Susan Cornell, PharmD, CDE, FAPhA, FAADE, describes the risks for ketoacidosis and serious urinary tract infection associated with use of SGLT2 inhibitors. This video was recorded at APhA's 2016 Annual Meeting and Exposition in Baltimore, Maryland.
Euglycemic Diabetic Ketoacidosis: A Predictable, Detectable, And Preventable Safety Concern With Sglt2 Inhibitors
The Case At Hand Recently, the U.S. Food and Drug Administration (FDA) issued a Drug Safety Communication that warns of an increased risk of diabetic ketoacidosis (DKA) with uncharacteristically mild to moderate glucose elevations (euglycemic DKA [euDKA]) associated with the use of all the approved sodium–glucose cotransporter 2 (SGLT2) inhibitors (1). This Communication was based on 20 clinical cases requiring hospitalization captured between March 2013 and June 2014 in the FDA Adverse Event Reporting System database. The scarce clinical data provided suggested that most of the DKA cases were reported in patients with type 2 diabetes (T2D), for whom this class of agents is indicated; most likely, however, they were insulin-treated patients, some with type 1 diabetes (T1D). The FDA also identified potential triggering factors such as intercurrent illness, reduced food and fluid intake, reduced insulin doses, and history of alcohol intake. The following month, at the request of the European Commission, the European Medicines Agency (EMA) announced on 12 June 2015 that the Pharmacovigilance Risk Assessment Committee has started a review of all of the three approved SGLT2 inhibitors
What is DIABETIC KETOACIDOSIS? What does DIABETIC KETOACIDOSIS mean? DIABETIC KETOACIDOSIS meaning - DIABETIC KETOACIDOSIS definition - DIABETIC KETOACIDOSIS explanation. Source: Wikipedia.org article, adapted under https://creativecommons.org/licenses/... license. SUBSCRIBE to our Google Earth flights channel - https://www.youtube.com/channel/UC6Uu... Diabetic ketoacidosis (DKA) is a potentially life-threatening complication of diabetes mellitus. Signs and symptoms may include vomiting, abdominal pain, deep gasping breathing, increased urination, weakness, confusion, and occasionally loss of consciousness. A person's breath may develop a specific smell. Onset of symptoms is usually rapid. In some cases people may not realize they previously had diabetes. DKA happens most often in those with type 1 diabetes, but can also occur in those with other types of diabetes under certain circumstances. Triggers may include infection, not taking insulin correctly, stroke, and certain medications such as steroids. DKA results from a shortage of insulin; in response the body switches to burning fatty acids which produces acidic ketone bodies. DKA is typically diagnosed when testing finds high blood sugar, low blood pH, and ketoacids in either the blood or urine. The primary treatment of DKA is with intravenous fluids and insulin. Depending on the severity, insulin may be given intravenously or by injection under the skin. Usually potassium is also needed to prevent the development of low blood potassium. Throughout treatment blood sugar and potassium levels should be regularly checked. Antibiotics may be required in those with an underlying infection. In those with severely low blood pH, sodium bicarbonate may be given; however, its use is of unclear benefit and typically not recommended. Rates of DKA vary around the world. About 4% of people with type 1 diabetes in United Kingdom develop DKA a year, while in Malaysia the condition affects about 25% a year. DKA was first described in 1886 and, until the introduction of insulin therapy in the 1920s, it was almost universally fatal. The risk of death with adequate and timely treatment is currently around 1–4%. Up to 1% of children with DKA develop a complication known as cerebral edema. The symptoms of an episode of diabetic ketoacidosis usually evolve over a period of about 24 hours. Predominant symptoms are nausea and vomiting, pronounced thirst, excessive urine production and abdominal pain that may be severe. Those who measure their glucose levels themselves may notice hyperglycemia (high blood sugar levels). In severe DKA, breathing becomes labored and of a deep, gasping character (a state referred to as "Kussmaul respiration"). The abdomen may be tender to the point that an acute abdomen may be suspected, such as acute pancreatitis, appendicitis or gastrointestinal perforation. Coffee ground vomiting (vomiting of altered blood) occurs in a minority of people; this tends to originate from erosion of the esophagus. In severe DKA, there may be confusion, lethargy, stupor or even coma (a marked decrease in the level of consciousness). On physical examination there is usually clinical evidence of dehydration, such as a dry mouth and decreased skin turgor. If the dehydration is profound enough to cause a decrease in the circulating blood volume, tachycardia (a fast heart rate) and low blood pressure may be observed. Often, a "ketotic" odor is present, which is often described as "fruity", often compared to the smell of pear drops whose scent is a ketone. If Kussmaul respiration is present, this is reflected in an increased respiratory rate.....
Euglycemic Diabetic Ketoacidosis, A Misleading Presentation Of Diabetic Ketoacidosis
Go to: Introduction Hyperglycemia and ketosis in diabetic ketoacidosis (DKA) are the result of insulin deficiency and an increase in the counterregulatory hormones glucagon, catecholamines, cortisol, and growth hormone. Three processes are mainly responsible for hyperglycemia: increased gluconeogenesis, accelerated glycogenolysis, and impaired glucose utilization by peripheral tissues. This might also be augmented by transient insulin resistance due to hormone imbalance, as well as elevated free fatty acids. DKA is most commonly precipitated by infections. Other factors include discontinuation of or inadequate insulin therapy, pancreatitis, myocardial infarction, cerebrovascular accident, and illicit drug use. The diagnostic criteria of DKA, established by the American Diabetic Association, consists of a plasma glucose of >250 mg/dL, positive urinary or serum ketones, arterial pH of <7.3, serum bicarbonate <18 mEq/L, and a high anion gap. The key diagnostic feature of DKA is elevated circulating total blood ketone concentration. Hyperglycemia is also a key diagnostic criterion of DKA; however, a wide range of plasma glucose levels can be present on admission.
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Euglycemic Diabetic Ketoacidosis Sometimes Seen With Sglt2 Inhibitors
Euglycemic Diabetic Ketoacidosis Sometimes Seen with SGLT2 Inhibitors Diabetic ketoacidosis (DKA) in patients with presenting serum blood glucose <200 mg/dL isnt common. More often, its seen in patients with type 1 diabetes in conjunction with starvation and acute illness.1 Its difficult to determine an incidence of euglycemic DKA (euDKA) among all DKA cases in the literature, given the migration of the serum glucose cutoff from 300 mg/dL to 200 mg/dL. The best estimation based on an analysis of case reports suggests an incidence anywhere between 0.8% and 7.5%.1 However, the sodium-glucose cotransporter-2 (SGLT2) inhibitors canagliflozin, dapagliflozin, and empagliflozin can apparently induce this once-rare form of DKA.2,3 SGLT2 inhibitors are a class of oral hypoglycemic drugs indicated only for type 2 diabetes. Their novel mechanism of action prevents glucose reabsorption from the proximal renal tubules, resulting in increased glucosuria and decreasing plasma glucose. SGLT2 inhibitors lower serum glucose and HBA1C levels, and even produce weight loss. However, the increased glucose concentration in the bladder is a terrific incubation environment for fungi and bacteria, so much
Prashanth Rawla1, Anantha R Vellipuram2, Sathyajit S Bandaru3 and Jeffrey Pradeep Raj4 Department of Internal Medicine, Memorial Hospital of Martinsville and Henry County, Martinsville, Virginia, USA  Texas Tech University Health Sciences Center, El Paso, Texas, USA  Senior Research Associate, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA  Department of Pharmacology, St John’s Medical Colle ...
Objective Sodiumglucose cotransporter 2 (SGLT-2) inhibitors are the most recently approved antihyperglycemic medications. We sought to describe their association with euglycemic diabetic ketoacidosis (euDKA) in hopes that it will enhance recognition of this potentially life-threatening complication. Research Design and Methods Cases identified incidentally are described. Results We identified 13 episodes of SGLT-2 inhibitorassociated euDKA or ke ...
Euglycemic Diabetic Ketoacidosis: A Review Author(s): Anar Modi , Department of Endocrinology, Diabetes & Metabolism, Cooper University Hospital, Camden, New Jersey, United States Abhinav Agrawal* , Department of Medicine, Monmouth Medical Center, 300 Second Avenue, Long Branch, New Jersey, United States Farah Morgan . Department of Endocrinology, Diabetes & Metabolism, Cooper University Hospital, Camden, New Jersey, United States Introduction: ...
Craig Cocchio, PharmD, BCPS, is an Emergency Medicine Clinical Pharmacist at Trinity Mother Frances Hospital in Tyler, Texas. Follow on Twitter @iEMPharmD and on his blog at empharmd.blogspot.com Diabetic ketoacidosis (DKA) in patients with presenting serum blood glucose <200 mg/dL isn’t common. More often, it’s seen in patients with type 1 diabetes in conjunction with starvation and acute illness.1 It’s difficult to determine an incidence ...
Tweet Diabetic ketoacidosis (DKA) is a dangerous complication faced by people with diabetes which happens when the body starts running out of insulin. DKA is most commonly associated with type 1 diabetes, however, people with type 2 diabetes that produce very little of their own insulin may also be affected. Ketoacidosis is a serious short term complication which can result in coma or even death if it is not treated quickly. Read about Diabetes a ...