# Hyperglycaemia (PI3K/AKT inhibitor class effect)

Source: https://onco.cc/terms/hyperglycaemia/  
OnCo record `hyperglycaemia` (Term). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

High blood sugar as a side effect of drugs that block the PI3K/AKT pathway, because the same pathway carries insulin's signal in muscle and liver. It is the main reason these otherwise effective breast cancer drugs are hard to give.

## Summary

Alpelisib causes hyperglycaemia in about 65% of patients (grade 3-4 in a third), capivasertib and everolimus less often; steroids and some immunotherapy-induced diabetes also raise glucose. Management is screening for pre-diabetes, metformin (often prophylactic), SGLT2 inhibitors, dietary carbohydrate restriction and dose modification; mutant-selective PI3Kα inhibitors (inavolisib, RLY-2608) were designed to reduce it. Hyperglycaemia is a textbook on-target toxicity: the pathway that drives PIK3CA-mutant cancers is the same one insulin uses, and the ketogenic-diet-plus-PI3K-inhibitor hypothesis arose directly from this observation.

## Fields

- Kind: Term
- Last checked: 2026-09-09
- Also known as: hyperglycemia; high blood sugar; raised glucose; glucose monitoring; PI3K inhibitor toxicity; PI3Kα inhibitor; metformin prophylaxis; SGLT2 inhibitor; ketogenic diet with PI3K inhibitors

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Hyperglycemia
- Wikipedia: https://en.wikipedia.org/wiki/Hyperglycemia

## Connected records

- terms: [Dose reduction, interruption and discontinuation](https://onco.cc/terms/dose-modification/), [Endocrine resistance](https://onco.cc/terms/endocrine-resistance/), [Therapeutic index (therapeutic window)](https://onco.cc/terms/therapeutic-index/)
- fronts: [Supportive Care & Survivorship](https://onco.cc/fronts/supportive-care/), [Targeted Therapy](https://onco.cc/fronts/targeted-therapy/)
- drugs: [Alpelisib](https://onco.cc/drugs/alpelisib/), [Capivasertib](https://onco.cc/drugs/capivasertib/), [Everolimus](https://onco.cc/drugs/everolimus/), [Inavolisib](https://onco.cc/drugs/inavolisib/)
- biomarkers: [AKT1 E17K mutation](https://onco.cc/biomarkers/akt1-e17k/), [PIK3CA mutation](https://onco.cc/biomarkers/pik3ca-hotspot-mutation/)

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