Tirzepatide, a dual GIP/GLP-1 receptor agonist, reduced protein spillage in urine by 68.9% over six months in 15 overweight Fabry disease patients already receiving optimal treatment. This dramatic reduction—from 1.11 to 0.35 grams per day—occurred alongside stable kidney function and significant decreases in cardiac stress markers including NT-proBNP (33.3% reduction) and troponin T (14.3% reduction). This finding represents a paradigm shift for treating Fabry disease, a rare genetic disorder where enzyme deficiency causes progressive kidney and heart damage. Current therapies focus on enzyme replacement and blood pressure control, yet many patients continue losing kidney function despite treatment. The dual incretin approach offers an entirely new mechanism—targeting inflammation and fibrosis pathways rather than just the underlying enzyme defect. While the small sample size and short duration limit generalizability, the magnitude of benefit is striking for a condition with limited therapeutic options. This could establish a template for repurposing metabolic medications in rare diseases, particularly given tirzepatide's excellent safety profile and the urgent need for nephroprotective interventions in genetic kidney disorders.