Metformin Intolerance Increased By Genes, Other Meds
Metformin Intolerance Increased by Genes, Other Meds STOCKHOLM Genetic variants and certain common medications that interfere with gut absorption of metformin may both be tied to severe intolerance of the drug, new research shows. Metformin is a first-line treatment for type 2 diabetes, used by over 120 million people worldwide. But about 20% of people who take it experience gastrointestinal side effects such as nausea, diarrhea, vomiting, bloating, and abdominal pain. For about 5% of people taking metformin, those symptoms are severe enough to require discontinuation of therapy. "The pathophysiology isn't known but is hypothesized to be related to a high concentration of metformin in the intestine following oral administration," explained Tanja Dujic, PhD, who presented the findings at the recent European Association for the Study of Diabetes (EASD) 2015 Meeting . Dr Dujic was with the faculty of pharmacy at the University of Sarajevo, Bosnia and Herzegovina, at the time the study was conducted but is now a postdoctoral researcher at the University of Dundee, Scotland. In a paper published in May in Diabetes (Diabetes. 2015;64: 1786-1793 ), Dr Dujic and colleagues found associations between severe metformin intolerance and specific genetic variants of a carrier protein involved in the oral absorption, hepatic uptake, and renal elimination of metformin, the organic cation transporter 1 (OCT1). They also found that certain commonly prescribed medications appear to inhibit transport of metformin via OCT1, including tricyclic antidepressants, proton-pump inhibitors (PPIs), and calcium-channel blockers. In her EASD presentation, Dr Dujic summarized the earlier paper and also presented some new data related to the genetic variants. In the earlier study of over 2000 patients Continue reading >>
Metformin
Metformin may rarely cause a serious, life-threatening condition called lactic acidosis. Tell your doctor if you have kidney disease. Your doctor will probably tell you not to take metformin. Also, tell your doctor if you are over 65 years old and if you have ever had a heart attack; stroke; diabetic ketoacidosis (blood sugar that is high enough to cause severe symptoms and requires emergency medical treatment); a coma; or heart or liver disease. Taking certain other medications with metformin may increase the risk of lactic acidosis. Tell your doctor if you are taking acetazolamide (Diamox), dichlorphenamide (Keveyis), methazolamide, topiramate (Topamax, in Qsymia), or zonisamide (Zonegran). Tell your doctor if you have recently had any of the following conditions, or if you develop them during treatment: serious infection; severe diarrhea, vomiting, or fever; or if you drink much less fluid than usual for any reason. You may have to stop taking metformin until you recover. If you are having surgery, including dental surgery, or any major medical procedure, tell the doctor that you are taking metformin. Also, tell your doctor if you plan to have any x-ray procedure in which dye is injected, especially if you drink or have ever drunk large amounts of alcohol or have or have had liver disease or heart failure. You may need to stop taking metformin before the procedure and wait 48 hours to restart treatment. Your doctor will tell you exactly when you should stop taking metformin and when you should start taking it again. If you experience any of the following symptoms, stop taking metformin and call your doctor immediately: extreme tiredness, weakness, or discomfort; nausea; vomiting; stomach pain; decreased appetite; deep and rapid breathing or shortness of breath; dizzi Continue reading >>
Glyburide-metformin, Oral Tablet
Glyburide/metformin oral tablet is available only as a generic drug. It’s not available in a brand-name version. Glyburide/metformin only comes as a tablet you take by mouth. Glyburide/metformin is used to treat type 2 diabetes. This drug has a black box warning. This is the most serious warning from the Food and Drug Administration (FDA). A black box warning alerts doctors and patients about drug effects that may be dangerous. Glyburide/metformin can cause lactic acidosis. Don’t use this drug if you already have lactic acidosis. Lactic acidosis is a rare problem that happens when oxygen levels in your body drop. This leads to a buildup of lactic acid in your bloodstream. The condition can sometimes be fatal. Your risk of lactic acidosis may be higher if you have diabetes with kidney damage or heart failure. Other warnings Surgery or medical procedures warning: If you’re going to have surgery, magnetic resonance imaging (MRI), computerized tomography (CT) scan, or any other procedure, your doctor may temporarily stop your treatment with glyburide/metformin. Having procedures done that use radiocontrast dyes while taking this drug can cause kidney failure or lactic acidosis. Sun sensitivity warning Glyburide/metformin can make your skin more sensitive to the sun. This means you’re more likely to get sunburned. While you’re taking this drug, use sunscreen and wear protective clothing whenever you’re in the sun. Don’t use sun lamps or tanning beds or booths. Low blood sugar (hypoglycemia) warning: Glyburide/metformin can cause severe low blood sugar (hypoglycemia). This can cause seizures or fainting. It’s important to know how to spot and treat low blood sugar reactions as directed by your doctor. Symptoms may include: shakiness nervousness or anxiety swea 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 >>
Metformin Side Effects
For the Consumer Applies to metformin: oral solution, oral tablet, oral tablet extended release Along with its needed effects, metformin may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention. Check with your doctor immediately if any of the following side effects occur while taking metformin: More common Abdominal or stomach discomfort cough or hoarseness decreased appetite diarrhea fast or shallow breathing fever or chills general feeling of discomfort lower back or side pain muscle pain or cramping painful or difficult urination sleepiness Less common Anxiety blurred vision chest discomfort cold sweats coma confusion cool, pale skin depression difficult or labored breathing dizziness fast, irregular, pounding, or racing heartbeat or pulse feeling of warmth headache increased hunger increased sweating nausea nervousness nightmares redness of the face, neck, arms, and occasionally, upper chest seizures shakiness shortness of breath slurred speech tightness in the chest unusual tiredness or weakness Rare Behavior change similar to being drunk difficulty with concentrating drowsiness lack or loss of strength restless sleep unusual sleepiness Some side effects of metformin may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them: More common Acid or sour stomach belching bloated excess air or gas in the stomach or intestines full feeling heartburn indiges Continue reading >>
Type 2 Diabetes Patients With Metformin Intolerance
Type 2 diabetes patients with metformin intolerance This article briefly reviews the strategies used to effectively treat type 2 diabetes patients that are unable to tolerate metformin Department of Pharmacy Practice Ambulatory Care Division, Texas Tech University Health Sciences Center, School of Pharmacy Dallas, Type 2 diabetes mellitus (T2DM) is a global disease that currently affects more than 300 million individuals worldwide and is projected to increase by 55% over the next 20 years.1 By and large most patients diagnosed with T2DM are initially started on metformin as it is considered the optimal first-line therapy by clinical guidelines and consensus recommendations.24 Additionally, it is widely accepted to continue metformin throughout the progression of this chronic disease, even when other therapies are added. With the increasing number of diabetic patients in the world, it can be expected that many patients, for various reasons might be unable to tolerate or have contraindications to metformin use. Major issues of intolerability are usually related to gastrointestinal (GI) side effects or the presence of chronic kidney disease (CKD). This brief review will recommend appropriate treatment options when metformin cannot be used in these two scenarios, taking into account efficacy, adverse effect profiles, comorbid conditions and patient preference. One common cause for metformin intolerability is the GI side effects experienced by many patients. According to the package insert for one brand of metformin commonly available in the US, one study showed that more than 25% of patients experienced nausea and vomiting, and more than 50% of patients experienced diarrhoea. Other less common GI side effects include flatulence, indigestion, and abdominal discomfort.5 Many Continue reading >>
- New metformin may help more patients with type 2 diabetes
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- Is It Time to Change the Type 2 Diabetes Treatment Paradigm? No! Metformin Should Remain the Foundation Therapy for Type 2 Diabetes
Trial Detail - Uk Clinical Trial Gateway
This information is designed to help you decide whether this trial is of interest. In some cases it is provided as a link to more detailed patient information or it may still be awaited from the organisation running the trial. Please look again shortly if the information you need is not here or, if named, contact the researcher named above. Metformin is the first-line treatment for medical management of Type 2 Diabetes. Up to 25% of patients experience significant gastrointestinal symptoms and in approximate 5%, side-effects result in the discontinuation of metformin. It would be of great clinical significance if the underlying cause of this intolerance was identified. Recent data has highlighted a metformin transporter in the gut - Organic Cation Transporter 1(OCT1) - as a potential culprit for the variability in metformin tolerance. Across a diabetic population, up to one in four people were shown to have a single reduced function allele for OCT1, with approximately 8% having two reduced function alleles. This may increase the risk of the individual experiencing metformin-associated side-effects, potentially due to accumulation within the cells lining the intestine. The investigators aim to show that loss of function of OCT1, either due to genetic variation or drug inhibition of OCT1, may lead to an increase in the symptoms associated with metformin intolerance. The study is being undertaken at the Clinical Research Centre in Ninewells Hospital, Dundee. The investigators will recruit participants from the GoDARTS study (Genetics of Diabetes and Audit Research Tayside Study). The participants will be healthy controls, i.e. non-diabetic, and recruited according to their genotype of OCT1 (information from GoDARTS). The volunteers will then enter a matched cross-over stu Continue reading >>
About Metformin
Metformin is a medicine used to treat type 2 diabetes and sometimes polycystic ovary syndrome (PCOS). Type 2 diabetes is an illness where the body doesn't make enough insulin, or the insulin that it makes doesn't work properly. This can cause high blood sugar levels (hyperglycemia). PCOS is a condition that affects how the ovaries work. Metformin lowers your blood sugar levels by improving the way your body handles insulin. It's usually prescribed for diabetes when diet and exercise alone have not been enough to control your blood sugar levels. For women with PCOS, metformin stimulates ovulation even if they don't have diabetes. It does this by lowering insulin and blood sugar levels. Metformin is available on prescription as tablets and as a liquid that you drink. Key facts Metformin works by reducing the amount of sugar your liver releases into your blood. It also makes your body respond better to insulin. Insulin is the hormone that controls the level of sugar in your blood. It's best to take metformin with a meal to reduce the side effects. The most common side effects are feeling sick, vomiting, diarrhoea, stomach ache and going off your food. Metformin does not cause weight gain (unlike some other diabetes medicines). Metformin may also be called by the brand names Bolamyn, Diagemet, Glucient, Glucophage, and Metabet. Who can and can't take metformin Metformin can be taken by adults. It can also be taken by children from 10 years of age on the advice of a doctor. Metformin isn't suitable for some people. Tell your doctor before starting the medicine if you: have had an allergic reaction to metformin or other medicines in the past have uncontrolled diabetes have liver or kidney problems have a severe infection are being treated for heart failure or you have recentl Continue reading >>
Drug Treatment Of Type 2 Diabetes Mellitus In Patients For Whom Metformin Is Contraindicated
Go to: Metformin has long been considered the initial drug therapy choice in the treatment of type 2 diabetes mellitus (T2DM). The most widely recognized clinical guidelines and consensus recommendations endorse its use when monotherapy is initially preferred to treat hyperglycemia.1–4 However, treatment with metformin is not suitable for all patients diagnosed with T2DM. Patients may initially receive metformin but not be able to tolerate common side effects, mainly its gastrointestinal adverse effects. Likewise, some practitioners may be cautious in using metformin in patients at risk for but who do not necessarily currently have specific contraindications to its use. While the specific contraindications to use of metformin have changed to an extent over the last decade, significant renal impairment or conditions that could acutely alter renal function remain a consistent theme in delineating who should not receive the medication. Some of the common sources and specific contraindications to the use of metformin based on renal function are provided in Table 1. Inconsistencies between these sources remain. Current guidelines/consensus recommendations for specific therapies to initiate in patients who cannot tolerate or have a contraindication to metformin use provide some insight on the issue but also conflict with each other. The American Diabetes Association/European Association for the Study of Diabetes recommend a sulfonylurea, meglitinide, pioglitazone, or dipeptidyl peptidase 4 (DPP-4) inhibitor when metformin cannot be used.3 They also recommend using a glucagon-like peptide-1 (GLP-1) agonist if weight loss is warranted. The American Association of Clinical Endocrinologists state GLP-1 agonists, DPP-4 inhibitors, and alpha-glucosidase inhibitors are acceptable Continue reading >>
Metformin - Oral, Glucophage
are allergic to dapagliflozin or any of the ingredients in FARXIGA. Symptoms of a serious allergic reaction may include skin rash, raised red patches on your skin (hives), swelling of the face, lips, tongue, and throat that may cause difficulty in breathing or swallowing. If you have any of these symptoms, stop taking FARXIGA and contact your healthcare provider or go to the nearest hospital emergency room right away have severe kidney problems or are on dialysis. Your healthcare provider should do blood tests to check how well your kidneys are working before and during your treatment with FARXIGA Dehydration (the loss of body water and salt), which may cause you to feel dizzy, faint, lightheaded, or weak, especially when you stand up (orthostatic hypotension). You may be at a higher risk of dehydration if you have low blood pressure; take medicines to lower your blood pressure, including water pills (diuretics); are 65 years of age or older; are on a low salt diet, or have kidney problems Ketoacidosis occurred in people with type 1 and type 2 diabetes during treatment with FARXIGA. Ketoacidosis is a serious condition which may require hospitalization and may lead to death. Symptoms may include nausea, tiredness, vomiting, trouble breathing, and abdominal pain. If you get any of these symptoms, stop taking FARXIGA and call your healthcare provider right away. If possible, check for ketones in your urine or blood, even if your blood sugar is less than 250 mg/dL Kidney problems. Sudden kidney injury occurred in people taking FARXIGA. Talk to your doctor right away if you reduce the amount you eat or drink, or if you lose liquids; for example, from vomiting, diarrhea, or excessive heat exposure Serious urinary tract infections (UTI), some that lead to hospitalization, occu Continue reading >>
Personalized Medicine For Metformin Therapy?
Personalized Medicine for Metformin Therapy? This article is intended for primary care clinicians, endocrinologists, geneticists, nurses, pharmacists, and other clinicians who care for patients who might use metformin. The goal of this activity is to provide medical news to primary care clinicians and other healthcare professionals in order to enhance patient care. Upon completion of this activity, participants will be able to: Evaluate the epidemiology and symptoms of metformin intolerance Distinguish factors associated with intolerance to metformin in the current study As an organization accredited by the ACCME, Medscape, LLC, requires everyone who is in a position to control the content of an education activity to disclose all relevant financial relationships with any commercial interest. The ACCME defines "relevant financial relationships" as financial relationships in any amount, occurring within the past 12 months, including financial relationships of a spouse or life partner, that could create a conflict of interest. Medscape, LLC, encourages Authors to identify investigational products or off-label uses of products regulated by the US Food and Drug Administration, at first mention and where appropriate in the content. Disclosure: Miriam E. Tucker has disclosed no relevant financial relationships. Disclosure: Robert Morris, PharmD, has disclosed no relevant financial relationships. Disclosure: Charles P. Vega, MD, has disclosed the following financial relationships: Served as an advisor or consultant for: Lundbeck, Inc.; McNeil Pharmaceuticals; Takeda Pharmaceuticals North America, Inc. Disclosure: Amy Bernard, MS, BSN, RN-BC, has disclosed no relevant financial relationships. Medscape, LLC is accredited by the Accreditation Council for Continuing Medical Educat Continue reading >>
Metformin And The Gastrointestinal Tract
Go to: Introduction Metformin—dimethylbiguanide—is an oral glucose-lowering agent. Its origins can be traced to Galega officinalis, also known as French lilac or goat’s rue [1]. In the early 20th century it was noted to lower blood glucose concentrations in animals, but it was not until the 1950s that Jean Sterne studied dimethylbiguanide and subsequently developed ‘Glucophage’ [2]. Over the last 15 years, metformin has become the first-line agent for the treatment of type 2 diabetes, as noted in several international guidelines, including the ADA-EASD guidelines [3]. Metformin has had a chequered history—it was initially eclipsed by phenformin, which was withdrawn in the late 1970s after it was discovered to be associated with lactic acidosis [4]. The lower propensity of metformin for hyperlactataemia [5] and success in several large randomised controlled clinical trials, such as the UK Prospective Diabetes Study (UKPDS) [6], confirmed its clinical benefit. It is widely recognised that metformin improves glycaemic control with a good safety profile, weight neutrality or weight loss, lack of associated hypoglycaemia, reduced cardiovascular mortality and low cost [3]. However, a large proportion of patients cannot tolerate the medication in adequate amounts because of its associated side effects. Up to 25% of patients suffer metformin-associated gastrointestinal (GI) side-effects, with approximately 5% unable to tolerate metformin at all [7]. In addition to this interindividual variation in side effects, there is variability in the efficacy of metformin. There are likely to be a number of factors to account for this variability in efficacy, for example, our group (Zhou et al) recently established that the glycaemic response to metformin is moderately heritabl Continue reading >>
Pharmacokinetics Of Metformin In Patients With Gastrointestinal Intolerance
Pharmacokinetics of metformin in patients with gastrointestinal intolerance Research output: Research - peer-review Journal article AIMS: Metformin intolerance symptoms are gastrointestinal in nature, but the underlying mechanism is poorly understood. The aim of this study was to assess potential causes of metformin intolerance including: altered metformin uptake from the intestine; increased anaerobic glucose utilisation and subsequent lactate production; altered serotonin uptake; and altered bile acid pool. METHODS: This pharmacokinetic study recruited ten severely intolerant and ten tolerant individuals matched for age, sex and BMI. A single 500mg dose of metformin was administered, with blood sampling at eleven time points over 24 hours. Blood samples were analysed for metformin, lactate, serotonin, and bile acid concentrations and compared across the phenotypes. RESULTS: The intolerant individuals were severely intolerant to 500mg metformin. No significant difference was identified between tolerant and intolerant cohorts in metformin pharmacokinetics: median Cmax2.1 (IQR 1.7 - 2.3) and 2.0 (IQR 1.8 - 2.2) mg/L respectively (p = 0.76); tmax2.5 hours; median AUC0-2416.9 (IQR 13.9 - 18.6) and 13.9 (IQR 12.9 - 16.8) (mg/L)*h respectively (p = 0.72). Lactate concentration peaked at 3.5 hours, with mean peak concentration of 2.4 mmol/L in both cohorts (95% CIs 2.0 - 2.8, and 1.8 - 3.0 mmol/L respectively), and comparable iAUC0-24: tolerant 6.98 (3.03 -10.93) and intolerant 4.47 (-3.12 - 12.06) mmol/L*h, (p=0.55). Neither serotonin nor bile acid concentrations were significantly different. CONCLUSIONS: Despite evidence of severe intolerance in our cohort, there was no significant difference in metformin pharmacokinetics or systemic measures of lactate, serotonin or bile Continue reading >>
Metformin Hcl Side Effects By Likelihood And Severity
are allergic to dapagliflozin or any of the ingredients in FARXIGA. Symptoms of a serious allergic reaction may include skin rash, raised red patches on your skin (hives), swelling of the face, lips, tongue, and throat that may cause difficulty in breathing or swallowing. If you have any of these symptoms, stop taking FARXIGA and contact your healthcare provider or go to the nearest hospital emergency room right away have severe kidney problems or are on dialysis. Your healthcare provider should do blood tests to check how well your kidneys are working before and during your treatment with FARXIGA Dehydration (the loss of body water and salt), which may cause you to feel dizzy, faint, lightheaded, or weak, especially when you stand up (orthostatic hypotension). You may be at a higher risk of dehydration if you have low blood pressure; take medicines to lower your blood pressure, including water pills (diuretics); are 65 years of age or older; are on a low salt diet, or have kidney problems Ketoacidosis occurred in people with type 1 and type 2 diabetes during treatment with FARXIGA. Ketoacidosis is a serious condition which may require hospitalization and may lead to death. Symptoms may include nausea, tiredness, vomiting, trouble breathing, and abdominal pain. If you get any of these symptoms, stop taking FARXIGA and call your healthcare provider right away. If possible, check for ketones in your urine or blood, even if your blood sugar is less than 250 mg/dL Kidney problems. Sudden kidney injury occurred in people taking FARXIGA. Talk to your doctor right away if you reduce the amount you eat or drink, or if you lose liquids; for example, from vomiting, diarrhea, or excessive heat exposure Serious urinary tract infections (UTI), some that lead to hospitalization, occu Continue reading >>
Is It Safe To Mix Metformin And Alcohol?
If you’re taking metformin to treat your diabetes, you may be wondering how this drug affects your ability to drink safely. Drinking alcohol can affect your diabetes symptoms directly, but there are additional risks if you drink alcohol with metformin. This article gives you information on how alcohol interacts with metformin and also how drinking alcohol can affect your diabetes. With any medicine you take, you should be aware of interactions that can happen if you use other substances. Metformin and alcohol can interact to increase your risk of harmful effects. You are at much greater risk of these effects if you frequently drink a lot of alcohol or you binge drink (drink a lot in short periods). These effects include an extremely low blood sugar level, called hypoglycemia, and a condition called lactic acidosis. Hypoglycemia Drinking alcohol while you’re taking metformin may cause extremely low blood sugar levels. Some symptoms of low blood sugar levels can be similar to symptoms of having too much alcohol. These include: drowsiness dizziness confusion Tell the people who are with you while you drink that you have diabetes. They can help you watch for these symptoms. If you or the people around you notice these symptoms, stop drinking and eat something right away to help increase your blood sugar level. If your symptoms of hypoglycemia are severe, such as losing consciousness, and you do not have a glucagon hypoglycemia rescue kit, someone with you should call 9-1-1. A glucagon hypoglycemia rescue kit includes human glucagon (a natural substance that helps balance your blood sugar level), a syringe to inject it, and instructions. You can use this kit for severe hypoglycemia when eating food will not help. If you are not familiar with this kit, talk to your doctor Continue reading >>
