Design of Improved Antidiabetic Drugs: A Journey from Single to Multitarget Agents.

Multifactorial diseases exhibit a complex pathophysiology with several factors contributing to their pathogenesis and development. Examples of such disorders are neurodegenerative (e. g. Alzheimer's, Parkinson's) and cardiovascular diseases (e. g. atherosclerosis, metabolic syndrome, diabetes II). Traditional therapeutic approaches with single-target drugs have been proven, in many cases, unsatisfactory for the treatment of multifactorial diseases such as diabetes II. The well-established by now strategy of multitarget drugs is constantly gaining interest and momentum, as a more effective approach. The development of pharmacomolecules able to simultaneously modulate multiple relevant-to-the-disease targets has already several successful examples in various fields and has, as such, inspired the design of multitarget antidiabetic agents; this review highlights the design aspect and efficacy of this approach for improved antidiabetics by presenting several examples of successful pharmacophore combinations in (multitarget) agents that modulate two or more molecular targets involved in diabetes II, resulting in a superior antihyperglycemic profile.