In persons with type 2 diabetes without established cardiovascular complications data are lacking on the comparative effectiveness of commonly used glucose-lowering medications, when added to metformin, with respect to glycemic outcomes as well as microvascular and cardiovascular disease outcomes. The GRADE trial compared the ability of four glucose-lowering remedies to achieve and maintain a defined glycated hemoglobin target and to protect the participant from microvascular and macrovascular complications. In this article, we comment on the relevance of this trial with specific attention for the notion that GLP-1 receptor agonists seem to have a primary preventive effect.