Unveiling the potential of prodrug and drug-conjugate strategies in treatment of diabetes mellitus and its complications

The 2021 statistics from the International Diabetes Federation reveals that approximately 537 million adults between the ages of 20 and 79 are currently coping with diabetes, highlighting the pressing demand for innovative treatments. To expedite this process, it is crucial to learn from previous failures in drug development. One established method for enhancing the biological, pharmacokinetic or the physicochemical properties of potent drug candidates is through the use of prodrugs. Prodrugs have demonstrated their effectiveness in surmounting challenges related to a drug’s efficacy during the phases of drug research and development. This review distinctly emphasizes the role of the prodrug strategy in facilitating drug discovery to address concerns associated with diabetes mellitus (DM). It emphasizes the utilization of diverse prodrug approaches in the management of DM and the complications associated with it by categorizing them into ester/ether prodrugs, phosphonic diamide prodrugs, biguanide prodrugs, nitric oxide releasing prodrugs, mutual prodrugs, peptide-linked prodrugs, as well as different types of drug conjugate approaches. It specifically elaborates a range of prodrug systems developed between the years 2000 and 2023 for achieving effective drug delivery in the context of DM.