SAT-635 - A Retrospective Study on the Factors Contributing to Diabetic Ketoacidosis and Euglycemic Diabetic Ketoacidosis in the Setting of SGLT2 Inhibitors

Introduction
The prevalence of euglycemic diabetic ketoacidosis (EDKA), defined as a glucose < 250mg/dL, has increased with widespread use of SGLT2 inhibitors. Approximately 2.6% to 3.2% of DKA admissions are euglycemic. EDKA associated with the use of SGLT2 inhibitors has rates ranging from 0.16 to 0.76 events per 1000 patients. Further, it is estimated that SGLT2 inhibitors increase the risk of DKA in patients with type 2 diabetes mellitus (DM2) by 7-fold. Given this trend, we sought to explore further risk factors that can exacerbate or contribute to the presentation of both DKA and EDKA in the setting of SGLT2 use.

There have been limited studies exploring the risk factors between development of DKA in patients taking SGLT2 inhibitors. One study looking at case reports, found that common risk factors were patients with the diagnosis of DM2 who were later identified as having latent autoimmune diabetes of adulthood, recent major surgery, and decreasing or discontinuing insulin. Another systemic review found that females with DM2, recent surgery, and metformin use were associated with EDKA in patients receiving SGLT2 inhibitors.

Methods
We conducted a retrospective study of non-pregnant patients age 21 or older who presented with DKA while taking an SGLT2 inhibitor at our institution between January 1, 2018 to April 11, 2025.

Results
There were 520 admissions for DKA within the study time period, of which only 32 patients were taking SGLT2 inhibitors at the time of admission. Fourteen of the 32 patients presented with EDKA (43.8%). Twelve out of the 32 patients (37.5%) were female, and 20 patients (62.5%) were male. Forty-point six percent were White, 21.9% were Hispanic, 18.8% were Black/African American, 9.4% were Asian, and 9.4% were other/unknown.

The most common precipitating factor for DKA was medication non-compliance (31.3%), followed by SGLT2 initiation (18.7%), and acute infection (15.6%). Thirteen out of 32 patients (40.6%) were prescribed insulin at the time of admission. Only 2 patients had a well-controlled A1c of ≤7%, while 20 patients (62.5%) had an A1c of ≥10%.

DKA was diagnosed within 1 week of initiation of SGLT2 inhibitor in 5 patients, of which 3 had EDKA. These patients had no additional precipitating factors for DKA. Only 1 was prescribed insulin at baseline but was non-compliant. All 5 patients had uncontrolled DM2 at baseline with A1c ranging from 11.1 – 13.2% at the time of admission.

Conclusion
Our observations indicate that DKA and EDKA were more associated with uncontrolled DM (A1c ≥10%) and non-compliance with diabetic medications in patients taking SGLT2 inhibitors. Due to its small sample size, the logistic regression analysis was not expected to be significant. Despite these findings, our observations do suggest that caution should be taken in starting SGLT2 inhibitors in patients with poorly controlled DM who are not currently on insulin therapy.

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