The hyperglycemia from PI3K/AKT inhibitors is due to insulin resistance, not lack of insulin. Treatment must focus on insulin sensitizers (metformin, SGLT2 inhibitors). Using agents that increase insulin secretion is counterproductive as it can reactivate the PI3K cancer pathway.
For patients sensitive to standard loperamide tablets who experience rebound constipation, the liquid formulation offers more flexible, precise dosing. This allows for better symptom control of diarrhea without overcorrecting and causing constipation, improving overall patient tolerance.
When patients experience a consistent pattern of diarrhea, clinicians should move from a reactive, per-episode dosing strategy to a proactive, scheduled regimen of loperamide. This provides better control and prevents symptoms from escalating, with the option to de-escalate as the patient stabilizes.
While guidelines recommend any second-generation antihistamine for rash prophylaxis, clinical data indicate cetirizine is more effective than others for histamine-mediated cutaneous events caused by drugs. Clinicians should preferentially recommend cetirizine unless a patient has a known preference or intolerance.
Testing for PI3K/AKT alterations at the initial diagnosis of metastatic disease, rather than waiting for progression, provides a crucial window of time. This allows clinicians to implement proactive dietary and medical strategies to mitigate future side effects like hyperglycemia before the targeted therapy is even started.
For select patients who find frequent lab checks for hyperglycemia monitoring to be a significant barrier, a continuous glucose monitor (CGM) can be a practical alternative. While off-label, it provides valuable data for management in patients who might otherwise be non-adherent with monitoring.
When managing drug-induced rash, recurrence is often caused by restarting therapy before the initial rash has completely resolved. Patients may be eager to resume treatment and minimize lingering symptoms, so clinicians must explicitly educate them on the need for full resolution to prevent a cycle of recurrence.