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Sodium-glucose cotransporter-2 inhibitors for hypergycemia in phosphoinositide 3-kinase pathway inhibition

Michael A Weintraub1, Dazhi Liu2, Raymond DeMatteo2

  • 1New York University Diabetes & Endocrine Associates, 222 East 41st Street, 23rd Floor, New York, NY, 10017, USA.

Breast Cancer Research and Treatment
|September 13, 2023
PubMed
Abstract

Insights

Sodium-glucose cotransporter-2 (SGLT2) inhibitors effectively manage hyperglycemia caused by phosphoinositide 3-kinase (PI3K) inhibitors. While generally safe, careful monitoring for diabetic ketoacidosis (DKA) is recommended when used concurrently.

Area of Science:

  • Endocrinology and Oncology
  • Pharmacology and Therapeutics

Background:

  • Phosphoinositide 3-kinase (PI3K) inhibitors are utilized in cancer treatment.
  • PI3K inhibition can induce significant hyperglycemia and insulin resistance.
  • Sodium-glucose cotransporter-2 (SGLT2) inhibitors are a potential therapeutic option for managing this hyperglycemia.

Purpose of the Study:

  • To evaluate the efficacy of SGLT2 inhibitors in treating hyperglycemia associated with PI3K inhibitor therapy.
  • To assess the safety profile of SGLT2 inhibitors in this patient population, with a focus on diabetic ketoacidosis (DKA).

Main Methods:

  • Retrospective review of adult patients initiating the PI3K inhibitor alpelisib.
  • Analysis of antidiabetic drug exposure, including SGLT2 inhibitors.
  • Assessment of adverse events, particularly DKA, and changes in serum glucose levels.

Main Results:

  • SGLT2 inhibitor use was associated with a mean reduction in random glucose of -46 mg/dL.
  • Five cases of DKA were observed; two occurred in patients receiving alpelisib plus SGLT2 inhibitors.
  • The estimated incidence of DKA was higher with alpelisib plus SGLT2 inhibitors (48/100 patient-years) compared to other regimens.

Conclusions:

  • SGLT2 inhibitors demonstrate effectiveness in managing hyperglycemia in patients treated with PI3K inhibitors.
  • The concurrent use of SGLT2 inhibitors with PI3K inhibitors warrants careful monitoring due to an increased risk of DKA.
Keywords:
Adverse effectsAlpelisibHyperglycemiaMetastatic breast cancerPIK3CA

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