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Sglt2 Inhibitors And Dka

Sglt2 Inhibitors And Diabetic Ketoacidosis: Data From The Fda Adverse Event Reporting System.

Sglt2 Inhibitors And Diabetic Ketoacidosis: Data From The Fda Adverse Event Reporting System.

SGLT2 inhibitors and diabetic ketoacidosis: data from the FDA Adverse Event Reporting System. Department of Medicine, University of Padova, Via Giustiniani 2, 35128, Padova, Italy. [email protected] Department of Medicine, University of Padova, Via Giustiniani 2, 35128, Padova, Italy. Diabetologia. 2017 Aug;60(8):1385-1389. doi: 10.1007/s00125-017-4301-8. Epub 2017 May 12. AIMS/HYPOTHESIS: Sodium-glucose co-transporter-2 inhibitors (SGLT2i) are indicated for the treatment of type 2 diabetes and may also improve glucose control in type 1 diabetes. In 2015, regulatory agencies warned that SGLT2i may favour diabetic ketoacidosis (DKA). We provide a detailed analysis of DKA reports in which an SGLT2i was listed among suspect or concomitant drugs in the US Food and Drug Administration Adverse Event Reporting System (FAERS). METHODS: We first analysed the entire public FAERS up to September (third quarter [Q3]) 2016 to extract the number of reports, background indications and concomitant medications, and to calculate proportional reporting ratios (PRRs) and safety signals. We then mined single FAERS files from the first quarter (Q1) of 2014 to 2016 Q3 to obtain detailed information on DKA reports. RESULTS: The FAERS database contains >2500 DKA reports in which SGLT2i are listed as suspect or concomitant drugs. The PRR of DKA in reports including vs those not including an SGLT2i and having a diabetes indication was 7.9 (95% CI 7.5, 8.4) and was higher for type 1 diabetes. Several concomitant conditions were less prevalent in DKA reports with SGLT2i vs DKA reports filed for other drugs. A detailed analysis of 2397 DKA reports for SGLT2i from 2014 Q1 to 2016 Q3 revealed a predominance of women, an extremely wide range of age and body weight, and a highly variable durat Continue reading >>

New Study Links Sglt2 Inhibitors To Increased Risk Of Diabetic Ketoacidosis

New Study Links Sglt2 Inhibitors To Increased Risk Of Diabetic Ketoacidosis

New study links SGLT2 inhibitors to increased risk of diabetic ketoacidosis New study links SGLT2 inhibitors to increased risk of diabetic ketoacidosis Benefits of metformin may involve gut bacteria 23 May 2017 The drug class SGLT2 inhibitors have again been linked with an increased risk of diabetic ketoacidosis (DKA) in a new study. SGLT2 inhibitors have been approved to treat type 2 diabetes in the UK since 2013, but regular links with DKA , a dangerous short-term complication of diabetes if left untreated, have persisted. In 2015 the US Food and Drug Administration (FDA) issued a warning about the drugs' association with DKA, and the Medicines and Healthcare Products Regulatory Agency last year urged healthcare professionals to test for raised ketones in patients with DKA symptoms, even if their blood glucose levels were near normal. In a new study scientists from Brigham and Women's Hospital found that patients treated with SGLT2s are twice as likely to experience DKA compared to another class of diabetes medication . However, the researchers stressed that this risk is still very rare: around one in every 1,000 patients will take an SGLT2 inhibitor will experience DKA. A total of 40,000 patients taking SGLT2 inhibitors were reviewed by the researchers, and compared to patients who took a different type of medication, DPP4 inhibitors . After 180 days, 55 SGLT2-treated patients had experienced DKA, compared to 26 of the DPP4 group. Lead author Dr Michael Fralik said that while DKA is uncommon amongst SGLT2 patients, doctors need to be on the lookout for signs and symptoms of DKA among patients. These symptoms include dehydration , rapid heartbeat and vomiting. "This is a side effect that's usually seen in patients with type 1 diabetes [...] - not type 2 diabetes - so Continue reading >>

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Get Unlimited Access On Medscape.

You’ve become the New York Times and the Wall Street Journal of medicine. A must-read every morning. ” Continue reading >>

Report Compiles Data On Diabetic Ketoacidosis With Sglt2 Inhibitors

Report Compiles Data On Diabetic Ketoacidosis With Sglt2 Inhibitors

Report Compiles Data on Diabetic Ketoacidosis With SGLT2 Inhibitors While rare, diabetic ketoacidosis occurs overwhelmingly in patients taking SGLT2 inhibitors with type 2 diabetes, according to the analysis from 3 North Carolina medical schools. A data analysis in Diabetes Care finds that diabetic ketoacidosis (DKA) in patients taking sodium glucose co-transporter-2 (SGLT2) inhibitors occurs most often among patients taking the drug for type 2 diabetes (T2D), the condition for which they are FDA approved. The report, using data from Wake Forest School of Medicine, the University of North Carolina School of Medicine, and Duke University School of Medicine, tries to shed light on which patients are at risk for DKA while taking the drugs, which have quickly become one of the most prescribed second-line therapies for T2D. DKA occurs when the body produces high levels of blood acids called ketones. When the body lacks enough insulin, it begins to break down fat as fuel, causing ketones to build up in the blood. SGLT2 inhibitors work by causing the body to excrete excess glucose in the urine. SGLT2 inhibitors are also being studied in patients with type 1 diabetes (T1D), and the researchers state that some of the early reports of DKA occurred in off-label usage with this population. But the vast majority of cases, though rare, occur in patients with T2D. The analysis of the 3 North Carolina medical schools found this to be true in 74% of the cases in its records. In June, the FDA strengthened an earlier warning about the risk of DKA for the drug class. This new analysis found 39 cases of DKA among 11,197 people with prescriptions for SGLT2 inhibitors. Of these, 26 patients had glucose 300 mg/dL, with a mean glucose of 266 mg/dL. Symptoms reported included nausea and vomitin Continue reading >>

Sglt2 Inhibitors And Dka In People With Type 1 Diabetes

Sglt2 Inhibitors And Dka In People With Type 1 Diabetes

SGLT2 Inhibitors and DKA in People With Type 1 Diabetes Treating type 1 diabetes with insulin alone can be a challenge. One fairly new class of drugs, SGLT2 inhibitors, appears to be an effective add-on treatment. It reduces blood glucose levels, body weight, and the amount of insulin patients need. Also, it does not increase the frequency ofhypoglycemia(low blood glucose levels) in people with either type 1 or type 2 diabetes. However, the drug may increase the risk of diabetic ketoacidosis (DKA), a dangerous form of extremehyperglycemia(high blood glucose levels) that can lead tocomaor even death. How real is that risk? A total 351 people with poorly controlled type 1 diabetes signed up for the study. All either took multiple daily injections of insulin or used an insulin pump, which continuously delivers insulin under the skin. The participants were randomly assigned to one of two groups for the 18-week study. One group took the study drug canagliflozin, an SGLT2 inhibitor, at 100 or 300 mg once a day. The other group was given a placebo, which resembled the treatment pill but had no active ingredients. The goal: to determine which group had a higher number of participants who experienced DKA. Canagliflozin, an SGLT2 inhibitor, appears to boost the risk of serious DKA, at least when taken at the higher dose. However, the patients monitored themselves for ketones throughout the study. That means it is possible that some of them made mistakes, which could have affected the results of the study. If you take canagliflozin, be aware of the potential risks and know how to monitor yourself for any changes in your ketone levels. Talk to your doctor about these concerns and be aware of the symptoms of DKA and the circumstances in which it is most likely to occur. Diabetic Ke Continue reading >>

Sglt2 Inhibitors Double The Risk For Diabetic Ketoacidosis. N Engl J Med

Sglt2 Inhibitors Double The Risk For Diabetic Ketoacidosis. N Engl J Med

SGLT2 Inhibitors Double the Risk for Diabetic Ketoacidosis. N Engl J Med The risk of developing diabetic ketoacidosis (DKA) among type 2 diabetes patients initiating a sodiumglucose cotransporter 2 (SGLT2) inhibitor medication is about double that seen among patients starting a dipeptidyl peptidase-4 (DPP-4) inhibitor, but the overall risk is still low, new research suggests. Findings from the largest study conducted to date to investigate the issue werepublishedas a research letter in the June 8 issue of theNew England Journal of Medicineby Michael Fralick, MD, and colleagues at the Brigham and Women's Hospital, Boston, Massachusetts. "We found a doubling in the risk of DKA, which sounds frightening, but the absolute risk is quite small....I still think this is a very good class of medications and for certain patients will continue to be. Now we just have a little more information to add to the discussion when the risks and benefits are being considered," Dr Fralick toldMedscape Medical News. He estimates that between 5 and 8 patients per 1000 initiating SGLT2 inhibitors will develop DKA. And he advisesthat patients be monitored for signs of DKA or full information to thew patients of the symtoms of DKA to seek help if DKA appears after starting on SGLT2 inhibitors, noting, "This is something that can happen relatively quickly, so that's why I think it's important right after patients are started on these drugs that they're closely monitored and the clinician considers ordering bloodwork." But overall, Dr Fralick, a general internist, supports use of the SGLT2 inhibitor class for selected patients with type 2 diabetes, given the recent results from theEmpagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients(EMPA-REG OUTCOME) study showing Continue reading >>

Sglt2 Inhibitors May Predispose To Ketoacidosis

Sglt2 Inhibitors May Predispose To Ketoacidosis

SGLT2 Inhibitors May Predispose to Ketoacidosis Diabetes, Endocrinology, and Obesity Branch (S.I.T., J.E.B., K.I.R.), National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892; Division of Diabetes, Endocrinology, and Nutrition (S.I.T.), Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland 21201 Address all correspondence and requests for reprints to: Simeon I. Taylor, MD, PhD, Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Mail Stop 1453, 9000 Rockville Pike, Bethesda, MD 20892. Search for other works by this author on: Diabetes, Endocrinology, and Obesity Branch (S.I.T., J.E.B., K.I.R.), National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892; Search for other works by this author on: Diabetes, Endocrinology, and Obesity Branch (S.I.T., J.E.B., K.I.R.), National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892; Search for other works by this author on: The Journal of Clinical Endocrinology & Metabolism, Volume 100, Issue 8, 1 August 2015, Pages 28492852, Simeon I. Taylor, Jenny E. Blau, Kristina I. Rother; SGLT2 Inhibitors May Predispose to Ketoacidosis, The Journal of Clinical Endocrinology & Metabolism, Volume 100, Issue 8, 1 August 2015, Pages 28492852, Sodium glucose cotransporter 2 (SGLT2) inhibitors are antidiabetic drugs that increase urinary excretion of glucose, thereby improving glycemic control and promoting weight loss. Since approval of the first-in-class drug in 2013, data have emerged suggesting that these drugs increase the risk of di Continue reading >>

Euglycemic Dka Secondary To Sglt2 Inhibitors

Euglycemic Dka Secondary To Sglt2 Inhibitors

Authors: Priyanka Kailash (MS-4, Campbell University School of Osteopathic Medicine), Kevin Weaver, DO (Program Director, Lehigh Valley Health Network), and Krystle Shafer, MD (Attending Physician, York Hospital) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UT Southwestern Medical Center / Parkland Memorial Hospital) and Brit Long, MD (@long_brit) A 35-year-old male with a past medical history of type 2 diabetes arrives at the Emergency Department (ED) with altered mental status, nausea, vomiting, and diffuse abdominal pain that started 10 hours ago. The patient was recently started on an SGLT2 inhibitor. On examination, the patient is tachycardic (HR 126) and tachypneic (RR 25), with normal blood pressure (110/90). He is further noted to have dry mucous membranes and poor skin turgor. Blood glucose is noted to be 140 mg/dl, serum ketones 6.2 mmol/L, and arterial pH of 6.9. The patient is diagnosed with euglycemic DKA and quickly admitted to ICU for treatment. Pathogenesis of Typical DKA Two major complications from type 1 diabetes mellitus and type 2 diabetes mellitus are diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS). DKA is typically seen in younger individuals, while HHS is typically seen in older patients(1). In the pathogenesis of typical DKA, the body experiences a starved state. Insulin deficiency (either through decreased production or decrease sensitivity) leads to the inactivation of GLUT4 receptors on cells. GLUT4 receptors function to help transport glucose molecules into cells so that it can be converted into energy. Without GLUT4 receptor activation, the glucose entry into cells remains shut. Thus, the cells start to experience a starved state. To compensate, the body activates an alternative energy pathway Continue reading >>

Euglycemic Diabetic Ketoacidosis: The Clinical Concern Of Sglt2 Inhibitors

Euglycemic Diabetic Ketoacidosis: The Clinical Concern Of Sglt2 Inhibitors

Euglycemic diabetic ketoacidosis is a post market warning in patients with type 1 diabetes and type 2 diabetes treated with SGLT-2 inhibitors. We report a case of a 39-year-old obese female with presumed type 2 diabetes for seven years who presented to the emergency department with three days of nausea, vomiting, and abdominal pain. Due to previous total non-adherence with a prescribed insulin regimen, she was recently started on canagliflozin and liraglutide. The diagnosis of euDKA was missed in the initial evaluation as the blood glucose level was only 167 mg/dL. Further work up showed severe metabolic acidosis with an anion gap of 25 and positive ketones in the urine. She was treated successfully with dextrose water 5%/half normal saline and an insulin drip. As part of the work up, she tested positive for glutamic acid decarboxylase autoantibodies. Given the increasing utilization of SGLT-2 inhibitors and the fact that patients can present with near-normal glycemia, the diagnosis can be missed. Vigilance with the use of SGLT-2 inhibitors is necessary to decrease morbidity and potentially mortality particularly in patients with long-standing type 2 diabetes associated with marked β-cell insufficiency, type 1 diabetes mellitus, or latent autoimmune diabetes of adult onset. Continue reading >>

Risk Of Diabetic Ketoacidosis After Initiation Of An Sglt2 Inhibitor

Risk Of Diabetic Ketoacidosis After Initiation Of An Sglt2 Inhibitor

To the Editor: Inhibitors of sodium–glucose cotransporter 2 (SGLT2) decrease plasma glucose by blocking the reabsorption of glucose at the proximal tubule.1,2 Case reports have suggested that SGLT2 inhibitors may be associated with an increased risk of diabetic ketoacidosis, which led to a warning from the Food and Drug Administration (FDA) in May 2015.3,4 The objective of our study was to assess the risk of diabetic ketoacidosis after the initiation of an SGLT2 inhibitor. Using a large claims database of commercially insured patients in the United States (Truven MarketScan), we identified a cohort of adult patients (≥18 years of age) who had newly started treatment with either an SGLT2 inhibitor or a dipeptidyl peptidase-4 (DPP4) inhibitor between April 1, 2013, and December 31, 2014 (before the FDA warning). DPP4 inhibitors were chosen as the comparator medication because they are similarly used as a second-line treatment for diabetes but have no known association with diabetic ketoacidosis. We excluded patients with human immunodeficiency virus infection, end-stage renal disease, cancer, type 1 diabetes, or past diabetic ketoacidosis. Our primary outcome was hospitalization for diabetic ketoacidosis (using the primary position code of the International Classification of Diseases, Ninth Revision) within 180 days after the initiation of an SGLT2 inhibitor or a DPP4 inhibitor. We censored data for patients at the time that they discontinued the initial medication, had the outcome, lost insurance coverage, or died. We used 1:1 propensity-score matching to balance 46 characteristics of the patients and Cox regression to estimate hazard ratios and 95% confidence intervals for diabetic ketoacidosis within 180 days after treatment initiation. Predefined sensitivity analy Continue reading >>

Understanding Sglt2 Inhibitors' Diabetic Ketoacidosis Risk

Understanding Sglt2 Inhibitors' Diabetic Ketoacidosis Risk

Deepali Dixit, PharmD, BCPS, is a Clinical Assistant Professor at Ernest Mario School of Pharmacy and a Clinical Critical Care Pharmacist in the Medical Intensive Care Unit at Robert Wood Johnson University Hospital. Dr. Dixit has been involved in multiple committees and in leadership positions in regional and national pharmacy and organizations. Dr. Dixit's research interests include sedation and delirium in the critically ill, infectious disease, alcohol withdrawal syndrome, chronic obstructive pulmonary disease, and patient safety. This article was collaboratively written with Shannon Anthony, PharmD Candidate. In May 2015, the FDA issued a warning about the risk of developing diabetic ketoacidosis while using SGLT2 inhibitors. That December, the FDA updated the drugs’ labels to include warnings about developing ketoacidosis even with near-normal blood glucose levels.1 SGLT2 inhibitors lower blood glucose levels by decreasing renal glucose reabsorption, which increases urinary glucose excretion.2 Three drugs in this class are currently available in the United States: canagliflozin (Invokana), dapagliflozin (Farxiga), and empagliflozin (Jardiance).1 These medications are approved for managing type 2 diabetes, although they’re increasingly used off-label to treat type 1 diabetes (T1D), and trials are currently being conducted to evaluate their efficacy for this potential indication.3 Diabetic ketoacidosis (DKA) develops most frequently in T1D patients secondary to omission or decreased dosage of insulin, acute illness, or a recent surgical procedure.4 The typical clinical presentation includes hyperglycemia (>250mg/dL), anion-gap acidosis, and elevated plasma and urine ketones.3 Early diagnosis and management of ketoacidosis is vital. The cornerstone DKA treatment Continue reading >>

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Sglt2 Inhibitors And Diabetic Ketoacidosis: What's Behind The Fda Warning

Sglt2 Inhibitors And Diabetic Ketoacidosis: What's Behind The Fda Warning

With commentary by Yehuda Handelsman, MD, FACP, FACE, FNLA, an endocrinologist in private practice in Tarzana, CA, Medical Director and Principal Investigator of the Metabolic Institute of America and President of the American College of Endocrinology People with diabetes who take blood sugar-lowering drugs called SGLT2 inhibitors were recently warned by the U.S. Food and Drug Administration (FDA) that they should watch for signs of a life-threatening condition called diabetic ketoacidosis. canagliflozin (Invokana) dapagliflozin (Farxiga) empagliflozin (Jardiance) as well as the combination pills: canagliflozin plus metformin (Invokamet) dapagliflozin plus metformin extended-release (Xigduo XR) empagliflozin plus linagliptin (Glyxambi). “Diabetic ketoacidosis (DKA) can be deadly,” says Amy Hess-Fischl, MS, RD, LDN, BC-ADM, CDE, an advanced practice dietitian at the University of Chicago Kovler Diabetes Center and a member of EndocrineWeb’s advisory board. “DKA is usually more of a concern for people with type 1 diabetes, but this warning is for people with type 2 diabetes who are taking the SGLT2 inhibitors, as well as people with type 1 diabetes who take these medications off label. DKA — dangerously high acid levels in the bloodstream — happens when your body breaks down fat instead of glucose for energy, releasing acidic compounds called ketones. Early symptoms include thirst, frequent urination and sweet, fruity breath, Hess-Fischl says. You may feel tired and confused, and develop nausea, stomach pain, vomiting and difficulty breathing. “If you notice symptoms, call your doctor immediately. But if you’re vomiting, can’t catch your breath or are concerned, go to the emergency room,” she says. Putting the Risk in Perspective The FDA warning, relea Continue reading >>

Sglt2 Inhibitors: Updated Advice On The Risk Of Diabetic Ketoacidosis

Sglt2 Inhibitors: Updated Advice On The Risk Of Diabetic Ketoacidosis

Advice for healthcare professionals: When treating patients who are taking a sodium-glucose co-transporter 2 (SGLT2) inhibitor (canagliflozin, dapagliflozin, or empagliflozin): inform them of the signs and symptoms of diabetic ketoacidosis (DKA) – see below – and advise them to seek immediate medical advice if they develop any of these discuss the risk factors for DKA with patients (see below) discontinue treatment with the SGLT2 inhibitor immediately if DKA is suspected or diagnosed do not restart treatment with any SGLT2 inhibitor in patients who experienced DKA during use, unless another cause for DKA was identified and resolved interrupt treatment with the SGLT2 inhibitor in patients who are hospitalised for major surgery or acute serious illnesses; treatment may be restarted once the patient’s condition has stabilised Reports of diabetic acidosis EU medicines regulators have completed a review of DKA associated with SGLT2 inhibitor treatment; this article summarises the review’s recommendations. We published preliminary advice on this in June 2015. SGLT2 inhibitors are licensed for use in adults with type 2 diabetes to improve glycaemic control. Serious, life-threatening, and fatal cases of DKA have been reported in patients taking an SGLT2 inhibitor (canagliflozin, dapagliflozin, or empagliflozin). The EU review concluded that this side effect is rare (affecting between 1 in 1000 and 1 in 10,000 patients). Up to 26 February 2016, we had received 118 Yellow Card reports of DKA and associated reactions in patients taking an SGLT2 inhibitor in the UK. In several cases, blood glucose levels were only moderately elevated (eg <14mmol/L)—representing an atypical presentation for DKA, which could delay diagnosis and treatment. Therefore inform patients of the si Continue reading >>

Euglycemic Diabetic Ketoacidosis: A Predictable, Detectable, And Preventable Safety Concern With Sglt2 Inhibitors

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 (canagliflozin, dapagliflozin, and empagliflozin) to evaluate the risk of DKA in T2D (2). The EMA announcement claimed that as of May 2015 a total of 101 cases of DKA have been reported worldwide in EudraVigilance in T2D patients treated with SGLT2 inhibitors, with an estimated exposure over 0.5 million patient-years. No clinical details were provided except for the mention that “all cases were serious and some required hospitalisation. Although [DKA] is usually accompanied by high blood sugar levels, in a number of these reports blood sugar levels were only moderately increased” (2). Wit Continue reading >>

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