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

The takeaway

A 41-year-old woman with type 1 diabetes developed severe euglycemic diabetic ketoacidosis (pH 6.96) requiring intubation after starting tirzepatide for weight loss while already taking empagliflozin and insulin.

Blood pH 6.96
The patient's blood became critically acidic (normal pH is 7.35-7.45), yet her blood sugar was only mildly elevated at 190-200 mg/dL — illustrating how euglycemic DKA can be life-threatening while appearing deceptively mild on glucose readings alone.

What the researchers found

A 41-year-old female with type 1 diabetes developed severe euglycemic diabetic ketoacidosis (euDKA) after initiating tirzepatide for weight loss while already taking empagliflozin and basal-bolus insulin therapy. Key clinical findings:

- Blood pH: 6.96 (critically low; normal is 7.35-7.45)

- Bicarbonate: 1.5 mmol/L (critically low; normal is 22-28 mmol/L)

- Blood glucose: only 190-200 mg/dL (mildly elevated, masking the severity)

- Amylase: 688 U/L (elevated, suggesting possible pancreatic stress from tirzepatide)

- No infection or other precipitating cause was identified

The severity required intubation and intravenous bicarbonate therapy. The patient recovered after intensive insulin and fluid replacement.

Why it matters

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.

How the study worked

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.

What this study cannot tell us

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.

How to read the evidence

This is a single case report, which provides the lowest level of clinical evidence. While it documents an important adverse event and raises a safety signal, a single case cannot establish the frequency or definitive causation of the complication. It serves primarily as a clinical alert for practitioners.

When this study was published

Published in 2026, this is a very recent case report that is directly relevant to current prescribing patterns, as tirzepatide use continues to expand rapidly worldwide.

The bigger picture

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.

Questions still open

How common is euglycemic DKA when tirzepatide is combined with SGLT2 inhibitors in type 1 diabetes patients?
Should there be formal contraindication warnings against using tirzepatide and SGLT2 inhibitors together in type 1 diabetes?
What monitoring protocols could help detect euglycemic DKA early in patients on these combination therapies?

Common questions

What is euglycemic diabetic ketoacidosis and why is it dangerous?

Euglycemic DKA is a form of diabetic ketoacidosis where the blood becomes dangerously acidic from a buildup of ketones, but blood sugar levels remain normal or only slightly elevated. It's particularly dangerous because doctors and patients typically associate DKA with very high blood sugar — so when glucose looks normal (190-200 mg/dL in this case), the life-threatening acidosis can be missed or diagnosed late.

Is it safe to take tirzepatide (Mounjaro) with an SGLT2 inhibitor?

This case report raises a safety concern about combining tirzepatide with SGLT2 inhibitors, particularly in type 1 diabetes patients. The combination appeared to trigger severe ketoacidosis despite near-normal blood sugar. While this is a single case and doesn't prove the combination is always dangerous, it suggests clinicians should exercise caution and patients should be educated about ketoacidosis warning signs (nausea, vomiting, rapid breathing) regardless of glucose readings.

Read the original research

Severe Euglycemic Diabetic Ketoacidosis Requiring Intubation After Tirzepatide and SGLT2 Inhibitor Coadministration in a Patient With Type 1 Diabetes Mellitus From a Large Tertiary Care Centre in Karachi, Pakistan: A Case Report and Brief Review of the Literature.

Clinical case reports, 14(2), e71929

View on PubMed ↗Publisher’s paper ↗

Citation

Malik, Maliha; Amjad, Hammad; Malik, Khadija; Saleem, Muddassir Syed; Akhtar, Shanzay; Paracha, Muslehuddin; Abid, Mobeen; Shafi, Nabahat; Raza, Ahmed Asad; Samadi, Abedin; Jaffri, Samar Abbas. (2026). Severe Euglycemic Diabetic Ketoacidosis Requiring Intubation After Tirzepatide and SGLT2 Inhibitor Coadministration in a Patient With Type 1 Diabetes Mellitus From a Large Tertiary Care Centre in Karachi, Pakistan: A Case Report and Brief Review of the Literature.. Clinical case reports, 14(2), e71929. https://doi.org/10.1002/ccr3.71929