Moore Heather N, Goncalves Marcus D, Johnston Abigail M, Mayer Erica L, Rugo Hope S, Gradishar William J, Zylla Dylan M, Bergenstal Richard M
Duke Cancer Institute, Duke University, Durham, NC.
Weill Department of Medicine, Weill Cornell Medicine, New York, NY.
Clin Breast Cancer. 2025 Jan;25(1):1-11. doi: 10.1016/j.clbc.2024.09.017. Epub 2024 Sep 28.
Hyperglycemia is a common adverse event (AE) associated with phosphatidylinositol-3-kinase inhibitors (PI3Kis) and considered an on-target effect. Presence of hyperglycemia is associated with poor outcomes in patients with cancer, and there is need for further refinement of hyperglycemia prevention and mitigation strategies in patients receiving PI3Kis. In this review, the authors highlight effective strategies for preventing PI3Ki-induced hyperglycemia before and during treatment as well as hyperglycemia management. Prior to initiating treatment with PI3Ki, identify baseline risk factors of patients at increased risk for developing hyperglycemia, which include older age, obesity, and glycosylated hemoglobin (HbA1c) 5.7%-6.4% (prediabetes or Type 2 diabetes). To prevent new-onset hyperglycemia, optimize blood glucose, and recommend a low-carbohydrate (60-130 g/day) diet along with regular exercise to all patients prior to initiating the PI3Ki. Prophylactic metformin may be considered in all patients starting a PI3Ki with HbA1c ≤6.4%. Although existing recommendations support monitoring fasting blood glucose (FBG) once weekly (twice-weekly for intermediate-risk, daily for high-risk patients) and HbA1c every 3 months upon initiation of PI3Ki, more frequent FBG monitoring may be considered for prompt detection of hyperglycemia. Experts also recommend considering postprandial glucose monitoring because it is an early indicator of glucose intolerance. If hyperglycemia develops, metformin (first-line) and/or sodium glucose co-transporter 2 inhibitors or thiazolidinediones (second-/third-line) are the preferred agents; consider early referral to an endocrinologist. In conclusion, hyperglycemia is a common but manageable AE associated with PI3Kis. Multidisciplinary approach to the prevention, monitoring, and management of hyperglycemia optimizes patient care and allows patients to maintain therapy on PI3Ki.
高血糖是与磷脂酰肌醇-3-激酶抑制剂（PI3Kis）相关的常见不良事件（AE），被认为是一种靶向效应。高血糖的存在与癌症患者的不良预后相关，因此需要进一步完善接受PI3Kis治疗患者的高血糖预防和缓解策略。在本综述中，作者强调了在治疗前和治疗期间预防PI3Ki诱导的高血糖以及高血糖管理的有效策略。在开始使用PI3Ki治疗之前，识别发生高血糖风险增加的患者的基线风险因素，包括老年、肥胖和糖化血红蛋白（HbA1c）5.7%-6.4%（糖尿病前期或2型糖尿病）。为预防新发高血糖，优化血糖，并在开始使用PI3Ki之前向所有患者推荐低碳水化合物（60-130克/天）饮食以及规律运动。对于所有开始使用HbA1c≤6.4%的PI3Ki的患者，可考虑预防性使用二甲双胍。尽管现有建议支持在开始使用PI3Ki后每周监测一次空腹血糖（FBG）（中度风险患者每周两次，高风险患者每天一次），每3个月监测一次HbA1c，但为了及时发现高血糖，可考虑更频繁地监测FBG。专家还建议考虑监测餐后血糖，因为它是葡萄糖不耐受的早期指标。如果发生高血糖，二甲双胍（一线）和/或钠-葡萄糖协同转运蛋白2抑制剂或噻唑烷二酮类药物（二线/三线）是首选药物；考虑尽早转诊给内分泌科医生。总之，高血糖是与PI3Kis相关的常见但可管理的AE。多学科方法用于高血糖的预防、监测和管理可优化患者护理，并使患者能够维持PI3Ki治疗。
