In the METALLICA trial, for patients with HR-positive/HER2-negative advanced BC and normal or prediabetic status (baseline HbA1c, <6.5%) receiving alpelisib + ET, prophylactic metformin (500 mg BID, escalating to 1000 mg BID if no GI intolerance occurred) significantly reduced hyperglycemia risk60. The gene discussed is ERBB2; the disease is Hyperglycemia.