Posttransplant Diabetes Mellitus: Recent Developments in Pharmacological Management of Hyperglycemia

Abstract

Context: The management of solid-organ transplantation is rapidly evolving, and posttransplant diabetes mellitus (PTDM), which is increasingly common, is a barrier to transplant success, adversely impacting infection rates, allograft survival, cardiovascular disease, quality of life, and overall mortality. Currently, the management of PTDM relies primarily on intensified insulin therapy. However, emerging studies report that several noninsulin glucose-lowering agents are safe and effective in improving metabolic control and enhancing treatment adherence. More importantly, their use in PTDM can potentially transform the long-term management of these complex patients, as some glucose-lowering agents may provide benefits beyond glycemic control. For instance, glucagon-like peptide 1 receptor agonists (GLP-1 RA) and sodium-glucose cotransporter 2 (SGLT-2) inhibitors may offer cardiorenal protection, and pioglitazone may treat nonalcoholic fatty liver disease (NAFLD). This review will focus on the pharmacological management of PTDM and the emerging evidence for noninsulin glucose-lowering agents in this population. Evidence acquisition: Evidence from observational studies, randomized controlled trials, and meta-analyses. Evidence synthesis: PTDM adversely affects the outcomes of infection, organ survival, cardiovascular events, and mortality. Insulin therapy has been the drug of choice but is associated with weight gain and hypoglycemia. In contrast, noninsulin agents appear safe and may provide additional benefits, such as cardiorenal protection with SGLT-2 inhibitors and GLP-1 RA, and cardiometabolic benefits with pioglitazone, in patients undergoing solid-organ transplantation. Conclusions: Optimal care of patients with PTDM requires close monitoring and the early involvement of the endocrinologist as part of a multidisciplinary team. Noninsulin glucose-lowering agents will likely play an increasing role as more long-term, controlled studies become available in this setting.