<b>Ketosis and ketoacidosis reported with tirzepatide and semaglutide in JADER: overall</b><b> </b><b>and</b><b> </b><b>non-approved</b><b> </b><b>or inappropriate use</b>

Incretin-based therapies provide benefits for type 2 diabetes and obesity, and their use is rapidly expanding. However, non-approved or inappropriate use is also increasing, sometimes without adequate medical supervision, raising safety concerns. Among these concerns, ketosis and ketoacidosis have recently attracted attention, but their real-world reporting patterns remain unclear.</p><p dir="ltr">

Methods

To characterize real-world reporting patterns of ketosis and ketoacidosis with tirzepatide and semaglutide, we analyzed the July 2026 release of the Japanese Adverse Drug Event Report (JADER) database, maintained by the Pharmaceuticals and Medical Devices Agency (PMDA). Reports listing either drug as a suspected drug were assessed overall and for non-approved or inappropriate use based on recorded indications and dosing information.

Demographic characteristics and selected adverse-event categories were summarized descriptively.</p><p dir="ltr">Results: Ketone-related events were recorded in 75 of 890 tirzepatide reports (8.4%) and 69 of 730 semaglutide reports (9.5%) overall. The non-approved/inappropriate-use groups comprised 61 tirzepatide and 20 semaglutide reports; all involved Mounjaro and Ozempic/Rybelsus, respectively. Females accounted for 75.4% and 75.0% of these reports, and individuals aged 10–29 years for 44.3% and 50.0%.

Ketone-related events were recorded in 12 tirzepatide reports (19.7%) and no semaglutide report. All 12 involved weight-loss or cosmetic use, and 11 involved females aged 10–29 years.</p><p dir="ltr">Conclusions: These findings suggest a distinct reporting pattern of ketone-related events in the context of non-approved or inappropriate use, particularly weight-loss or cosmetic use of tirzepatide. This pattern warrants clinical awareness, while its incidence and underlying mechanisms require investigation in studies with exposure denominators and detailed clinical data.</p><p dir="ltr">Funding: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.</p>