{"entity":{"id":"hyperglycaemia","kind":"term","name":"Hyperglycaemia (PI3K/AKT inhibitor class effect)","aka":["hyperglycemia","high blood sugar","raised glucose","glucose monitoring","PI3K inhibitor toxicity","PI3Kα inhibitor","metformin prophylaxis","SGLT2 inhibitor","ketogenic diet with PI3K inhibitors"],"tldr":"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.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Hyperglycemia","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Hyperglycemia"}],"tags":[],"related":["therapeutic-index","dose-modification","endocrine-resistance"],"cancers":[],"sections":["supportive-care","targeted-therapy"],"technologies":[],"targets":[],"drugs":["alpelisib","capivasertib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Side effects"},"route":"/terms/hyperglycaemia/","neighbours":{"term":[{"id":"dose-modification","kind":"term","name":"Dose reduction, interruption and discontinuation","route":"/terms/dose-modification/"},{"id":"endocrine-resistance","kind":"term","name":"Endocrine resistance","route":"/terms/endocrine-resistance/"},{"id":"therapeutic-index","kind":"term","name":"Therapeutic index (therapeutic window)","route":"/terms/therapeutic-index/"}],"section":[{"id":"supportive-care","kind":"section","name":"Supportive Care & Survivorship","route":"/fronts/supportive-care/"},{"id":"targeted-therapy","kind":"section","name":"Targeted Therapy","route":"/fronts/targeted-therapy/"}],"drug":[{"id":"alpelisib","kind":"drug","name":"Alpelisib","route":"/drugs/alpelisib/"},{"id":"capivasertib","kind":"drug","name":"Capivasertib","route":"/drugs/capivasertib/"},{"id":"everolimus","kind":"drug","name":"Everolimus","route":"/drugs/everolimus/"},{"id":"inavolisib","kind":"drug","name":"Inavolisib","route":"/drugs/inavolisib/"}],"biomarker":[{"id":"akt1-e17k","kind":"biomarker","name":"AKT1 E17K mutation","route":"/biomarkers/akt1-e17k/"},{"id":"pik3ca-hotspot-mutation","kind":"biomarker","name":"PIK3CA mutation","route":"/biomarkers/pik3ca-hotspot-mutation/"}]}}