Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical EndocrinologistsJun 5, 2026

Analysis of Increased Risk of Ketoacidosis Linked to Tirzepatide

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗

Updated Jun 6, 2026

Abstract

Starvation ketoacidosis generated the strongest signal with a PRR of 70.2.

Ketosis NOS and euglycemic DKA showed moderate signals with PRRs of 4.27 and 2.01, respectively.
The findings suggest that tirzepatide may be associated with multiple ketoacidosis-spectrum events.
The strong signal for starvation ketoacidosis may be linked to appetite suppression and caloric restriction caused by tirzepatide.
Euglycemic DKA signals could be particularly relevant in situations involving peri-operative care or dietary restrictions.
Limitations in the FAERS data restrict the ability to determine causal relationships.

Simplified

BACKGROUND: Tirzepatide, a dual GIP/GLP-1 receptor agonist approved for type 2 diabetes and obesity, has generated post-marketing reports of ketoacidosis-spectrum events. Systematic pharmacovigilance characterization is lacking.

METHODS: All tirzepatide reports were extracted from the FDA Adverse Event Reporting System (FAERS) through March 2026. Disproportionality was assessed using the Proportional Reporting Ratio (PRR; signal threshold: PRR ≥ 2, χ≥ 4, n ≥ 3) and Reporting Odds Ratio (ROR) across four MedDRA preferred terms: ketoacidosis NOS, euglycemic DKA, starvation ketoacidosis, and ketosis NOS. 2

RESULTS: Starvation ketoacidosis generated the strongest signal (PRR 70.2, χ1560.7; ROR 70.3 [95% CI 46.9-105.2]). Ketosis NOS and euglycemic DKA produced moderate but statistically robust signals meeting all frequentist thresholds (PRR 4.27 and 2.01, respectively). 2

CONCLUSIONS: The starvation ketoacidosis signal is biologically plausible given tirzepatide-mediated appetite suppression and caloric restriction. Euglycemic DKA signals are clinically relevant in peri-operative or dietary restriction contexts. FAERS limitations preclude causal inference. Physicians may consider counseling patients about ketoacidosis symptoms and maintain a low threshold for ketone testing in symptomatic individuals on tirzepatide.

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Analysis of Increased Risk of Ketoacidosis Linked to Tirzepatide

Abstract

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