All concepts, explanations, trials, and studies have been re-written in plain English and may contain errors. I am not a doctor ----------------------------------------------------------- Glucophage/metformin - a diabetes drug - is in the news. Here is a series of articles and info bytes to bring you up to date: Metformin HCL (glucophage) should not be taken by patients with: 1. weak kidney function or kidney disease - blood creatinine levels over 1.4 mg/dl. 2. congestive heart failure requiring drug treatment. 3. known sensitivity to metformin HCL. 4. Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma. 5. Metformin HCL should be stopped in patients having radiology studies using injected dye of any kind. Glucophage warnings: (Lactic Acidosis is the buildup of lactic acid in the blood) Lactic acidosis is a rare but serious complication that can occur due to glucophage accumulation. It is fatal 50% of the time. Lactic acidosis causes high blood lactate levels (over 5 mmol/L), lowered blood pH and electrolyte disturbances. Heart failure patients taking heart failure meds are at risk of lactic acidosis when taking this drug. Risk increases with age. People over 80 years of age should not take the drug. Patients with weak liver function or liver disease should not take this drug. Patients should not drink excessive alcohol when taking metformin HCL. The drug should be stopped before any imaging test requiring use of any kind of injected dye, and before any surgery. Onset of lactic acidosis may be subtle, with only vague symptoms such as malaise, muscle weakness or pain, difficulty breathing, tendency to be sleepy and tired, and abdominal distress. There may also be low body temperature, low blood pressure, and slow heart rate. Notify your doctor immediately if these symptoms occur while taking glucophage - the drug should be stopped until the situation is clarified. Lactic acidosis is a medical emergency that must be treated in a hospital! In a patient with lactic acidosis who is taking metformin HCL, the drug should be stopped immediately. Prompt dialysis may correct the acidosis and remove the accumulated metformin. ------------------------------------------------------------ Special warning: Increased risk of heart-related death Oral diabetes drugs may increase heart-related mortality compared to treatment with diet alone or diet plus insulin. This warning is based on a study done by the University Group Diabetes Program, a long-term trial studying the effectiveness of glucose-lowering drugs for preventing or delaying vascular complications in patients with non-insulin-dependent diabetes. The study involved 1,027 patients randomly assigned to one of 5 treatment groups - See the journal Diabetes, 19 (Suppl.2):747-830, 1970 and Diabetes, 24 (Suppl.1):65-184, 1975). Patients treated for 5 to 8 years with diet plus 1.5 gram per day of tolbutamide; or diet plus 100mg per day phenformin, had a rate of cardiovascular mortality 2.5 times higher than patients treated with diet alone. ---------------------------------------------------------- Radiology studies (imaging) using injected dye can acutely reduce kidney function, and have been linked to lactic acidosis in patients taking metformin HCL. Glucophage should be stopped before such a procedure, and withheld for 48 hours afterward or until kidney function tests normal. ---------------------------------------------------------- Metformin HCL should be stopped before any surgical procedure that requires restricting food and fluid intake. It should not be restarted until the patient is eating again and his kidney function tests normal. ---------------------------------------------------------- From Bristol-Myers Squibb's web site (the drug's manufacturer): See http://www.glucophagexr.com/ Glucophage is not for everyone. In rare cases, it may cause lactic acidosis, which is fatal in half the cases. This occurs mainly in people whose kidneys are not functioning properly. Tell your doctor about your alcohol use because it can affect your risk. You should not take this drug if you: 1) have kidney problems 2) are 80 or older 3) are taking drugs for heart failure 4) are seriously dehydrated 5) have a severe infection 6) have or have had liver disease. ---------------------------------------------------------- From Reuters Health By Maggie Fox, Health and Science Correspondent May 15, 2002 - Doctors are wrongly prescribing a diabetes drug to patients with heart failure or kidney failure, putting them at risk of deadly complications. Metformin, sold under the name Glucophage and also available as a generic, is the most widely used drug for treating type II (adult-onset) diabetes. It should not be used by patients who are taking drugs for kidney failure OR HEART FAILURE but researchers at the University of North Carolina found that 22 of 100 patients they picked at random who were taking metformin had one or both of the conditions. "We are concerned that these patients may be at risk of a serious medical condition known as lactic acidosis, which can be kill you," Dr. Cheryl Horlen said (study author). Lactic acidosis is a rare metabolic condition and it kills half the patients who develop it. It is so dangerous that metformin tablets carry what is called an FDA 'black box' warning - a bold and easy to see block of text in the package insert. However, doctors are not paying attention, Horlen said. The FDA said it received reports of 47 confirmed cases of lactic acidosis linked to glucophage use in the first 14 months after its release in the USA ; and 42% of these patients died. Horlen searched medical records for the study. "We found 241 patients who had 2 or more prescriptions for metformin in a 9 month period. We randomly selected 100 of these for a chart review," she said. They found 14 of the patients had heart failure, 5 had kidney dysfunction and 3 had both. This is not the first time a diabetes drug has been widely prescribed despite well-known dangers. Pfizer withdrew its highly successful drug Rezulin in March of 2000 after more than 100 patients were hospitalized with liver failure and 26 died of it - this despite the fact that the FDA had repeatedly warned doctors to monitor liver function of patients taking Rezulin. Another group of researchers from the University of Pittsburgh recently reported that more than 25% of diabetics taking metformin at the hospital had a condition that placed them at higher risk for complications. ------------------------------------------------------------- Title: Frequency of Inappropriate Metformin Prescriptions From: The Journal of the American Medical Association 2002;287:2504-2505; Research Letters Section To the Editor: Metformin is commonly used to manage type 2 diabetes. More than 25 million prescriptions for metformin were written in 2000, making it the most commonly prescribed diabetes drug in the USA. Metformin is linked to lactic acidosis. Since its approval in 1995, the FDA has required a 'black box' warning in the package insert. The drug is labeled NOT to be used in patients with kidney dysfunction OR CONGESTIVE HEART FAILURE requiring drug treatment. We studied how often glucophage was used in a sample group of patients with these 2 primary contraindications. We reviewed charts of patients taking metformin at a university medical center. All patients with 2 or more prescriptions for metformin between January 1 of 2000 and September 30 of 2000 were identified. These patient records were randomized using a random number generator. Kidney dysfunction was defined as a blood creatinine level higher than 1.5 mg/dL (132.6 micro-mol/L) for men and higher than 1.4 mg/dL (123.8 micro-mol/L) for women. Patient records were also reviewed to see if the potential for problems with the drug had been considered before prescribing it. Pharmacy records identified 241 patients with 2 or more prescriptions for metformin; 100 were randomly selected for chart review. Twenty-two patients (22%) had either heart failure requiring drug treatment or weak kidney function. Of these 22 patients, 14 had heart failure only, 5 had weak kidneys only, and 3 had both. Only 2 of all these patients had documentation in their medical record that their doctor had considered the drug's dangers in their case. CONCLUSIONS In our review, almost 25% of patients with a prescription for glucophage had one or more absolute contraindications to using the drug. Several recent studies in Europe have shown similar rates of wrong and dangerous glucophage prescribing. In the first 14 months after its release in the USA, the FDA saw 47 confirmed cases of lactic acidosis linked to metformin, with a 42% mortality rate. More than 90% of these patients had contraindications to the drug and should not have been given it. Our study may actually underestimate the number of patients getting glucophage who are at risk for death from using the drug. Our results suggest that metformin is often prescribed to at-risk patients despite the black-box warning. Cheryl Horlen, PharmD - School of Pharmacy, Campbell University, Buies Creek, North Carolina Robb Malone, PharmD, CDE and Betsy Bryant, PharmD, CDE - Department of Medicine, University of North Carolina at Chapel Hill Betty Dennis, PharmD, MS, CDE - University of North Carolina Hospital Pharmacy at Chapel Hill Tim Carey, MD, MPH and Mike Pignone, MD, MPH and Russell Rothman, MD, MPP - Department of Medicine, University of North Carolina at Chapel Hill