Study Shows Association Between Alpelisib Treatment, Hyperglycemia in Patients with Metastatic Breast Cancer


The study authors suggest that after initiating alpelisib, patients should be proactive by improving glycemic status to reduce the risk of developing hyperglycemia.

New research indicates that patients with metastatic breast cancer who were treated with the oral medication alpelisib had elevated rates of high blood sugar—or hyperglycemia. Alpelisib targets the phosphoinositide 3-kinase (PI3K) protein that is involved in cell growth that when mutated, can contribute to cancer.1

Woman holding a glass of water and a pill

Image credit: New Africa |

The FDA approved the use of this alpelisib with fulverstrant—an estrogen receptor blocker—in 2019. The combination therapy is used to treat certain cases of metastatic breast cancer that have mutations in the gene that codes for a PI3K subunit; however, targeting PI3K can result in hyperglycemia, which can cause dehydration or kidney damage that leads to hospitalization if severe.1

“If a patient is identified to have a PI3KCA mutation and thus eligible for treatment with alpelisib, we should be checking hemoglobin A1c (HbA1c) level and partnering with the patient’s primary care physician and/or endocrinologist to optimize their blood sugar levels,” said lead author Sherry Shen, MD, Memorial Sloan Kettering Cancer Center, in a press release.1

The findings come from a clinical study published in Cancer that evaluated the incidence, risk factors, and treatment of alpelisib-associated hyperglycemia in patients with metastatic breast cancer treated with alpelisib. The study found that rates of hyperglycemia among those treated with alpelisib as standard care were significantly higher than patients treated during clinical trials. In the trial, 152 (61.5%) out of a total 247 patients had developed any-grade hyperglycemia, and 72 patients (29.2%) had developed grade 3 to 4 hyperglycemia at a median time onset of 16 days.2

“[Optimizing patients’ HbA1c levels] needs to be done months before initiating alpelisib, because once [it] is started, hyperglycemia usually develops within the first 2 weeks of treatment. Being pre-emptive about improving glycemic status and treating prediabetes or diabetes will hopefully lower the patient’s risk of developing hyperglycemia and thus, lower their risk of needing to discontinue a drug that could be effective for their cancer,” Shen said in the press release.1

A total of 100 patients (40.5%) had received aplelisib on a clinical trial, with rates of hyperglycemia being significantly higher in patients treated as standard care versus during a clinical trial (any-grade hyperglycemia 80.3% vs. 34.0%, grade 3–4 hyperglycemia 40.2% vs. 13.0%, p < .001). Further, baseline HbA1c was highly associated with the development of hyperglycemia as well as apelisib dose reduction or discontinuation. Of those who developed hyperglycemia, 101 patients (40.9%) received treatment—most commonly with metformin, a diabetes drug—and 49 (19.8%) patients were referred to an endocrinologist for treatment.1,2

“Improving metabolic risk factors through lifestyle interventions may also improve dose delivery of alpelisib, and ongoing clinical trials by our group and other groups are testing whether metabolic interventions such as the ketogenic diet or newer medications used to treat diabetes could also improve the treatment efficacy of cancer therapies that target the PI3K pathway,” senior author Neil Iyengar, MD, noted in the press release.1


1. Wiley. New insights on a potentially serious side effect of the cancer drug alpelisib. News release. September 25, 2023. Accessed September 28, 2023.

2. Shen, S, Chen, Y, Carpio, A, Chang, C, Iyengar, NM. Incidence, risk factors, and management of alpelisib-associated hyperglycemia in metastatic breast cancer. Cancer. 2023; 1-8. doi:10.1002/cncr.34928

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