Insulin-Recalcitrant Hyperglycemia Following Capivasertib Therapy: A Novel Challenge in a Non-Diabetic Patient
https://doi.org/10.15605/jafes.041.S1
- Author:
Jun Yang Tan
1
;
Waye Hann Kang
1
Author Information
1. Department of Medicine, M. Kandiah Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman
- Publication Type:Journal Article
- MeSH:
capivasertib;
Hyperglycemia;
Insulins
- From:
Journal of the ASEAN Federation of Endocrine Societies
2026;41(S1):51-
- CountryPhilippines
- Language:English
-
Abstract:
Introduction:Capivasertib is a selective oral AKT inhibitor approved
for hormone receptor-positive, HER2-negative advanced
breast cancer with AKT pathway mutations. As AKT is
integral to insulin signaling, its inhibition predisposes
patients to hyperglycemia. We report a case of severe
capivasertib-induced hyperglycemia with profound insulin
resistance in a non-diabetic patient.
Case:A 56-year-old female with metastatic breast cancer (ER/
PR-positive, HER2-negative, AKT1- and ESR1-mutated,
TMB-high) presented with severe hyperglycemia following
capivasertib initiation. She had no prior diabetes history,
with a baseline hemoglobin A1c of 5.6%. Her first cycle
(200 mg twice daily, 7 April 2025) was uncomplicated
metabolically. The second cycle was escalated to 400 mg
twice daily on 21 April 2025. By Day 3, blood glucose rose
significantly. Premixed insulin 20 units failed to achieve
glycemic control, necessitating intravenous insulin infusion.
Despite escalation to 30 units per hour, euglycemia could not
be achieved. Notably, there was no biochemical evidence
of diabetic ketoacidosis or hyperosmolar hyperglycemic
state, and the patient remained hemodynamically stable.
No corticosteroids or other contributing medications were
administered. Blood glucose normalized spontaneously
approximately 36 hours after the last capivasertib dose, and
all insulin was weaned and discontinued by 26 April 2025.
She remained euglycemic without antidiabetic therapy
thereafter. The patient and family opted for palliative care,
and she passed away on 6 May 2025.
Conclusion:Capivasertib can precipitate severe, insulin-resistant
hyperglycemia even in non-diabetic patients, without
progression to overt hyperglycemic crisis. Spontaneous
resolution upon drug cessation supports a direct drugmediated mechanism via AKT-disrupted insulin signaling.
Clinicians should monitor glucose closely during
therapy and consider drug cessation in refractory cases.
Further studies are warranted to guide optimal glycemic
management.
- Full text:2026073014032662235EP_A058.pdf
