Unlocking Therapeutic Synergy: Tailoring Drugs for Comorbidities such as Depression and Diabetes through Identical Molecular Targets in Different Cell Types

Research in the field of pharmacology aims to generate new treatments for pathologies. Nowadays, there are an increased number of chronic disorders that severely and durably handicap many patients. Among the most widespread pathologies, obesity, which is often associated with diabetes, is constantly increasing in incidence, and in parallel, neurodegenerative and mood disorders are increasingly affecting many people. For years, these pathologies have been so frequently observed in the population in a concomitant way that they are considered as comorbidities. In fact, common mechanisms are certainly at work in the etiology of these pathologies. The main purpose of this review is to show the value of anticipating the effect of baseline treatment of a condition on its comorbidity in order to obtain concomitant positive actions. One of the implications would be that by understanding and targeting shared molecular mechanisms underlying these conditions, it may be possible to tailor drugs that address both simultaneously. To this end, we firstly remind readers of the close link existing between depression and diabetes and secondly address the potential benefit of the pleiotropic actions of two major active molecules used to treat central and peripheral disorders, first a serotonin reuptake inhibitor (Prozac (R)) and then GLP-1R agonists. In the second part, by discussing the therapeutic potential of new experimental antidepressant molecules, we will support the concept that a better understanding of the intracellular signaling pathways targeted by pharmacological agents could lead to future synergistic treatments targeting solely positive effects for comorbidities.