The term diabetes mellitus includes a group of metabolic disorders characterized by hyperglycemia with secondary damage to multiple organ systems. The way to improve this crucial situation is to find better drugs for an early treatment of the disease. The clinical trials, is so far, the best procedure to offer more efficient treatments to the increasing diabetic populations. This paper is an update revision about one of the most important diseases worldwide. We analyzed some historical and pathological aspects of the disease, mainly clinic, and diagnostic, and treatment aspects useful in the clinical practice. We also report information about several clinical trials in which our research group has been participating since about two decades; eight of them are listed in this work.