Chances and risks of sodium-glucose cotransporter 2 inhibitors in solid organ transplantation: A review of literatures

Abstract

Solid organ transplantation offers life-saving treatment for patients with end-organ dysfunction. Patient survival and quality of life have improved over the past few decades as a result of pharmacological development, expansion of the donor pool, technological advances and standardization of practices related to transplantation. Still, transplantation is associated with cardiovascular complications, of which post-transplant diabetes mellitus (PTDM) is one of the most important. PTDM increases mortality, which is best documented in patients who have received kidney and heart transplants. PTDM results from traditional risk factors seen in patients with type 2 diabetes mellitus, but also from specific post-transplant risk factors such as metabolic side effects of immunosuppressive drugs, post-transplant viral infections and hypomagnesemia. Oral hypoglycaemic agents are the first choice for the treatment of type 2 diabetes mellitus in non-transplanted patients. However, the evidence on the safety and efficacy of oral hypoglycaemic agents in transplant recipients is limited. The favourable risk/benefit ratio, which is suggested by large-scale and long-term studies on new glucose-lowering drug classes such as glucagon-like peptide 1 receptor agonists and sodium-glucose cotransporter 2 inhibitors, makes studies warranted to assess the potential role of these agents in the management of PTDM.

New-Onset Diabetes Mellitus in Post-renal Transplant Patients on Tacrolimus and Mycophenolate: A Systematic Review

“…In the CANVAS research, participants who were randomly assigned to the canagliflozin group experienced a lower incidence of cardiovascular events. The study also revealed that canagliflozin-assigned subjects were less likely to have end-stage renal disease, a decline in eGFR, or albuminuria progression [11].…”

“…In the CANVAS research, participants who were randomly assigned to the canagliflozin group experienced a lower incidence of cardiovascular events. The study also revealed that canagliflozin-assigned subjects were less likely to have end-stage renal disease, a decline in eGFR, or albuminuria progression [ 11 ]. According to an RCT trial results, individuals with bilateral nephrectomies showed decreased de novo glucose production for increased glucose loss caused by SGLT2 inhibitors indicating that the hepatic renal axis is deranged due to lack of efferent nerve stimulation [ 26 ].…”

“…The most modifiable risk factor for the development of PTDM is immunosuppression, however, to balance this risk against the risk of rejection, a risk vs. benefit analysis is needed [ 11 ]. Glucose-lowering medications have been shown to improve PTDM, but extensive research is needed to determine their safety and effectiveness [ 12 , 13 ].…”

Novel Drugs for the Management of Diabetes Kidney Transplant Patients: A Literature Review

“…However, the benefits published in these studies are also aligned with those demonstrated in the general population [ 77 , 78 , 79 , 80 ]. Nevertheless, the most frequently observed side effects are precisely effects that could be potentially harmful to this population profile, such as severe or recurrent urinary tract infections and impaired kidney function [ 81 , 82 ]. Table 3 and Table 4 summarize the effects observed in the studies conducted to date.…”

“…Acute renal failure could be another disadvantage of these drugs, which in some cases forces their withdrawal and in others could delay or discourage their initiation [ 92 ]. Some studies have shown unchanging renal function despite the onset of SGLT2i, [ 81 , 84 , 86 , 87 , 89 , 90 ], while other studies showed an early impairment of renal function (eGFR-dippers) (18–14%), but followed by later stabilization [ 85 , 88 , 93 ] or an even slower decline in renal function with respect to the control group [ 94 ].…”