Case Report: Tirzepatide and SGLT-2 Inhibitors Linked to Euglycemic DKA on Sick Days

Both tirzepatide (a dual GIP/GLP-1 receptor agonist) and sodium-glucose cotransporter 2 (SGLT-2) inhibitors are powerful medications for managing Type 2 Diabetes, known for their significant blood-glucose-lowering and body-weight-reducing effects. However, the incidence of euglycemic diabetic ketoacidosis (EDKA), a serious condition where the body produces high levels of ketones despite normal blood sugar, has been on the rise, particularly with increased SGLT-2 inhibitor use and associated appetite loss. This study addresses the critical need to understand the risks of continuing these medications during acute illness or 'sick-day conditions'.

The patient experienced euglycemic diabetic ketoacidosis (EDKA) as a direct consequence of continuing tirzepatide and SGLT-2 inhibitors during an acute illness. This aligns with previous observations that 14% of patients treated with tirzepatide experience appetite loss, a known risk factor for EDKA when combined with SGLT-2 inhibitors. The critical finding was that after the patient recovered from the sick-day condition and EDKA, both tirzepatide and the SGLT-2 inhibitor were successfully reintroduced without any further adverse effects. This suggests that the adverse event was specifically tied to the sick-day continuation protocol rather than an inherent intolerance to the drugs themselves. The most important finding is that temporary discontinuation of tirzepatide and SGLT-2 inhibitors during sick-day conditions is crucial to prevent EDKA, but reintroduction post-recovery appears safe.