Novel breast cancer treatment leads to hyperglycaemia

Abstract

A 66-year-old woman with pre-diabetes and hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer was started on fulvestrant, and referred to endocrinology prior to initiation of alpelisib. Because of anticipated possible hyperglycaemia, and the woman's reluctance to start fingerstick glucose monitoring, a continuous glucose monitor (CGM) was prescribed for safety. CGM data revealed the rapid onset of hyperglycaemia over the first 2 weeks of alpelisib treatment with nocturnal hyperglycaemia (Fig. 1). Hyperglycaemia occurred in the first 6 h after each dose was administered, and after 2 weeks average daily glucose levels were three times higher than baseline.Questions 1. What is alpelisib? Why does alpelisib cause hyperglycaemia?3. How is alpelisib-induced hyperglycaemia treated? FIGURE 1 Two-week continuous glucose monitoring data from woman with breast cancer the day after initiating alpelisib. The woman took alpelisib daily at 6pm. Daily average (Avg) glucose readings are shown.ª 2020 Diabetes UK

Alpelisib-Induced Diabetes Mellitus: Case Report, Pharmacodynamics and Management Considerations

“…Despite the lack of detailed information available on the pharmacokinetics of alpelisib, FGM has been helpful in understanding the pharmacodynamic aspects of alpelisib and provides valuable information that correlates with its pharmacokinetic properties. There are barely any studies describing in sufficient detail the day-to-day pattern related to alpelisib administration, the rapid onset alpelisib-induced hyperglycemia and its prompt reversibility (10). In this regard, the information provided by the FGM has been extremely helpful in understanding the pharmacodynamic aspects of alpelisib and has also provided valuable information that correlates with its pharmacokinetic properties.…”

Immune checkpoint inhibitor– and phosphatidylinositol-3-kinase inhibitor–related diabetes induced by antineoplastic drugs: two case reports and a literature review

“…PI3K has four subtypes (α, β, γ, and δ); the α subtype mediates most of the metabolic effects of the PI3K pathway, including insulin signaling in muscle, liver, and adipose tissues ( 26 ). The inhibition of the PI3K pathway blocks glucose uptake by skeletal and adipose tissues and promotes glycogen breakdown and liver gluconeogenesis, leading to hyperinsulinemia, hyperglycemia, and insulin resistance ( 27 ), is also the pathogenesis of type 2 diabetes ( 28 ).…”