Drug-Induced Hyperglycemia More Common in Clinical Practice


New research suggests that 80% of women who receive the PI3K inhibitor alpelisib (Piqray, Vijoice) as standard treatment for metastatic breast cancer develop hyperglycemia, a rate far higher than the 34% rate seen in clinical trials.


  • Fulvestrant (Faslodex) plus alpelisib improves progression-free survival (PFS) in metastatic hormone receptor-positive, PIK3CA-mutant breast cancer.

  • Hyperglycemia is a known side effect of PI3K inhibitor therapy but data on its incidence and management in everyday clinical practice remain sparse.

  • To investigate, researchers reviewed data on 247 patients (mean age 62) with metastatic breast cancer who received alpelisib between 2013 and 2021.

  • The researchers compared hyperglycemia rates between the 147 patients treated with alpelisib in routine clinical practice and the 100 patients who received the drug as part of a clinical trial. Baseline median BMI was 25.4 kg/m2 and median A1c was 5.5%.


  • Among all 247 patients, 152 (62%) developed any-grade hyperglycemia and 72 (29%) developed grade 3-4 hyperglycemia. The median time to onset was 16 days.

  • Rates of hyperglycemia were significantly higher in patients treated in clinical practice vs on a clinical trial (any grade, 80% vs 34%; grade 3-4, 40% vs 13%; P < .001).

  • Elevated BMI correlated with elevated A1c, and baseline A1c in the prediabetes or diabetes range was significantly associated with developing hyperglycemia (P < .001) as well as with alpelisib dose reduction or discontinuation (P = .015).

  • Dose reduction/discontinuation due to hyperglycemia occurred in 29% in the standard care cohort vs 10% in the clinical trial cohort; 41% of patients who developed hyperglycemia received treatment, most commonly with metformin; 20% were referred to an endocrinologist.


“These observations indicate that the frequency of alpelisib-associated hyperglycemia is substantially greater in standard clinical practice than in clinical trials, and the identification of glycemic status as a modifiable risk factor offers the potential to mitigate this adverse effect and improve treatment delivery,” the authors say. “Reassuringly,” they added, “there was no significant difference in PFS between patients who developed hyperglycemia and those who did not.”


The study, led by first author Sherry Shen, MD, Memorial Sloan Kettering Cancer Center, New York City, was published online September 25 in the journal Cancer.


Serum glucose levels were abstracted from electronic health records that did not differentiate fasting and nonfasting status. The cohort was mostly White women from a single institution.


This work was supported in part through a National Institutes of Health/National Cancer Institute (NIH/NCI) Cancer Center support grant. Shen reported receiving honoraria from MJH Life Sciences. Senior author Neil M. Iyengar, MD, receives consultant fees from Novartis, Pfizer, Seattle Genetics, and TerSera Therapeutics, and research funding (to institution) from Novartis and SynDevRx.

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