Severe Life-Threatening Ketoacidosis After Combining Tirzepatide With an SGLT2 Inhibitor in a Type 1 Diabetes Patient

This is a single-patient case report from a large tertiary care center in Karachi, Pakistan, with a brief review of relevant literature. The clinical course, laboratory findings, treatment, and outcome were documented prospectively during the patient's hospital admission.

Tirzepatide (Mounjaro/Zepbound) is one of the most popular new medications for diabetes and weight loss, while SGLT2 inhibitors like empagliflozin are widely used for diabetes and heart failure. This case demonstrates that combining these drug classes in type 1 diabetes patients can trigger life-threatening ketoacidosis that may be missed because blood sugar levels remain deceptively normal — a critical safety consideration as off-label use of these medications expands.

As GLP-1/GIP agonists like tirzepatide are increasingly prescribed — sometimes off-label in type 1 diabetes patients — understanding their interactions with other diabetes medications is critical. Euglycemic DKA is particularly dangerous because its normal-appearing blood sugar readings can delay diagnosis. This case adds to growing evidence that the combination of incretin-based therapies and SGLT2 inhibitors in type 1 diabetes requires extreme caution and patient education about ketoacidosis symptoms.

This is a single case report, which represents the lowest level of clinical evidence. It cannot establish a definitive causal relationship between the drug combination and the euDKA event. Individual patient factors may have contributed. The elevated amylase suggesting pancreatic involvement is speculative. The findings may not be generalizable to all patients combining these medications.