SGLT2 inhibitors and diabetic ketoacidosis: PRAC makes recommendations to minimise risk to patients

Last Updated on

February 14, 2016 – Diabetic ketoacidosis is a serious complication of diabetes caused by low insulin levels. Rare cases of this condition, including life-threatening ones, have occurred in patients taking SGLT2 inhibitors for type 2 diabetes and a number of these cases have been atypical, with patients not having blood sugar levels as high as expected. An atypical presentation of diabetic ketoacidosis can delay diagnosis and treatment. Healthcare professionals should therefore consider the possibility of diabetic ketoacidosis in patients taking SGLT2 inhibitors who have symptoms consistent with the condition even if blood sugar levels are not high.

There are currently three SGLT2 inhibitors authorised in the European Union (EU), namely canagliflozin, dapagliflozin and empagliflozin. SGLT2 Inhibitors )Sodium-glucose co-transporter-2 (SGLT2) inhibitors block a protein in the kidneys called SGLT2, which absorbs glucose back from the urine into the bloodstream as the blood is filtered in the kidneys. By blocking the action of SGLT2, these medicines cause more glucose to be removed through the urine, thereby reducing the levels of glucose in the blood. Throughout the EU, they are available (alone or in combination with metformin) under the following trade names: Ebymect (Dapagliflozin/Metformin),  Edistride (Dapagliflozin),  Forxiga (Dapagliflozin), Invokana (Canagliflozin), Jardiance (Empagliflozin), Synjardy (Empagliflozin/Metformin), Vokanamet (Canagliflozin/Metformin) and Xigduo (Dapagliflozin/Metformin).

The European Medicine Agency (EMA)’s Pharmacovigilance Risk Assessment Committee (PRAC) has finalised a review of these SGLT2 inhibitors and has made recommendations to minimise the risk of diabetic ketoacidosis. Patients taking any of these medicines should be aware of the symptoms of diabetic ketoacidosis, including rapid weight loss, nausea or vomiting, stomach pain, excessive thirst, fast and deep breathing, confusion, unusual sleepiness or tiredness, a sweet smell to the breath, a sweet or metallic taste in the mouth, or a different odour to urine or sweat.

Patients should contact their healthcare professional if they have any of these symptoms. If diabetic ketoacidosis is suspected or confirmed, treatment should be stopped immediately and should not be re-started unless another cause for the ketoacidosis is identified and resolved. Moreover, healthcare professionals should exercise caution in patients with risk factors for ketoacidosis and inform patients of the risk factors. These include low reserve of insulin-secreting cells, conditions that restrict food intake or can lead to severe dehydration, a sudden reduction in insulin or an increased requirement for insulin due to illness, surgery or alcohol abuse. In addition, the PRAC recommended temporarily stopping SGLT2-inhibitor treatment in patients in hospital for major surgical procedures or due to serious illness.

Overall, and in spite of the dangers of the occurrence of diabetic ketoacidosis in some patients, the agency beliefs the benefits of SGLT2 inhibitors continue to outweigh their risks in the treatment of type 2 diabetes. The PRAC reminds healthcare professionals that these medicines are not authorised for treating type 1 diabetes, noting that some cases of ketoacidosis had occurred with off-label use.

Similarly to EMA’s PRAC, the FDA has recently added diabetic ketoacidosis to the Warnings Sections of the drug labels for the SGLT2 inhibitor class of drugs on the market in the US (Thasso Post posted about this). Medicines approved by the FDA in the SGLT2 inhibitor class include Canagliflozin (Invokana),  Canagliflozin / Metformin (Invokamet), Dapagliflozin (Farxiga), Dapaglifloxin / Metformin (Xigduo), Empagliflozin (Jardiance), Empagliflozin / Metformin (Synjardi), and Empagliflozin / Linagliptin (Glyxambi).

Tags: , , , , , , , , , , , , , ,
About the Author
Joseph Gut - thasso Ph.D.; Professor in Pharmacology and Toxicology. Senior expert in theragenomic and personalized medicine and individualized drug safety. Senior expert in pharmaco- and toxicogenetics. Senior expert in human safety of drugs, chemicals, environmental pollutants, and dietary ingredients.

Your opinion

Comment

No comments yet

thasso: conditions

thasso: tweets

thasso post: magazine

View my Flipboard Magazine.

thasso: categories

thasso: archives

thasso: simple chat

You must be a registered user to participate in this chat.

  • Sickle cell anemia is an inherited form of anemia February 28, 2020
    It's important to know the the symptoms, causes, and treatment of sickle cell anemia, an inherited blood disorder that, in the United States, is more common among African Americans.
  • Scientists discover three genes associated with fatal lung disease February 28, 2020
    Researchers at the Universities of Leicester and Nottingham have discovered parts of the DNA that put some people at higher risk of an incurable lung disease called idiopathic pulmonary fibrosis (IPF). The findings are published in the American Journal of Respiratory and Critical Care Medicine today, after an earlier version was posted online in November […]
  • An understudied cause of cancer: Mutations in regulators of cell signaling February 28, 2020
    Mutations in a vital class of regulatory molecules are an underappreciated cause of cancer because they impair the function of "G" proteins, a versatile and vast family of signaling switches that underlie innumerable biological facets of life itself.
  • Could new discovery play a role in diagnosing Alzheimer's earlier? February 27, 2020
    Scientists have detected that a previously overlooked gene behavior could potentially lead to a new way to diagnose Alzheimer's earlier.
  • Huntington's disease-causing DNA repeat mutations reversed in the lab February 27, 2020
    Neurodegenerative diseases, like Huntington's disease and myotonic dystrophy, are often referred to as DNA repeat diseases, named because of long repeated sequences in the DNA of patients. Increasing repeat expansion length in the affected tissues contribute to earlier age of disease onset and worsen the progression and severity of the disease over time.
  • Researchers announce progress in developing an accurate, noninvasive urine test for prostate cancer February 28, 2020
    Researchers at the Johns Hopkins Kimmel Cancer Center have made significant progress toward development of a simple, noninvasive liquid biopsy test that detects prostate cancer from RNA and other specific metabolic chemicals in the urine.
  • Anomalies in structure of polyvalent metal melts explained February 28, 2020
    Metals and their alloys are the main structural materials of modern civilization. The properties of metal melts are well studied. However, according to Anatoly Mokshin, one of the co-authors of the publication, Chair of the Department of Computational Physics at Kazan Federal University, for more than 25 years, scientists from all over the world have […]
  • New platform for engineering ribosomes to 'cook new cuisines' February 28, 2020
    Researchers have created a method for cell-free synthesis and evolution of new ribosomes that can specialize in the synthesis of functional materials and therapeutics.
  • Cartilage cells, chromosomes and DNA preserved in 75-million-year-old baby duck-billed dinosaur February 28, 2020
    In a paper published online in National Science Review, an international team of scientists present evidence of fossilized cell nuclei and chromosomes within preserved cartilage in a baby duck-billed dinosaur. This dinosaur belongs to Hypacrosaurus and comes from a nesting ground discovered in 1988 by paleontologist Jack Horner in Late Cretaceous sediments of Northwest Montana.
  • Gene therapy generates new neurons to treat Huntington's disease February 28, 2020
    Huntington's disease (HD) is a rare disease with chorea movement and caused by Huntingtin (Htt) gene mutation and neurodegeneration. A research group led by Dr. Gong Chen has developed a novel gene therapy to regenerate functional new neurons in mouse models of HD. The work has been published in Nature Communications on February 27, 2020.
Top