Euglycemic diabetic ketoacidosis following treatment with tirzepatide and SGLT-2 inhibitors: A case report and literature review.

Internal medicine (Tokyo, Japan)2026PMID: 41850834

View on PubMed DOI: 10.2169/internalmedicine.6816-25

Plain Language Summary

Case report and literature review of euglycemic diabetic ketoacidosis (EDKA) occurring after continuation of tirzepatide combined with an SGLT2 inhibitor during a sick-day illness, highlighting the additive risk when both agents that promote ketogenesis are continued during reduced oral intake. Reviews the mechanism of EDKA in this drug combination context. Provides a clinically critical safety warning for the common tirzepatide plus SGLT2 inhibitor combination—establishing that sick-day rules must include temporary discontinuation of both agents to prevent the increasingly recognized EDKA complication.

Abstract

Tirzepatide is a novel antidiabetic agent with strong blood-glucose-lowering and body-weight-reducing effects. However, 14% of the patients treated with tirzepatide experienced appetite loss. The incidence of euglycemic diabetic ketoacidosis (EDKA) has recently increased with the heightened use of sodium-glucose cotransporter 2 (SGLT-2) inhibitors and the consequent appetite loss. Therefore, the temporary discontinuation of tirzepatide and SGLT-2 inhibitors is required under sick-day conditions. We herein report a case of EDKA that developed after the continuation of tirzepatide and SGLT-2 inhibitor on sick-day condition. After recovery from the sick-day condition, both agents were successfully reintroduced without any adverse effects.

Authors

Sawamura, Toshitaka; Karashima, Shigehiro; Ohmori, Ai; Nishimoto, Yuya; Kometani, Mitsuhiro; Yoneda, Takashi

Keywords

SGLT-2 inhibitorSick-dayeuglycemic diabetic ketoacidosistirzepatide