Alpelisib for long-term management of tumor-induced hypoglycemia Journal Article
| Authors: | Ryan, T. J.; Raj, N.; Reidy, D.; Goncalves, M. D.; Flory, J. H. |
| Article Title: | Alpelisib for long-term management of tumor-induced hypoglycemia |
| Abstract: | Background/Objective: Tumor-induced hypoglycemia (TIH) is a rare and often fatal complication of cancers that produce or induce secretion of hormones such as insulin, insulin-like growth factor 2, and proinsulin. We present a case series describing the effectiveness and tolerability of the phosphatidylinositol 3-kinase inhibitor alpelisib in 2 women with metastatic insulin-producing or proinsulin-producing tumors. Case Presentation: Over 4 to 8 months of follow-up, it was observed that alpelisib resulted in reductions in hypoglycemic rates (<54 mg/dL) as assessed on continuous glucose monitoring. For the first patient, the proportion of glucose readings <54 mg/dL fell from 2.3% (95% CI, 2.1-2.4) to 0.2% (95% CI, 0.2%-0.3%), and the rate ratio was 0.087 (95% CI, 0.086-0.089). For the second patient, the proportion of low glucose readings fell from 9.0% (95% CI, 8.6-9.4) to 2.0% (95% CI, 2.2%-2.5%), and the rate ratio was 0.26 (95% CI, 0.26-0.27). Alpelisib was not associated with significant adverse events. There was one instance of gastrointestinal bleeding that was likely not attributable to alpelisib. Due to high cost and off-label use, the process of obtaining alpelisib was complex and took several months for the first patient and 2 years for the second patient. Discussion: Treatment options for TIH are limited. Alpelisib, a small-molecule phosphatidylinositol 3-kinase inhibitor, may blunt the hypoglycemic effect of excess insulin and proinsulin by decreasing glucose transport and increasing glycogenolysis and gluconeogenesis. Conclusion: Alpelisib appears to be effective and well tolerated for long-term treatment of TIH. (c) 2025 American Association of Clinical Endocrinologists. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
| Keywords: | insulin; hypoglycemia; insulinoma; diazoxide; proinsulin; alpelisib; tumor-induced hypoglycemia |
| Journal Title: | Aace Endocrinology and Diabetes |
| Volume: | 12 |
| Issue: | 1 |
| ISSN: | 3050-9157 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2025-05-01 |
| Language: | English |
| ACCESSION: | WOS:001525689800002 |
| DOI: | 10.1016/j.aed.2025.03.010 |
| PROVIDER: | wos |
| PMCID: | PMC12268652 |
| PUBMED: | 40677791 |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledge in the PDF -- Corresponding authors is MSK author: James H. Flory -- Source: Wos |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work