Sodium-glucose cotransporter-2 inhibitors for hypergycemia in phosphoinositide 3-kinase pathway inhibition Journal Article
| Authors: | Weintraub, M. A.; Liu, D.; DeMatteo, R.; Goncalves, M. D.; Flory, J. H. |
| Article Title: | 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. © 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. |
| Keywords: | adult; controlled study; treatment outcome; major clinical study; drug efficacy; drug safety; follow up; enzyme inhibition; incidence; cohort analysis; breast neoplasms; medical record review; retrospective study; phosphatidylinositol 3 kinase; hyperglycemia; breast tumor; glucose blood level; antidiabetic agent; blood glucose; metastatic breast cancer; sodium; metformin; drug exposure; adverse effects; phosphatidylinositol 3-kinase; phosphatidylinositol 3-kinases; diabetic ketoacidosis; pik3ca; point of care testing; hypoglycemic agents; humans; human; male; female; article; alpelisib; meglitinide; dipeptidyl peptidase iv inhibitor; sodium glucose cotransporter 2 inhibitor; sodium-glucose transporter 2 inhibitors |
| Journal Title: | Breast Cancer Research and Treatment |
| Volume: | 203 |
| Issue: | 1 |
| ISSN: | 0167-6806 |
| Publisher: | Springer |
| Date Published: | 2024-01-01 |
| Start Page: | 85 |
| End Page: | 93 |
| Language: | English |
| DOI: | 10.1007/s10549-023-07110-y |
| PUBMED: | 37704834 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in PubMed and PDF -- Corresponding author is MSK author: James H. Flory -- Source: Scopus |
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