Can You Spot Euglycemic DKA From SGLT-2 Inhibitors?

Written by Clay Smith

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Sodium-glucose cotransporter-2 (SGLT-2) inhibitors were associated with a threefold increased risk for diabetic ketoacidosis (DKA) compared to another drug class in patients with type 2 diabetes.

Why does this matter?
SGLT-2 drugs reduce cardiovascular, renal, and mortality outcomes in patient with type 2 diabetes, yet there have been case reports of euglycemic DKA. Common SGLT-2 agents are canagliflozin, dapagliflozin, and empagliflozin. Common dipeptidyl peptidase-4 (DPP-4) inhibitors, used as the comparator, include alogliptin, linagliptin, saxagliptin, sitagliptin, or vildagliptin.

We don’t Rx it, but we deal with the fallout.
This large Canadian database (~3M patients) found the risk of DKA in type 2 diabetes patients taking SGLT-2 inhibitors compared with DPP-4 inhibitors was nearly three times greater; incidence rates 2.03 vs 0.75/1000 person-years; HR 2.85 (95%CI 1.99-4.08). They used propensity score matching and time of exposure to each drug to develop the cohorts, each with 208,757 patients. As emergency physicians, we need to be aware of this adverse drug effect. If you see a patient with type 2 diabetes, anion gap acidosis, and normal to slightly elevated glucose, take a look at the medication list and consider that this still may be a case of DKA if you see a SGLT-2 inhibitor on the med list. In reverse, take a look at the medication list, and if you see a SGLT-2 inhibitor and the patient looks unwell, check labs to look for DKA.

Sodium-Glucose Cotransporter-2 Inhibitors and the Risk for Diabetic Ketoacidosis : A Multicenter Cohort Study. Ann Intern Med. 2020 Sep 15;173(6):417-425. doi: 10.7326/M20-0289. Epub 2020 Jul 28.

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3 thoughts on “Can You Spot Euglycemic DKA From SGLT-2 Inhibitors?”


    Perhaps for these tricky cases, especially with a neither-here-nor-there gas, beta-hydroxybutyrate levels will be optimal to cinch the diagnosis

    Sadly don’t have this in my shop within a good time frame

    A Roux
    Emerg Doc
    South Africa


      Seems like you could develop a high suspicion if you saw one of these drugs, symptoms of DKA, anion gap acidosis, and ketonuria even if you can’t get a rapid beta-hydroxybutyrate.

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