Sweet and simple as syrup: A review and guidance for use of novel antihyperglycemic agents for post-transplant diabetes mellitus and type 2 diabetes mellitus after kidney transplantation

Uncontrolled type 2 diabetes mellitus (T2DM) and post-transplant diabetes mellitus (PTDM) increase morbidity and mortality after kidney transplantation. Conventional strategies for diabetes management in this population include metformin, sulfonylureas, meglitinides and insulin. Limitations with these agents, as well as promising new antihyperglycemic agents, create a need and opportunity to explore additional options for transplant diabetes pharmacotherapy. Novel agents including sodium glucose co-transporter 2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP1RA), and dipeptidyl peptidase IV inhibitors (DPP4i) demonstrate great promise for T2DM management in the non-transplant population. Moreover, many of these agents possess renoprotective, cardiovascular, and/or weight loss benefits in addition to improved glucose control while having reduced risk of hypoglycemia compared with certain other conventional agents. This comprehensive review examines available literature evaluating the use of novel antihyperglycemic agents in kidney transplant recipients (KTR) with T2DM or PTDM. Formal grading of recommendations assessment, development, and evaluation (GRADE) system recommendations are provided to guide incorporation of these agents into post-transplant care. Available literature was evaluated to address the clinical questions of which agents provide greatest short- and long-term benefits, timing of novel antihyperglycemic therapy initiation after transplant, monitoring parameters for these antihyperglycemic agents, and concomitant antihyperglycemic agent and immunosuppression regimen management. Current experience with novel antihyperglycemic agents is primarily limited to single-center retrospective studies and case series. With ongoing use and increasing comfort, further and more robust research promises greater understanding of the role of these agents and place in therapy for kidney transplant recipients.