Management of post-transplant diabetes: immunosuppression, early prevention, and novel antidiabetics

Abstract

Post-transplant diabetes mellitus (PTDM) shows a relationship with risk factors including obesity and tacrolimus-based immunosuppression, which decreases pancreatic insulin secretion. Several of the sodium-glucose-linked transporter 2 inhibitors (SGLT2is) and glucagon-like peptide 1 receptor agonists (GLP1-RAs) dramatically improve outcomes of individuals with type 2 diabetes with and without chronic kidney disease, which is, as heart failure and atherosclerotic cardiovascular disease, differentially affected by both drug classes (presumably). Here, we discuss SGLT2is and GLP1-RAs in context with other PTDM management strategies, including modification of immunosuppression, active lifestyle intervention, and early postoperative insulin administration. We also review recent studies with SGLT2is in PTDM, reporting their safety and antihyperglycemic efficacy, which is moderate to low, depending on kidney function. Finally, we reference retrospective case reports with GLP1-RAs that have not brought forth major concerns, likely indicating that GLP1-RAs are ideal for PTDM patients suffering from obesity. Although our article encompasses PTDM after solid organ transplantation in general, data from kidney transplant recipients constitute the largest proportion. The PTDM research community still requires data that treating and preventing PTDM will improve clinical conditions beyond hyperglycemia. We therefore suggest that it is time to collaborate, in testing novel antidiabetics among patients of all transplant disciplines.

Keywords: atherosclerosis; cardiovascular diseases; chronic; diabetes mellitus; glucagon-like peptide-1 receptor; glucose; hypoglycemic agents; immunosuppression; insulin; prospective studies; renal insufficiency; retrospective studies; type 2.

Figure 1

Messages derived from two prospective SGLT2 inhibitor studies in PTDM patients. EMPA‐Renal Tx study (Oslo, a = left panel [112]) and EMPTRA‐DM study (Vienna, b = right panel [111]). Abbreviations: LDL = low‐density lipoprotein, SMBG = self‐monitored blood glucose

Figure 2

Potential benefits of SGLT2 inhibitors and GLP1R agonists in solid organ transplant patients. Abbreviations: PTDM = post‐transplantation diabetes mellitus, SGLT2i = sodium–glucose‐linked transporter 2 inhibitor, GLP1‐RA = glucagon‐like 1 receptor agonist, LDL = low‐density lipoprotein, TGF = tubuloglomerular feedback, SNS = sympathetic nervous system