mainly by improving insulin-mediated suppression of hepatic glucose production, and by enhancing insulin-stimulated glucose disposal in skeletal muscle. Experimental studies show that metformin-mediated improvements in insulin sensitivity may be associated with several mechanisms, including increased insulin receptor tyrosine kinase activity, enhanced glycogen synthesis, and an increase in the recruitment and activity of GLUT4 glucose transporters. In adipose tissue, metformin promotes the re-esterification of free fatty acids and inhibits lipolysis, which may indirectly improve insulin sensitivity through reduced lipotoxicity. The improved glycaemia with metformin is not associated with increased circulating levels of insulin, and the risk of hypoglycaemia with metformin is minimal. The therapeutic profile of metformin supports its use for the control of blood glucose, in diabetic patients and for the prevention of diabetes in subjects with impaired glucose tolerance. Moreover, the improvement by metformin of cardiovascular risk factors associated with the dysmetabolic syndrome may account for the significant improvements in macrovascular outcomes observed in the UK Prospective Diabetes Study. Continue reading >>