Alpelisib-Induced Diabetic Ketoacidosis: A Case Report and Review of Literature

Abstract

Objective: To report the first case of diabetic ketoacidosis (DKA) and its management in a patient with diet-controlled prediabetes and metastatic breast cancer treated with alpelisib, a PI3K (phosphatidylinosiotol-3-kinase) inhibitor.

Methods: Literature on the topic is reviewed. The case is that of a 66-year-old female with diet-controlled prediabetes and metastatic breast carcinoma who had initiated alpelisib 2 weeks prior to being admitted for diabetic ketoacidosis.

Results: Admission laboratory examination revealed a blood sugar of 1137 mg/dL, an anion gap of 25, large ketones in urine, and positive acetone in serum. The HbA1c level was 9.4% (79 mmol/mol) on admission, which had been 6.3% (45 mmol/mol) seven months earlier. She was discharged on subcutaneous insulin and instructed to discontinue alpelisib. Alpelisib was restarted 2 days later, which exacerbated her hyperglycemia within 24 hours. In the following months, her hyperglycemia was successfully managed with insulin and a SGLT 2 inhibitor. Unfortunately, her breast cancer progressed, ultimately leading to discontinuation of alpelisib. Blood sugar levels returned to a nondiabetic range upon discontinuation of alpelisib, and she is currently off all antihyperglycemic agents.

Conclusion: Although PI3KCA inhibitors remain a promising drug in patients with metastatic breast cancer who have not responded to previous treatment, patients must be closely monitored for adverse effects such as hyperglycemia. Hyperglycemia could be a potentially limiting side effect of alpelisib. The optimal management of hyperglycemia induced by alpelisib warrants further research.

Keywords: Akt, protein kinase B; DKA; DKA, diabetic ketoacidosis; HbA1c, glycosylated hemoglobin; PI3K, phosphatidylinosiotol-3-kinase; SGLT2, sodium glucose cotransporter 2; alpelisib; oncology; type 2 diabetes.

Fig 1

Continuous glucose monitor tracing for 3 consecutive days while the patient was on lispro 30 units prior to breakfast (at 07:00 hours), 18 units prior to lunch (at 12:00 hours), and 17 units prior to dinner (at 16:00 hours) along with A, alpelisib 300 mg and 25 mg empagliflozin at 19:30 hours and degludec 60 units taken at 23:00 hours; B, alpelisib 300 mg and 25 mg empagliflozin 23:00 hours and degludec 60 units taken at 23:00 hours; and C, alpelisib 300 mg and 25 mg empagliflozin at 19:00 hours and degludec 60 units taken at 22:00 hours.

Fig 2

Continuous glucose monitor tracing for 3 consecutive days while the patient was on lispro 32 units prior to breakfast (07:00 hours ), 18 units prior to lunch (12:00 hours ), and 18 units prior to dinner (16:00 hours) along with A, alpelisib 300 mg and 25 mg empagliflozin at 19:30 hours and detemir 60 units taken at 23:00 hours ; B, alpelisib 300 mg and 25 mg empagliflozin at 19:00 hours and detemir 60 units taken at 22:00 hours; C, alpelisib 300 mg and 25 mg empagliflozin at 19:15 hours and detemir 60 units taken at 22:00 hours.

Fig 3

Continuous glucose monitor tracing for 3 consecutive days after the patient had discontinued alpelisib, empagliflozin, and insulin therapy.