Diabetic kidney disease (DKD), one of the most common and severe microvascular complications of diabetes, is the leading cause of chronic kidney disease and end-stage kidney disease worldwide. Since the development of renin-angiotensin system inhibition nearly three decades ago, no new therapeutic agents have received regulatory approval for treatment of DKD. Glucagon like peptide-1 (GLP-1) receptor agonists, a class of newer anti-hyperglycemic agents, have shown promise for prevention of DKD onset and progression. This perspective summarizes clinical and experimental observations to give insight into biological mechanisms beyond glycemic control, such as natriuresis and anti-inflammatory actions, for preservation of kidney function in patients with diabetes.