Sodium-glucose cotransporter-2 (SGLT2) inhibitors in Type-2 Diabetes: Risk of acute kidney injury

Last Updated on

June 16, 2016 – The sodium-glucose cotransporter 2 (SGLT2) is a protein that is encoded by the SLC5A2 gene. SGLT2 is one member of a larger family of sodium-glucose cotransporters which are sodium-dependent glucose transport proteins. SGLT2 is the major cotransporter involved in glucose reabsorption in the kidney. SGLT2 inhibitors are called gliflozins and are therapeutically useful in the treatment of type 2 diabetes. They act by inhibiting sodium/glucose cotransporter 2 (SGLT-2); their efficacy is dependent on renal excretion and in preventing  glucose from going into blood circulation by promoting glucosuria. The mechanism of action is insulin independent. Gliflozins enhance glycemic control as well as reduce body weight and systolic and diastolic blood pressure.

To date in the US, three gliflozins have been approved by the American Food & Drug Administration (FDA), namely dapagliflozin, canagliflozin and empagliflozin. They are on the market available as Canagliflozin (Invokana), Canagliflozin / Metformin (Invokamet), Dapagliflozin (Farxiga), Dapagliflozin / Metformin (Xigduo XR), Empagliflozin (Jardiance), Empaglifozin / Linagliptin (Glyxambi), and Empagliflozin /Metformin (Synjardi). The medicines containing any one of the three gliflozins may lead to ketoacidosis. Recently, investigation by the FDA and the European Medicines Agency (EMA) on the dangers of bone fractures and amputations of peripheral in connection with the use of canagliflozin-containing medicines have been launched.

Acute Kidney Injury IIHere, in a new Safety Alert, the FDA has strengthened the existing warning about the risk of acute kidney injury for Canagliflozin (Invokana), Canagliflozin / Metformin (Invokamet), Dapagliflozin (Farxiga), Dapagliflozin / Metformin (Xigduo XR).  Based on recent reports, FDA has revised the warnings in the drug labels to include information about acute kidney injury and added recommendations to minimize this risk.

This action is based on the fact that from March 2013, when Canagliflozin (Invokana) was approved, to October 2015, FDA received reports of 101 confirmable cases of acute kidney injury, some requiring hospitalization and dialysis, with canagliflozin- or dapagliflozin-containing medicines (see the data summary in the  Drug Safety Communication).  This number includes only reports submitted to FDA, so there are likely additional cases about which we are unaware.

Health care professionals should consider factors that may predispose patients to acute kidney injury prior to starting them on canagliflozin- or dapagliflozin-containg medicines. These include decreased blood volume; chronic kidney insufficiency; congestive heart failure; and taking other medications such as diuretics, blood pressure medicines called angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), and nonsteroidal anti-inflammatory drugs (NSAIDs). They should assess kidney function prior to starting these medicines and monitor periodically thereafter. If acute kidney injury occurs, the drugs should promptly be discontinued and the kidney impairment treated.

Patients should seek medical attention immediately if they experience signs and symptoms of acute kidney injury. This is a serious condition in which the kidneys suddenly stop working, causing dangerous levels of wastes to build up in the body.  Signs and symptoms of acute kidney injury may include decreased urine or swelling in the legs or feet.  Patients should not stop taking their medicine without first talking to their health care professionals.  Doing so can lead to uncontrolled blood sugar levels that can be harmful. Patients should read the Medication Guide they received with the prescription of any one of the canagliflozin- or dapagliflozin-containing medicines. The Medication Guide explains in detail the benefits and risks associated with the medicine.

 

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: newest tweets

thasso: recent comments

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.

  • New CRISPR advance may solve key quandary June 2, 2020
    A mutation unique to certain cancer tumors is a potential homing beacon for safely deploying CRISPR gene editing enzymes to disarm DNA that makes cancer cells resistant to treatment, while ignoring the gene in normal cells where it's critical to healthy function, according to a new study from ChristianaCare's Gene Editing Institute in the journal […]
  • Gene discovery in fruit flies 'opens new doors' for hearing loss cure in elderly June 2, 2020
    Scientists at UCL have discovered sets of regulatory genes, which are responsible for maintaining healthy hearing. The finding, made in fruit flies, could potentially lead to treatments for age-related hearing loss (ARHL) in humans.
  • Study reveals how a master regulator of gene transcription operates June 2, 2020
    Using targeted protein degradation technology, researchers at CeMM, the Research Center for Molecular Medicine of the Austrian Academy of Sciences, set out to understand the primary role of a key regulator of transcription, the human Mediator complex. Mediator, a 30-subunit molecular machine, was believed to be a factor that is generally required for the transcription […]
  • Genetic cause of difference in sexual development uncovered June 1, 2020
    Researchers at the Francis Crick Institute, the Institut Pasteur and their clinical collaborators have identified a cause of testicular tissue developing in people with female chromosomes.
  • The interface of genomic information with the electronic health record June 1, 2020
    Advances in genetic and genomic testing technology have not only introduced the utilization of clinical genomic information into virtually every area of medical care, this testing has become an essential tool to achieve the goal of precision medicine. As genomic data become more complex, so too must the electronic health record (EHR) evolve to provide […]
  • Piecing together the Dead Sea Scrolls with DNA evidence June 2, 2020
    Piecing together the collection of more than 25,000 fragments of ancient manuscripts known as the Dead Sea Scrolls in order to understand their meaning has remained an incredibly difficult puzzle. Now, researchers reporting in the journal Cell on June 2 have used an intriguing clue to help in this effort: DNA "fingerprints" lifted from the […]
  • Bees grooming each other can boost colony immunity June 2, 2020
    Honeybees that specialise in grooming their nestmates (allogroomers) to ward off pests play a central role in the colony, finds a new UCL and University of Florence study published in Scientific Reports.
  • Extracellular vesicles play an important role in the pathology of malaria vivax June 2, 2020
    Extracellular vesicles (EVs) play a role in the pathogenesis of malaria vivax, according to a study led by researchers from the Barcelona Institute for Global Health (ISGlobal) and the Germans Trias i Pujol Health Science Research Institute (IGTP). The findings, published in Nature Communications, indicate that EVs from P. vivax patients communicate with spleen fibroblasts […]
  • When determining sex, exceptions are the rule June 2, 2020
    Thanks to new genomic data, long-held theories on sex chromosome evolution are now being tested against empirical evidence from nature -- often with surprising results.
  • Carnegie Mellon tool automatically turns math into pictures June 2, 2020
    Some people look at an equation and see a bunch of numbers and symbols; others see beauty. Thanks to a new tool created at Carnegie Mellon University, anyone can now translate the abstractions of mathematics into beautiful and instructive illustrations. The tool enables users to create diagrams simply by typing an ordinary mathematical expression and […]
Top