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Why Is Metformin Contraindicated In Ketoacidosis

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 >>

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 >>

Management Of Persistent Hyperglycemia In Type 2 Diabetes Mellitus

Management Of Persistent Hyperglycemia In Type 2 Diabetes Mellitus

The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc. All topics are updated as new evidence becomes available and our peer review process is complete. INTRODUCTION — Initial treatment of patients with type 2 diabetes mellitus includes education, with emphasis on lifestyle changes including diet, exercise, and weight reduction when appropriate. Monotherapy with metformin is indicated for most patients, and insulin may be indicated for initial treatment for some [1]. Although several studies have noted remissions of type 2 diabetes mellitus that may last several years, most patients require continuous treatment in order to maintain normal or near-normal glycemia. Bariatric surgical procedures in obese patients that result in major weight loss have been shown to lead to remission in a substantial fraction of patients. Regardless of the initial response to therapy, the natural history of most patients with type 2 diabetes is for blood glucose concentrations to rise gradually with time. Treatment for hyperglycemia that fails to respond to initial monotherapy and long-term pharmacologic therapy in type 2 diabetes is reviewed here. Options for initial therapy and other therapeutic issues in diabetes management, such as the frequency of monitoring and evaluation for microvascular and macrovascular complications, are discussed separately. (See "Initial management of blood glucose in adults with type 2 diabetes mellitus" and "Overview of medical care in adults with diabetes mellitus". Continue reading >>

Pioglitazone/metformin

Pioglitazone/metformin

Pioglitazone/metformin (also known by the brand names Actoplus Met, Piomet and Politor) is combination of two oral diabetes medications pioglitazone and metformin. The two oral antihyperglycemic agents with different mechanisms of action are used to improve glycemic control in patients with diabetes mellitus type 2. Mechanisms[edit] Pioglitazone is a member of the thiazolidinedione class, it decreases insulin resistance in the periphery and in the liver resulting in increased insulin dependent glucose disposal and decreased hepatic glucose output. Metformin is a member of the biguanide class, improves glucose tolerance in patients with type 2 diabetes, lowering both basal and postprandial plasma glucose. Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose and improves insulin sensitivity by increasing peripheral glucose uptake and utilization. Indication[edit] Pioglitazone/metformin is indicated as an adjunct to diet and exercise: To improve glycemic control in patients with type 2 diabetes, or For patients who are already treated with a separate combination of pioglitazone and metformin, For patients whose diabetes is not adequately controlled with metformin alone, or For patients who have initially responded to pioglitazone alone and require additional glycemic control. Dosage and administration[edit] Recommended dose[edit] Use of antihyperglycemic agents in the management of type 2 diabetes should be individualized on the basis of effectiveness and tolerability. Pioglitazone/metformin should be given with meals; the initial starting dose is either the 15 mg/500 mg or 15 mg/850 mg tablet strength once or twice daily, and gradually titrated after assessing adequacy of therapeutic response, while not exceeding the maximum recommend 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 >>

Call Diabetes Access Support

Call Diabetes Access Support

WARNING: LACTIC ACIDOSIS 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 XIGDUO XR and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended. Contraindications Warnings and Precautions Hypotension: Dapagliflozin causes intravascular volume contraction, and symptomatic hypotension can occur. Assess and correct volume status before initiating XIGDUO XR in patients with impaired renal function, elderly patients, or patients on loop diuretics. Monitor for hypotension. Ketoacidosis has been reported in patients with type 1 and type 2 diabetes receiving dapagliflozin. Some cases were fatal. Assess patients who present with signs and symptoms of metabolic acidosis for ketoacidosis, regardless of blood glucose level. If suspected, discontinue XIGDUO XR, evaluate and treat promptly. Before initiating XIGDUO XR, consider risk factors for ketoacidosis. Patients on XIGDUO XR may require monitoring and temporary discontinuation in situations known to predispose to ketoacidosis. Acut 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 >>

Hyperglycaemic Crises And Lactic Acidosis In Diabetes Mellitus

Hyperglycaemic Crises And Lactic Acidosis In Diabetes Mellitus

Hyperglycaemic crises are discussed together followed by a separate section on lactic acidosis. DIABETIC KETOACIDOSIS (DKA) AND HYPERGLYCAEMIC HYPEROSMOLAR STATE (HHS) Definitions DKA has no universally agreed definition. Alberti proposed the working definition of “severe uncontrolled diabetes requiring emergency treatment with insulin and intravenous fluids and with a blood ketone body concentration of >5 mmol/l”.1 Given the limited availability of blood ketone body assays, a more pragmatic definition comprising a metabolic acidosis (pH <7.3), plasma bicarbonate <15 mmol/l, plasma glucose >13.9 mmol/l, and urine ketostix reaction ++ or plasma ketostix ⩾ + may be more workable in clinical practice.2 Classifying the severity of diabetic ketoacidosis is desirable, since it may assist in determining the management and monitoring of the patient. Such a classification is based on the severity of acidosis (table 1). A caveat to this approach is that the presence of an intercurrent illness, that may not necessarily affect the level of acidosis, may markedly affect outcome: a recent study showed that the two most important factors predicting mortality in DKA were severe intercurrent illness and pH <7.0.3 HHS replaces the older terms, “hyperglycaemic hyperosmolar non-ketotic coma” and “hyperglycaemic hyperosmolar non-ketotic state”, because alterations of sensoria may be present without coma, and mild to moderate ketosis is commonly present in this state.4,5 Definitions vary according to the degree of hyperglycaemia and elevation of osmolality required. Table 1 summarises the definition of Kitabchi et al.5 Epidemiology The annual incidence of DKA among subjects with type 1 diabetes is between 1% and 5% in European and American series6–10 and this incidence appear 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 >>

Metformin: An Old But Still The Best Treatment For Type 2 Diabetes

Metformin: An Old But Still The Best Treatment For Type 2 Diabetes

Abstract The management of T2DM requires aggressive treatment to achieve glycemic and cardiovascular risk factor goals. In this setting, metformin, an old and widely accepted first line agent, stands out not only for its antihyperglycemic properties but also for its effects beyond glycemic control such as improvements in endothelial dysfunction, hemostasis and oxidative stress, insulin resistance, lipid profiles, and fat redistribution. These properties may have contributed to the decrease of adverse cardiovascular outcomes otherwise not attributable to metformin’s mere antihyperglycemic effects. Several other classes of oral antidiabetic agents have been recently launched, introducing the need to evaluate the role of metformin as initial therapy and in combination with these newer drugs. There is increasing evidence from in vivo and in vitro studies supporting its anti-proliferative role in cancer and possibly a neuroprotective effect. Metformin’s negligible risk of hypoglycemia in monotherapy and few drug interactions of clinical relevance give this drug a high safety profile. The tolerability of metformin may be improved by using an appropiate dose titration, starting with low doses, so that side-effects can be minimized or by switching to an extended release form. We reviewed the role of metformin in the treatment of patients with type 2 diabetes and describe the additional benefits beyond its glycemic effect. We also discuss its potential role for a variety of insulin resistant and pre-diabetic states, obesity, metabolic abnormalities associated with HIV disease, gestational diabetes, cancer, and neuroprotection. Introduction The discovery of metformin began with the synthesis of galegine-like compounds derived from Gallega officinalis, a plant traditionally em 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 >>

Metformin‐associated Lactic Acidosis In A Patient With Liver Disease

Metformin‐associated Lactic Acidosis In A Patient With Liver Disease

Sir, Metformin is an orally active biguanide, and was found to reduce mortality and complications in obese diabetic patients in the UK Prospective Diabetes Study.1 As a result, the drug is widely used as first‐line therapy for patients with obesity and type 2 diabetes. We would like to remind prescribers of a rare, but commonly fatal complication of metformin therapy in patients with liver or renal disease. A 40‐year‐old Gujerati man was admitted through accident and emergency. On admission, little history was available from the patient, and no corroborative history was available, apart from the fact that he was diabetic and on metformin. He was short of breath at rest, with oxygen saturation of 84% on air, and had a Glasgow Coma Score of 13/15. Capillary blood glucose was 1.7 mmol/l. Arterial blood gas analysis on 60% oxygen revealed severe metabolic acidosis: pH 6.62, pCO2 8.3 kPa, pO2 47.8 kPa, base excess −31.2, bicarbonate 6.4 mmol/l, anion gap 37 mmol/l. Serum lactate was extremely high at >20 mmol/l. He had a low urea of 2.4 mmol/l, normal creatinine of 63 µmol/l, a raised aspartate transaminase (110 IU/l, NR 10–50), bilirubin (64 µmol/l, NR 2–17) and alkaline phosphatase (323 IU/l, NR 40–135). He had a macrocytic anaemia (haemoglobin 9.7 g/dl, NR 13.0–17.0; MCV 99.0 fl, NR 76.0–96.0), and deranged clotting (PT 30 s, control 12 s; KPTT 65 s, control 35 s), but normal platelet count (152×109/l, NR 135–450). Hypoglycaemia was confirmed by a venous plasma glucose of 1.9 mmol/l. On review of his medical notes, he had been diagnosed with type 2 diabetes 3 years prior to admission. He had not been seen at diabetic clinic for over 2 years, when his diabetes was well controlled with metformin 850 mg twice daily. Eighteen months previously, he was a Continue reading >>

Hypoglycemic Drugs

Hypoglycemic Drugs

RARELY PRESCRIBED (lower potency, greater toxicity) Keywords 2nd Generation Sulfonylureas: Glimepiride, Glipizide & Glyburide Fewer drug interactions, & side effects, more commonly prescribed Repaglinide 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 Poems Patient Oriented Evidence That Matters

Diabetes Poems Patient Oriented Evidence That Matters

Diabetes Management To prevent or reduce the progression of microvascular and macrovascular complications, recommended diabetes management encompasses both metabolic control and control of cardiovascular risk factors (Snow et al, 2004). The need for good glycaemic control is supported by the Diabetes Control and Complications Trial in type 1 diabetes and the United Kingdom Prospective Diabetes study in type 2 diabetes. In these studies, tight blood sugar control reduced microvascular complications such as nephropathy and retinopathy but had little effect on macrovascular outcomes (Snow et al, 2004). Oral HypoglycaemicAgents Antidiabetic treatment is not a substitute for a healthy diet and exercise, which should always be encouraged. In people whose blood glucose is inadequately controlled (HbA1C target 6.5-7.5% (NICE, 2002)) using lifestyle interventions alone, oral hypoglycaemic therapy can be initiated. Metformin Metformin reduces hepatic glucose production and increases peripheral utilisation of glucose. There is no risk of hypoglycaemia when used alone. Lactic acidosis is the most serious adverse effect but is very rare (0.03 cases per 1000 patient years), it occurs mainly with high dose (a maximum dose of 3000mg per day can be given) and in people with renal impairment (including situations with a risk of altered renal function e.g. dehydration, severe infection, ketoacidosis, surgery, use of iodinated contrast media); or hepatic impairment, alcohol abuse, old age and heart failure (AMH, 2004). It has been proposed that metformin should be considered the optimal first line therapy for patients with type 2 diabetes as long as there are no contraindications to its use (refer table). This is based on the antihyperglycaemic effect of metformin, positive influence on a Continue reading >>

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