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

Abstract

PURPOSE:

Phosphoinositide 3-kinase (PI3K) inhibition is used for the treatment of certain cancers, but can cause profound hyperglycemia and insulin resistance, for which sodium-glucose cotransporter-2 (SGLT2) inhibitors have been proposed as a preferred therapy. The objective of this research is to assess the effectiveness and safety of SGLT2 inhibitors for hyperglycemia in PI3K inhibition.

METHODS:

We conducted a single-center retrospective review of adults initiating the PI3K inhibitor alpelisib. Exposure to different antidiabetic drugs and adverse events including diabetic ketoacidosis (DKA) were assessed through chart review. Plasma and point-of-care blood glucoses were extracted from the electronic medical record. Change in serum glucose and the rate of DKA on SGLT2 inhibitor versus other antidiabetic drugs were examined as co-primary outcomes.

RESULTS:

We identified 103 patients meeting eligibility criteria with median follow-up of 92 days after starting alpelisib. When SGLT2 inhibitors were used to treat hyperglycemia, they were associated with a decrease in mean random glucose by -46 mg/dL (95% CI - 77 to - 15) in adjusted linear modeling. Five cases of DKA were identified, two occurring in patients on alpelisib plus SGLT2 inhibitor. Estimated incidence of DKA was: alpelisib plus SGLT2 inhibitor, 48 DKA cases per 100 patient-years (95% CI 6, 171); alpelisib with non-SGLT2 inhibitor antidiabetic drugs, 15 (95% CI 2, 53); alpelisib only, 4 (95% CI 0.1, 22).

CONCLUSIONS:

SGLT2 inhibitors are effective treatments for hyperglycemia in the setting of PI3K inhibition.

• Authors: Michael A Weintraub, Dazhi Liu, Raymond DeMatteo, Marcus DaSilva Goncalves, James H Flory
• Journal: Breast cancer research and treatment (Breast Cancer Res Treat) (Sep 13 2023) ISSN: 1573-7217 [Electronic] Netherlands
• PMID: 37704834 (Publication Type: Journal Article)
• Copyright: © 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.