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Why Is Metformin Contraindicated In Ketoacidosis

Important Safety Information For Invokana®, Invokamet® (canagliflozin/metformin Hcl), And Invokamet® Xr (canagliflozin/metformin Hcl Extended-release)

Important Safety Information For Invokana®, Invokamet® (canagliflozin/metformin Hcl), And Invokamet® Xr (canagliflozin/metformin Hcl Extended-release)

WARNING: LACTIC ACIDOSIS AND LOWER-LIMB AMPUTATION Lactic Acidosis Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. The onset of metformin-associated lactic acidosis is often subtle, accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, somnolence, and abdominal pain. Metformin-associated lactic acidosis was characterized by elevated blood lactate levels (>5 mmol/L); anion gap acidosis (without evidence of ketonuria or ketonemia); an increased lactate:pyruvate ratio; and metformin plasma levels generally >5 mcg/mL. Risk factors for metformin-associated lactic acidosis include renal impairment, concomitant use of certain drugs (eg, carbonic anhydrase inhibitors such as topiramate), age 65 years old or greater, having a radiological study with contrast, surgery and other procedures, hypoxic states (eg, acute congestive heart failure), excessive alcohol intake, and hepatic impairment. Steps to reduce the risk of and manage metformin-associated lactic acidosis in these high-risk groups are provided in the full prescribing information. If metformin-associated lactic acidosis is suspected, immediately discontinue INVOKAMET®/ INVOKAMET® XR and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended. Risk of Lower-Limb Amputation An approximately 2-fold increased risk of lower-limb amputations associated with canagliflozin, a component of INVOKAMET®/INVOKAMET® XR, was observed in CANVAS and CANVAS-R, two large, randomized, placebo-controlled trials in patients with type 2 diabetes who had established cardiovascular disease (CVD) or were at risk for CVD. Amputations of the toe and midfoot were most frequent; Continue reading >>

Ketoacidosis: A Diabetes Complication

Ketoacidosis: A Diabetes Complication

Ketoacidosis can affect both type 1 diabetes and type 2 diabetes patients. It's a possible short-term complication of diabetes, one caused by hyperglycemia—and one that can be avoided. Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) are two of the most serious complications of diabetes. These hyperglycemic emergencies continue to be important causes of mortality among persons with diabetes in spite of all of the advances in understanding diabetes. The annual incidence rate of DKA estimated from population-based studies ranges from 4.8 to 8 episodes per 1,000 patients with diabetes. Unfortunately, in the US, incidents of hospitalization due to DKA have increased. Currently, 4% to 9% of all hospital discharge summaries among patients with diabetes include DKA. The incidence of HHS is more difficult to determine because of lack of population studies but it is still high at around 15%. The prognosis of both conditions is substantially worsened at the extremes of age, and in the presence of coma and hypertension. Why and How Does Ketoacidosis Occur? The pathogenesis of DKA is more understood than HHS but both relate to the basic underlying reduction in the net effective action of circulating insulin coupled with a concomitant elevation of counter regulatory hormones such as glucagons, catecholamines, cortisol, and growth hormone. These hormonal alterations in both DKA and HHS lead to increased hepatic and renal glucose production and impaired use of glucose in peripheral tissues, which results in hyperglycemia and parallel changes in osmolality in extracellular space. This same combination also leads to release of free fatty acids into the circulation from adipose tissue and to unrestrained hepatic fatty acid oxidation to ketone bodies. Some drugs ca Continue reading >>

Lactic Acidosis In A Patient With Type 2 Diabetes Mellitus

Lactic Acidosis In A Patient With Type 2 Diabetes Mellitus

Introduction A 49-year-old man presented to the emergency department complaining of dyspnea for 2 days. He had a history of hypertension, type 2 diabetes mellitus, atrial fibrillation, and a severe dilated cardiomyopathy. He had been hospitalized several times in the previous year for decompensated congestive heart failure (most recently, 1 month earlier). The plasma creatinine concentration was 1.13 mg/dl on discharge. Outpatient medications included insulin, digoxin, warfarin, spironolactone, metoprolol succinate, furosemide (80 mg two times per day; increased from 40 mg daily 1 month earlier), metolazone (2.5 mg daily; added 1 month earlier), and metformin (2500 mg in three divided doses; increased from 1000 mg 1 month earlier). Physical examination revealed an obese man in moderate respiratory distress. The temperature was 36.8°C, BP was 119/83 mmHg, and heart rate was 96 per minute. Peripheral hemoglobin oxygen saturation was 97% on room air, with a respiratory rate of 26 per minute. The heart rhythm was irregularly irregular; there was no S3 or murmur. Jugular venous pressure was about 8 cm. There was 1+ edema at the ankles. A chest radiograph showed cardiomegaly and central venous prominence. The N-terminal pro-B-type natriuretic peptide level was 5137 pg/ml (reference range = 1–138 pg/ml). The peripheral hemoglobin concentration was 12.5 g/dl, the white blood cell count was 12,500/µl (76% granulocytes), and the platelet count was 332,000/µL. Initial plasma chemistries are shown in Table 1. The impression was decompensated congestive heart failure. After administration of furosemide (160 mg intravenously), the urine output increased to 320 ml over the next 1 hour. There was no improvement in the dyspnea. Within 2 hours, the patient’s BP fell to 100/64 mmHg Continue reading >>

Metformin / Repaglinide Disease Interactions

Metformin / Repaglinide Disease Interactions

Major Meglitinides (Includes Metformin/repaglinide) ↔ Type I Diabetes Severe Potential Hazard, Moderate plausibility Applies to: Diabetes Type 1, Diabetic Ketoacidosis The use of meglitinides is contraindicated in patients with type I diabetes or for the treatment of diabetic ketoacidosis, with or without coma. Major Metformin (Includes Metformin/repaglinide) ↔ Lactic Acidosis Severe Potential Hazard, High plausibility Applies to: Renal Dysfunction, Liver Disease, Congestive Heart Failure, Dehydration, Shock, Myocardial Infarction, Asphyxia, Acidosis, Diarrhea, Vomiting, Anemia, Alcoholism The use of metformin is contraindicated in patients with renal dysfunction (serum creatinine >= 1.5 mg/dL in males and 1.4 mg/dL in females, or above the upper limit of normal for age); congestive heart failure requiring pharmacologic treatment (especially unstable or acute CHF where there is risk of hypoperfusion and hypoxemia); and any condition associated with hypoxemia (e.g., severe anemia, myocardial infarction, asphyxia, shock), dehydration (e.g., severe diarrhea or vomiting), or sepsis. Patients with these conditions may be at increased risk for the development of lactic acidosis, which is a rare but serious metabolic complication associated with metformin accumulation in plasma usually at levels exceeding 5 mcg/mL. Metformin should also not be administered to patients with acute or chronic metabolic acidosis. In addition, metformin should generally be avoided in alcoholics and patients with clinical or laboratory evidence of hepatic disease, since alcohol potentiates the effects of metformin on lactate metabolism and impaired hepatic function may significantly limit the ability to clear lactate. All patients treated with metformin should have renal function monitored regul Continue reading >>

Guidelines For Perioperative Management Of The Diabetic Patient

Guidelines For Perioperative Management Of The Diabetic Patient

Surgery Research and Practice Volume 2015 (2015), Article ID 284063, 8 pages 1Texas A&M Health Science Center, 8447 State Highway 47, Bryan, TX 77807, USA 2Division of Pulmonary, Critical Care & Sleep Medicine, Texas A&M Health Science Center, Corpus Christi, 1177 West Wheeler Avenue, Suite 1, Aransas Pass, TX 78336, USA Academic Editor: Roland S. Croner Copyright © 2015 Sivakumar Sudhakaran and Salim R. Surani. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Management of glycemic levels in the perioperative setting is critical, especially in diabetic patients. The effects of surgical stress and anesthesia have unique effects on blood glucose levels, which should be taken into consideration to maintain optimum glycemic control. Each stage of surgery presents unique challenges in keeping glucose levels within target range. Additionally, there are special operative conditions that require distinctive glucose management protocols. Interestingly, the literature still does not report a consensus perioperative glucose management strategy for diabetic patients. We hope to outline the most important factors required in formulating a perioperative diabetic regimen, while still allowing for specific adjustments using prudent clinical judgment. Overall, through careful glycemic management in perioperative patients, we may reduce morbidity and mortality and improve surgical outcomes. 1. Introduction Diabetes has classically been defined as a group of metabolic diseases characterized by hyperglycemia due to defects in insulin secretion, insulin action, or a combination of both [1]. The vast majority of di Continue reading >>

What Medications Can Be Used As A Substitute For Metformin

What Medications Can Be Used As A Substitute For Metformin

Metformin is a prescription medication used for treatment of type 2 (non-insulin dependent) diabetes. Other medications may be considered if metformin does not adequately treat your type 2 diabetes. Types Types of medications for treating type 2 diabetes include dipeptidyl-peptidase 4 inhibitors such as Onglyza and Januvia, glucagon-like peptide 1 agonists such as Byetta, meglitinides such as Prandin and Starlix, sulfonylureas such as Glucotrol, Amaryl and Glynase, thiazolidinediones such as Avandia and Actos and alpha-glucosidase inhibitors such as Precose and Glyset. Function DPP-4 inhibitors, GLP-1 agonists, meglitinides and sulfonylureas increase insulin production, thiazolidinediones increases the effectiveness of insulin without increasing insulin production and alpha-glucosidase inhibitors blocks certain stomach enzymes that make the body more sensitive to insulin. Administration Byetta is available only as an injectable. The other types of medications are taken orally. Side Effects Sulfonylureas and thiazolidediones may cause weight gain. DPP-4 inhibitors increase risk of respiratory infections. Consult your pharmacist or physician for a more comprehensive list of side effects for each particular medication. Lactic Acidosis Metformin may cause lactic acidosis, which is a condition caused by excessive buildup of lactic acid in the body. Symptoms of lactic acidosis include weakness, drowsiness, decreased heart rate, cold feeling, muscle pain, shortness of breath, stomach pain, lightheadedness and fainting. Other types of type 2 diabetes medications are not associated with development of lactic acidosis. Diabetic Ketoacidosis Metformin is contraindicated in cases of diabetic ketoacidosis, a condition caused by a shortage of insulin in the body. DDP-4 inhibitors, GL Continue reading >>

Diabetic Ketoacidosis

Diabetic Ketoacidosis

Diabetic ketoacidosis (DKA) is a life-threatening condition when the body has practically no insulin. This insulin deficiency results in extremely high blood sugar levels. Consequently, the muscle, fat and liver cells cannot use glucose for fuel. These cells are converted into glucose by hormones such as glucagon and adrenalin and turned into ketones through oxidation. As a result, the body uses fat for fuel. The increased levels of blood sugar are not flushed through urination. DKA is usually noticed in patients suffering from Insulin-dependent diabetes. A person can suffer from diabetic ketoacidosis if there has been severe dehydration and consequently the blood chemistry has been affected. There is accumulation of organic acids and ketones in the blood. Elevated ketone levels in the body upset its blood pH and make the blood acidic thereby triggering a toxic condition for the body's cells. Diabetic ketoacidosis is noticed when hyperglycemia exceeds 300 mg/dL. If diabetes ketoacidosis is not addressed in time, it can lead to coma and death. Surgery, infection, trauma, stroke or heart attack can also trigger diabetes ketoacidosis. Insufficient fluid intake, pancreatitis and alcohol abuse can trigger diabetes ketoacidosis. Symptoms of diabetes ketoacidosis include excessive thirst and general weakness. There is frequent urination, loss of appetite and vomiting. Other symptoms of diabetes ketoacidosis are weight loss and abdominal pain. A person suffering from DKA tends to experience low blood pressure and increased heart rate. High ketone levels can give rise to a fruity-scent on the breath and vomiting. The patient will be restless and agitated. The skin will be hot and dry and appear flushed. Patients suffering from diabetes must check their blood glucose levels if th Continue reading >>

Metformin

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 >>

To Initiate Synjardy Or Synjardy Xr, Determine Appropriate Combination Of The Active Ingredient Of Jardiance And Metformin*

To Initiate Synjardy Or Synjardy Xr, Determine Appropriate Combination Of The Active Ingredient Of Jardiance And Metformin*

Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. Symptoms included malaise, myalgias, respiratory distress, somnolence, and abdominal pain. Laboratory abnormalities included elevated blood lactate levels, anion gap acidosis, increased lactate/pyruvate ratio, and metformin plasma levels generally >5 mcg/mL. Risk factors include renal impairment, concomitant use of certain drugs, age ≥65 years old, radiological studies with contrast, surgery and other procedures, hypoxic states, excessive alcohol intake, and hepatic impairment. Steps to reduce the risk of and manage metformin-associated lactic acidosis in these high risk groups are provided in the Full Prescribing Information. If lactic acidosis is suspected, discontinue SYNJARDY or SYNJARDY XR and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended. JARDIANCE is indicated to reduce the risk of cardiovascular (CV) death in adults with type 2 diabetes mellitus and established CV disease. JARDIANCE, SYNJARDY, AND SYNJARDY XR are indicated as adjuncts to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. SYNJARDY and SYNJARDY XR are indicated when both empagliflozin and metformin hydrochloride are appropriate. Empagliflozin, a component of SYNJARDY AND SYNJARDY XR, is indicated to reduce the risk of CV death in adults with type 2 diabetes mellitus and established CV disease. However, the effectiveness of SYNJARDY AND SYNJARDY XR on reducing the risk of CV death in adults with type 2 diabetes mellitus and CV disease has not been established. JARDIANCE, SYNJARDY, AND SYNJARDY XR are not recommended for patients with type 1 diabetes or for the treatment of Continue reading >>

Sglt2 Inhibitors

Sglt2 Inhibitors

SGLT2 inhibitors are not indicated for treatment of adults with type 1 diabetes mellitus, a metabolic disorder that also is characterized by hyperglycemia. In type 1 diabetics, however, the pancreas produces little to no insulin. Sodium glucose cotransporter-2 (SGLT2) inhibitors are a novel class of antihyperglycemics designed to work against SGLT2, a low-affinity, high-capacity transporter protein found in the kidney’s proximal tubules. The mechanism for SGLT2 inhibitors involves preventing the excretion of urinary glucose by reabsorbing glucose. SGLT2 inhibitors discourage this reuptake of glucose in the kidney. SGLT2 inhibitors are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus, a metabolic disorder commonly characterized by hyperglycemia (high blood sugar) and inadequate levels of insulin or insulin resistance. Some SGLT2 inhibitors have been linked to side effects ranging from UTIs to kidney problems, amputations, bladder cancer and diabetic ketoacidosis (dka). Using SGLT2 inhibitors for the Treatment of Type 2 Diabetes Generally, SGLT2 inhibitors are taken orally once per day, usually before breakfast. Your doctor will prescribe the strength of the pill and tell you exactly how and when to take it. The dose may be changed if your doctor decides doing so would be more beneficial for you. While taking an SGLT2 inhibitor, your doctor may advise you to check your blood sugar levels in accordance with a particular schedule. Be aware that SGLT2 inhibitors will be likely to cause your urine to test positive for glucose. Your doctor may also order tests to check your blood sugar levels and hemoglobin A1C while taking SGLT2 inhibitors. Your doctor may periodically order these same tests, and possibly other Continue reading >>

Oral Hypoglycemic Agents

Oral Hypoglycemic Agents

Oral Antihyperglycemic Drugs Oral antihyperglycemic agents lower glucose levels in the blood. They are commonly used in the treatment of diabetes mellitus. [1] Biguanides Sulfonylureas Thiazolidinediones Alpha-glucosidase inhibitors Inhibit the upper gastrointestinal enzymes that convert dietary starch and other complex carbohydrates into simple sugars, which can be absorbed Contraindications: Diabetic ketoacidosis; cirrhosis; inflammatory bowel disease, colonic ulceration, partial intestinal obstruction, Continue reading >>

Diabetes Management In Cancer Patients

Diabetes Management In Cancer Patients

Hyperglycemia is a common challenge during cancer treatment and palliation. In addition, many patients with pre-existing type 1 or type 2 diabetes undergoing cancer treatment develop iatrogenic hyperglycemia with unique features. The most common example is steroid-induced hyperglycemia,[1] but several other scenarios are common and clinically important (Table 1). Special considerations are often necessary regarding standard lifestyle recommendations, optimal choice of antidiabetic drug (Table 2), and goals of therapy.[2] In patients with active cancer, the focus of hyperglycemia management shifts from preventing long-term complications toward avoiding acute and subacute outcomes, such as dehydration from polyuria, infection, catabolic weight loss, hyperosmolar nonketotic states (HNK), and diabetic ketoacidosis (DKA; Table 3).[3,4] It should be noted that the truly emergent conditions HNK and DKA are rare. The more common scenario of an asymptomatic severe elevation in blood glucose level (> 400 mg/dL, for example), although requiring a treatment plan with good hydration and close follow-up, does not typically require an emergency room visit or admission. Two representative clinical cases are presented here. Clinical Vignette #1 Corticosteroid-induced hyperglycemia A 53-year-old woman with a history of pre-diabetes and peripheral blood stem cell transplant for acute myelogenous leukemia (AML) presented with asymptomatic elevated random blood glucose levels. After transplant she developed graft-versus-host disease (GVHD) with liver injury, which was treated with 60 mg of prednisone daily, tapered gradually to 20 mg daily at the time of presentation 2 months later. Random serum glucose level was 396 mg/dL. Previously, all serum glucose levels had been less than 160 mg/dL u Continue reading >>

Three Diabetes Drugs Linked To Ketoacidosis, Fda Warns

Three Diabetes Drugs Linked To Ketoacidosis, Fda Warns

NASHVILLE -- Three type 2 diabetes drugs -- canagliflozin (Invokana), dapagliflozin (Farxiga), and empagliflozin (Jardiance) -- may lead to ketoacidosis, the FDA warned today. The sodium-glucose co-transporter-2 (SGLT2) inhibitors are designed to lower blood sugar in patients with diabetes, but the FDA is investigating a connection between the drugs and dangerously high acid levels in the blood. They are also looking at whether changes will need to be made to the prescribing information, they said in the warning, which is posted online. At least two studies presented here at the annual meeting of the American Association of Clinical Endocrinologists have found a connection between the SGLT2 inhibitors and diabetic ketoacidosis (DKA). "Healthcare professionals should evaluate for the presence of acidosis, including ketoacidosis, in patients experiencing these signs or symptoms," the FDA said. "Discontinue SGLT2 inhibitors if acidosis is confirmed, and take appropriate measures to correct the acidosis and monitor sugar levels." The signs and symptoms listed included difficulty breathing, nausea, vomiting, abdominal pain, confusion, and unusual fatigue or sleepiness. The FDA is issuing the warning after they searched their database of adverse event complaints, they said in an announcement. From March 2013 to June 2014 there were 20 cases of DKA reported, most of them with type 2 diabetes as the indication. Hospitalization was required in all of the cases, and the median time to onset was 2 weeks after starting the drug. "I would encourage that these cases be studied so we can learn the scenarios behind them so they can be broadcast," said Farhad Zangeneh, MD, medical director of Endocrine, Diabetes and Osteoporosis Clinic, in an interview with MedPage Today. "The important Continue reading >>

Treatment Of Diabetic Ketoacidosis Associated With Antipsychotic Medication: Literature Review

Treatment Of Diabetic Ketoacidosis Associated With Antipsychotic Medication: Literature Review

Background The second-generation antipsychotics (SGAs) are associated with metabolic disturbances. Diabetic ketoacidosis (DKA) is a rare, but potentially fatal sign of acute glucose metabolism dysregulation, which may be associated with the use of SGAs. This study aims to review published reports of patients with schizophrenia and antipsychotic drug–associated DKA, focusing on the effective management of both conditions. Methods Using a predefined search strategy, we searched PubMed and EMBASE from their inception to July 2016. The search terms were related to “diabetic ketoacidosis” and “antipsychotic medication.” Case reports, case series, and reviews of case series written in English language were included in the review. Results Sixty-five reports were analyzed. In most patients who developed antipsychotic-associated DKA, 1 or more suspected antipsychotic medications were discontinued. In 5 cases, a rechallenge test was trialed, and in only 1 case, it resulted in the elevation of blood glucose. The majority was subsequently treated with a different SGA in combination with insulin/oral hypoglycemic agents; although approximately a third of patients had a complete resolution of symptoms or could control diabetes with diet only at the point of discharge. Conclusions Patients taking antipsychotic medications should be regularly screened for insulin resistance and educated about potential complications of antipsychotic medications. This will allow clinicians to individualize treatment decisions and reduce iatrogenic contribution to morbidity and mortality. To achieve best treatment outcomes, antipsychotic-induced DKA should be treated jointly by psychiatry and endocrinology teams. Continue reading >>

Effect Of Glargine On Recovery Of Patients With Diabetic Ketoacidosis

Effect Of Glargine On Recovery Of Patients With Diabetic Ketoacidosis

Therapy change decreased recovery time, incidence of hypoglycemia and hypokalemia… Diabetes ketoacidosis is an emergency situation caused by acute high blood glucose concentration, which may be correlated with both type 1 and 2 diabetes. The current treatment for diabetic ketoacidosis is injection of rapid-acting regular insulin. The preferred protocol is intravenous infusion. However, intravenous regular insulin has a short half-life and requires an infusion pump. Long-acting insulin, such as glargine, has an onset of action is about an hour and is stable for 24 hours. Given the duration of action of glargine, it seems that adding long-acting insulin to standard therapy improves the recovery of the patients. The aim of the present study was to evaluate the effects of glargine on the recovery of patients with diabetic ketoacidosis. The study was designed as a randomized controlled study, which consisted of 40 patients with diabetic ketoacidosis. Both groups were administered standard therapy for diabetic ketoacidosis. The experimental group received 0.4 units/kg of glargine within three hours of the start of intravenous infusion. The results showed that the average duration of acidosis correction time and recovery from diabetic ketoacidosis was 13.77±6.10 and 16.91±6.49 h in the experimental and control groups, respectively (p=0.123). The average dosage of regular insulin until recovery from diabetic ketoacidosis was 84.8±45.6 in the experimental group and 116.5±91.6 units in control groups (p=0.17). Hypokalemia happened in three patients in the experimental group and four patients in control groups. In 35% of models in the experimental group and 51% in control group blood glucose was greater than 10 mmol/l for 24 h after starting the insulin infusion (p=0.046). T Continue reading >>

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