Exenatide
Authors: Anne Peters, MD, CDE, FACP Faculty and Disclosures Last year at the American Diabetes Association (ADA) Scientific Sessions, the drug exenatide had just been approved for use by the US Food and Drug Administration (FDA). Many healthcare providers attending the meeting had never used this medication, although they were excited about its potential. At this year's ADA meeting, with 1 year of experience accrued, the information presented included data on currently off-label drug combinations with exenatide, such as thiazolidinediones (TZDs) and insulin, and further follow-up of the initial phase 3 study cohort. In addition, the potential of exenatide to help with islet cell function, including use in patients with type 1 diabetes undergoing islet cell transplantation, was explored. Incretins are hormones produced from the gastrointestinal track that act to enhance the normal release of insulin after the oral ingestion of carbohydrates. [1,2] They also slow the gastric absorption of nutrients and act to promote a feeling of satiety that can lead to weight loss in overweight individuals. The most well-characterized incretin is glucagon-like peptide-1 (GLP)-1. Exenatide, the currently available incretin mimetic, was discovered in the saliva of the Gila monster. It has over 50% homology with native human GLP-1 and many of the same biological effects, except that it has a much longer half-life (10 hours vs just a few minutes). Because it mimics the activities of GLP-1, it lowers postprandial glucose levels in a glucose-dependent fashion without causing hypoglycemia, unless used with another drug that can cause hypoglycemia, such as an insulin secretagogue or insulin. It also reduces postprandial glucagon levels, which are paradoxically elevated in patients with type 2 Continue reading >>
Metformin, The Anti-aging Miracle Drug
Metformin, The Anti-Aging Miracle Drug Diabetes Drugs Take A BAD RAP This article is part two of a series, for part one, click here. You probably think of Diabetes Drugs as all lumped together as “Bad Drugs”. For many years , I certainly did. Perhaps it was the Avandia story that gave Diabetes Drugs a Bad Rap and made us think poorly of ALL Diabetes Drugs. Upper Left Image: Photo of French Lilac Plant , the plant origin of Metformin, courtesy of Wikimedia Commons. Avandia, the “BAD Drug” for Diabetes Take the case of Avandia, approved in 1999, it quickly became the world’s best selling diabetes drug. However, 8 years later, the New England Journal reported that Avandia causes increased heart attack rates, and sales were suspended in Europe.(1A) In November 2011, GlaxoSmithKline admitted they withheld safety data on Avandia and agreed to pay the US government 3 billion in civil and criminal penalties related to illegal marketing. The Avandia case gave all diabetes drugs a “Bad Rap”. The reality is that there is one diabetes drug that has stood the test of time, and is in fact a “Good Drug”. This is Metformin. Perhaps the plant origin of the drug makes it a “good drug”. Metformin, the “Good Drug” Is There Anyone Who Should not Take It ? At the May 2012 Orlando A4M Meeting, Terry Grossman, M.D. from Golden Colorado gave an excellent presentation on Metformin. Credit and thanks goes to Terry Grossman MD for sharing his talk at the meeting with all of us. Much of this article comes from Grossman’s PowerPoint slides. Dr Terry Grossman is co-author of the Ray Kurzweil book, Fantastic Voyage. Upper Left Image : Photo of Terry Grossman MD, courtesy of Terry Grossman MD. Metformin by Terry Grossman MD- Metformin Discovery and Approval Discovered in the Continue reading >>
10 Surprising Uses And Benefits Of Metformin, Including Side Effects/risks
Metformin is a prescription drug that successfully lowers blood sugar levels in type 2 diabetes patients. Metformin has many other (sometimes unknown) benefits, such as its use in cancer and polycystic ovarian syndrome (PCOS) treatment. However, metformin also has several adverse side effects and should be taken with precaution. Positive Effects of Metformin Currently, metformin is used not only as a first-line drug treatment for type 2 diabetes, but also for insulin resistance, PCOS, and even cancer. Metformin adjusts cellular energy consumption by targeting the liver, preventing it from creating more sugar, and inhibiting a hormone (glucagon) responsible for increasing blood sugar levels [R]. The effect of metformin on blood sugar levels can be attributed to AMPK, an enzyme that controls the production and storage of energy in cells by indicating that muscle cells should increase sugar absorption from the blood [R]. In a review of over 300,000 people, it was found that metformin may also reduce the risk of cancer in patients with type 2 diabetes through a known tumor suppressant (LKB1), which activates AMPK [R]. Recently, attention has shifted to non-AMPK mechanisms, often involving mitochondria, the parts of cells responsible for energy production [R]. Type 2 diabetes coexists with insulin resistance and patients develop extremely high blood sugar levels. Metformin lowers blood sugar, preventing permanent organ damage, which could eventually lead to dysfunction and failure [R, R]. Metformin exerts its effects through AMPK, which initiates the absorption of sugar from the blood into the muscles. It has been shown that metformin increases AMPK, which would imply pulling more sugar from the blood into the tissue and lowering blood sugar concentrations [R]. On the other Continue reading >>
Metformin And Weight Loss: Does It Work And Should You Be Taking It?
Created for Greatist by the experts at Healthline. Read more Youre in a fitting room working through the assortment of jeans you brought in. Youve got the size you think you are, the size you probably are (reality check), and the size you hope to be soon, if you can just make it there! Then you hear about a drug called metformin that may aid in weight loss. Sure, it might sound odd to consider taking a medication usually prescribed for type 2 diabetes just to lose some weight. But does it work, and is it a good option for you? Lets look at how metformin, a drug prescribed to manage blood sugar levels, has earned this reputation. Can metformin really help me lose weight? Metformin can help some people lose weight, but the reasons arent exactly clear. Some researchers believe the drug reduces appetite, while others theorize it changes the way the body stores and uses fat. But researchers agree that metformin is not a quick fix. According to one long-term study , weight loss from metformin happened gradually over one to two years. And the average amount of weight lost in that time ranged from 4 to 7 pounds. Lifestyle plays a big role as well. Taking the drug without practicing other healthy habits may not lead to weight loss. People who exercise and follow a healthy diet while taking metformin tend to lose the most weight. This is because metformin is thought to increase the number of calories burned during exercise. So if you arent exercising, you likely wont reap this benefit. Continued use is also important, as weight loss may last only as long as youre taking the medication. That means if you stop taking metformin, theres a good chance youll return to your original weight. And even while youre still taking the drug, you may slowly gain back any weight youve lost. Metf Continue reading >>
Widely Used Diabetes Drug May Hold Potential To Aid Long-term Weight Loss
This was an observational follow-up study from a randomised controlled trial (RCT) . RCTs are the best way to show which treatment works. However, in this case the RCT finished after a year, and the researchers are now following up on people who may no longer be taking the treatments set at the start of the trial but may have switched to other treatments or stopped treatment altogether. This is not surprising given the length of the study, but it makes the results less reliable. For the original trial, researchers randomly divided 3,234 people who were overweight or obese and at risk of diabetes into 3 groups: assigned to a strict diet and exercise plan assigned to take a placebo (pretend) drug People stayed in their groups for a year. At the end of the year, researchers looked at the participants' initial weight loss or gain, and whether they had developed type 2 diabetes. They then followed them up for another 14 years, with annual records of their weight. During the second year, everyone was offered the diet and exercise plan as it had shown most success in the first year. People on metformin were able to continue it if they wished. People who developed diabetes were treated by their local healthcare provider. For this study, researchers looked at the results of the 1,066 people who lost 5% of their weight in the first year, to see which factors from the start of the study predicted who was able to keep off at least 5% of their weight after 15 years. Factors examined included: blood sugar results at the start of the study In the first year, 28.5% of people taking metformin lost 5% of body weight, compared to 62.6% of people on a strict diet and exercise plan and 13.4% of people in the placebo group. Among those people who had lost 5% of body weight in the first year Continue reading >>
Metformin And Weight Loss: Here's Everything You Should Know Before Trying It
Maybe youve heard that the diabetes drug metformin makes people lose weight. But is that even true? And more important, might you be one of the people who could drop pounds by taking this prescription medication? Great questions. The answers are: Yes, metformin helps some people lose weight, but depending on whats going on with your body, you mayor may notbe one of them. Before we get to whether it makes sense for you to ask your doctor to take out her Rx pad, heres a little background: Metformin is an oral drug that is FDA approved to control blood sugar levels in people with type 2 diabetes . It is sometimes used off-label (meaning docs prescribe it for non-FDA-approved uses it seems to work for) in people with prediabetes i.e. they have somewhat high blood sugar or some insulin resistance, and so are at risk for developing diabetes . Its also prescribed off-label for other conditions, such as polycystic ovarian syndrome . Researchers arent 100% sure of all the ways the drug acts in the body. Metformin is a complex drug with multiple sites of action and multiple molecular mechanisms that are not fully understood, according to a 2017 report . What is known is that metformin causes the liver to lower the amount of glucose (sugar) it makes and releases into your bloodstream, and also affects your gut, so that you use glucose more efficiently. All of this helps people with diabetes, whose blood sugar is too high and/or not being used properly (which makes the body want to crank out more.) So how does it help some people lose weight? Folks seem to be less hungry on the drug. Metformin mainly causes weight loss by lowering food intake, says Steven K. Malin, Ph.D. , an assistant professor and expert in exercise metabolism and human nutrition at the University of Virginias C Continue reading >>
The Drug Virtually Everyone Should Ask Their Doctor About
With each passing year, fresh scientific evidence emerges to vindicate Life Extension®’s contention that aging humans can derive enormous benefit from an antidiabetic drug called metformin. In 2010 alone, scientists at top-ranked institutions made landmark discoveries that broaden its use to combat degenerative disease. The ability of metformin to help facilitate weight loss has long been known. What few doctors understand are the unique mechanisms by which metformin can prevent and even help treat certain cancers. In a remarkable finding, a team of Swiss researchers found that diabetic women on a long-term metformin regimen (5 years or more) experienced a 56% reduction in breast cancer risk!1 It also slashed pancreatic cancer rates by 62% in diabetics and may cut lung cancer rates in smokers.2,3 In this article, a novel link between impaired glucose control and cancer is detailed. You will discover the growing list of cancers metformin may effectively combat, including those of the colon, uterus, and prostate. You will also learn of a striking connection between the anti-cancer mechanisms of metformin and calorie restriction! Why Metformin Should Be Viewed Differently than Other Drugs Many Life Extension members like to brag that they do not need to take any prescription drugs. Given the lethal side effects posed by so many FDA-approved medications, avoiding them whenever possible makes sense. Metformin is an exception! Its broad-spectrum anti-aging properties make it a drug that most longevity enthusiasts should seriously consider asking their doctors about. Since it long ago came off patent, metformin is a super-low cost generic that everyone can afford. Metformin Was Originally a Botanical Compound Although it is sold as a prescription drug today, metformin has a Continue reading >>
Non-diabetic Uses Of Metformin
Although the U.S. Food and Drug Administration oversees the safety and effectiveness of drugs prescribed by American doctors, it does not regulate the practice of medicine. So, many medications are used “off-label,” meaning your doctor may prescribe a drug for purposes that have not yet been approved by the FDA. About 1/5 of the prescriptions for common medications are written for an off-label use, according to a 2012 review in “Mayo Clinic Proceedings.” Metformin (Glucophage), a drug licensed to treat type 2 diabetes, has a number of off-label uses. How Metformin Works Metformin is unlike other medications used to treat type 2 diabetes. Although all of its actions are not completely understood, metformin’s main mode of action is to decrease glucose production in your liver. In addition, metformin increases your cells’ sensitivity to the insulin released from your pancreas, which increases your body’s ability to metabolize glucose. Together, these actions reduce your blood glucose level without driving it too low. These same properties make the drug potentially useful in a number of situations. Drug-Induced Weight Gain Atypical antipsychotic medications, such as olanzapine (Zyprexa), are prescribed for managing schizophrenia, bipolar disorder and other conditions. But in many people, these medications cause significant weight gain, which is believed to stem from drug-induced appetite stimulation and insulin resistance. A March 2011 analysis in the “British Journal of Clinical Pharmacology” showed people who gain weight as a result of taking olanzapine may lose some of that weight by also taking metformin. This has important implications for people whose psychiatric conditions cannot be controlled without atypical antipsychotics. Metformin may not be ap Continue reading >>
Metformin – The World’s First True Anti-aging Drug
Metformin – The World’s First True Anti-Aging Drug Metformin is truly an amazing drug. It has potentially far-reaching effects on everything from diabetes, obesity, cancer, and heart disease to general life extension. Metformin, Insulin Sensitivity, and Fat Loss Next to aspirin, metformin, originally known as glucophage (“sugar eater”), is one of the oldest drugs in use. It was invented in 1959 and used freely in other countries, but the ever-cautious FDA didn’t approve it for use in the U.S. until 1995. The drug is currently used by type II diabetics the world over to help them handle dietary sugar or, more broadly, carbohydrates. However, when people who don’t have diabetes take metformin, it generally leads to fat loss because it also allows the non-diabetic person to handle carbs better. Bodybuilders have long been fans of the drug because it makes muscle cells more sensitive to insulin so that more nutrients can be shuttled towards muscle cells. While it’s doing its magic on muscle cells, metformin simultaneously de-sensitizes fat cells to insulin’s effect so fat cells can’t store nutrients as easily. As such, muscles get bigger and fat stores get smaller. Metformin and Cancer It seems that just about every chemical either causes cancer or helps prevent it, but a recent report involving metformin’s effects on cancer are truly noteworthy. In one of the largest studies of its kind, a group of scientists pored over the 10-year case histories of 8,000 type II diabetics who’d been using metformin.(1) They found that metformin users had an incredible 54% lower incidence of all cancers compared to the general population. Not only did the drug exhibit a preventative effect, but the metformin users who developed cancer had a much higher survival rate, Continue reading >>
New Weight Loss Formula: Popular Diabetes Drug Melts Pounds, Studies Show
If the FDA says yes, a major new weight loss drug may hit the market this year. A high-dose formulation of liraglutide, the popular diabetes drug from Novo Nordisk melts up to 10 percent of body mass, studies show. Liraglutide, available in 1.2 mg and 1.8 mg doses as Victoza, is already a huge success for Novo Nordisk. The company has now filed with the FDA seeking approval for a 3.0 mg dose after studies found major weight loss benefits (in conjunction with diet and exercise.) In clinical trials, liraglutide helped those taking it lose 5 to 10 percent of their body mass, according to research published in the International Journal of Obesity. And while this study looked at people with diabetes, a previous study published in the Lancet tested the drug in non-diabetics and found similarly impressive weight loss. In late December, Novo Nordisk filed two submissions for liraglutide, a new drug application (NDA) with the FDA, and a Marketing Authorization Application (MAA) with the European Medicines Agency, according to Drug Discovery & Development. But some folks may not have to wait even that long. In February, Novo Nordisk made the unusual move of targeting Mexico for an initial approval of high-dose liraglutide. And others may not wait at all; while the studies warn against using liraglutide "off-label" for weight loss, it seems certain that patients will seek to use Victoza for that purpose. Liraglutide works by mimicking a hormone known as GLP-1, which slows digestion and stimulates the body's natural production of insulin. Victoza has been very successful for Novo Nordisk, with sales jumping 58 percent in 2012, and climbing an additional 14 percent in the third quarter of 2013. Experts are projecting that liraglutide would have blockbuster potential as a weight loss Continue reading >>
What Health Problems Besides Diabetes May Be Treated With Metformin?
Insulin resistance is one of the key factors leading to diabetes, but it is increasingly recognized as an important issue in other settings as well. Insulin resistance itself increases the risk of cardiovascular disease, and most physicians now consider pre-diabetes to be a serious condition, not only because of the likely progression to diabetes but also because heart disease risk is higher in people with blood sugars in the pre-diabetic range than in those with normal blood sugar levels. Many physicians and diabetes researchers think it's appropriate to treat people with pre-diabetes with metformin, and some even advocate the use of metformin in a person with abdominal obesity, even if he or she has normal blood sugar levels. In addition, polycystic ovary syndrome (PCOS) is often treated with metformin. PCOS is a metabolic disorder that affects women of childbearing age. The symptoms include irregular periods and infertility, as well as excessive facial and body hair, acne, and hair loss from the scalp. PCOS is a complex disorder and not fully understood, but a major part of its cause appears to be insulin resistance. A high percentage of women with PCOS are also overweight. Metformin treatment sometimes helps with weight loss, often corrects irregular menstrual periods, and definitely improves fertility. In fact, because PCOS is one of the most common causes of infertility, metformin, a medication thought of as a diabetes drug, is also one of the most widely used infertility treatments. It's important to emphasize that all uses of metformin other than the treatment of diabetes are "off label." That is, the Food and Drug Administration (FDA) has not approved metformin for use in these areas, but it is often of benefit and physicians frequently prescribe it for these p Continue reading >>
Weight Loss Through The Use Of Off-label Medicine
If you have type one diabetes , and youre struggling to lose or even maintain weight, youre not alone. Studies show that people with diabetes lack the hormone amylin , thats responsible for hunger and fullness cues, and the longer someone is on synthetic insulin, the more insulin resistant they become. This can wreak havoc on ones metabolism, and frankly, sanity. But researchers and doctors are finding success with prescribing the off label use of SGLT-2 inhibitors (typically used for type 2 patients) for their type 1 patients, with increased insulin sensitivity , lower HbA1cs, and weight loss as a result. A win-win? Lets dig into the research and find out: Discovered in the 1980s , National Institutes of Health (NIH) researchers first harnessed the power of the kidneys to support blood sugar regulation. Sodiumglucose cotransporter (SGLT2) inhibitors are a prescription drug, and according to the Food and Drug Administration (FDA) , are a class of prescription medicines that are FDA-approved for use with diet and exercise to lower blood sugar in adults with type 2 diabetes . SGLT2 inhibitors lower blood sugar by causing the kidneys to remove sugar from the body through the urine. The safety and efficacy of SGLT2 inhibitors have not been established in patients with type 1 diabetes, and the FDA has not approved them for use in these patients. These drugs are typically administered once daily, orally. While not approved by the FDA for type 1 diabetes, off-label use of SGLT2 inhibitors continues to rise. Research has shown positive patient outcomes , including reductions in HbA1c, body weight, fasting glucose, blood pressure, and lower insulin doses, along with improvements in quality of life, like reduction in postprandial blood sugar spikes . Research also has shown an i Continue reading >>
Weight Loss Medications
IF AT FIRST YOU DON’T SUCCEED… Obesity is a biological and treatable disease. The question everyone should ask is “what is the risk to my health from not treating obesity?” And then one should ask, “what is the benefit and risk of using medications to treat obesity?” To understand the use of medications to treat obesity, let’s review their history. The use of drugs for weight loss is as old as medical practice. From as long ago as 2000 BC, Indian remedies known as ayurvedic [eye-yer-VAY-dik] herbs were used for weight loss. These herbs included cayenne pepper, licorice root and cinnamon. In the US, medications have been used to help people lose weight. Unfortunately, several obstacles have confronted those who used these drugs in the past. Thyroid extract was introduced in the late 1800s. To achieve effective weight loss it had to cause hyperthyroidism. In the 1930s, dinitrophenol [die-nigh-troh-FEE-null], a then popular drug, was one of the first drugs that carried FDA warnings and became restricted. Dinitrophenol use was associated with cataracts, blood disorders and death. Later, rainbow pills, a mixture of many unrelated drugs, such as digitalis, thyroid, and diuretics were found to cause multiple deaths. Then amphetamines [am-FET-ah-meens] were widely available until the late 1970s. Amphetamines are now restricted because they are addicting and may cause side effects on the heart and nervous system. In the 1990s the drugs fenfluramine [fen-FLOO-ra-meen] (previously marketed as Pondimin) and dexfenfluramine [dex-fen-FLOO-ra-meen] (Redux) were used to treat obesity. Fenfluramine was used in combination with phentermine [fen-ter-meen] (Fen-Phen). Fenfluramine and dexfenfluramine were taken off the market after reports of heart valve problems in associati 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 >>
Beyond Diabetes, Metformin May Prove To Be A Wonder Drug
, "Should metformin be the first-line therapy choice in type 2 diabetes treatment?" In the past 2 decades, metformin has become a mainstay of type 2 diabetes management and is now the recommended first-line drug for treating the disease in the United States and worldwide. Available in the United States since 1995, metformin is an attractive therapy for clinicians and patients alike. Studies have found the agent to be safe and effective, and at about $4 for a 1-month supply of the generic, that option is affordable at a time when many prescription drugs are being priced out of reach for some patients. Metformin is the first drug of choice, by all standards, Oluwaranti Akiyode, PharmD, RPh, BCPS, CDE, professor and clinical pharmacist at Howard University School of Pharmacy, told Endocrine Today. Its a rarity that all experts agree on something. It is time-tested, proven, has good efficacy, a good safety profile and its cheap. Metformin has been around long before it came to the United States. Thats why I find it amazing that we only have one drug in that class. New research is suggesting that metformin may hold promise in treating or preventing a whole host of conditions in patients with and without type 2 diabetes. Studies show metformin may be cardioprotective in patients with diabetes and beneficial in the presence of stable congestive heart failure. The agent also may help to increase pregnancy rate in polycystic ovary syndrome, provide breast and prostate cancer benefits, and offer neuroprotection that may reduce dementia and stroke risk, Akiyode said. Nir Barzilai, MD, is exploring whether metformin can target and delay aging, to decrease the incidence of age-related diseases in general, rather than merely decrease the incidence of diabetes. Photo courtesy of Albe Continue reading >>
