Management of Diabetes Mellitus in Normal Renal Function, Renal Dysfunction and Renal Transplant Recipients, Focusing on Glucagon-Like Peptide-1 Agonist: A Review Based upon Current Evidence

Abstract

Diabetes Mellitus (DM) is a leading cause of both Cardiovascular Disease (CVD) and End-stage Renal Disease (ESRD). After 2008, there has been much evidence presented, and recently the guidelines for sugar control have changed to focus on being more disease orientated. GLP-1 Receptor Agonists (GLP-1R) and sodium glucose cotransporter-2 inhibitors are suggested as the first line towards fighting all DM, CVD and ESRD. However, the benefits of GLP-1R in organ transplantation recipients remain very limited. No clinical trials have been designed for this particular population. GLP-1R, a gastrointestinal hormone of the incretin family, possesses antidiabetic, antihypertensive, anti-inflammatory, anti-apoptotic and immunomodulatory actions. There are few drug–drug interactions, with delayed gastric emptying being the major concern. The trough level of tacrolimus may not be significant but should still be closely monitored. There are some reasons which support GLP-1R in recipients seeking glycemic control. Post-transplant DM is due to an impaired β-cell function and glucose-induced glucagon suppression during hyperglycemia, which can be reversed by GLP-1R. GLP-1R infusion tends to relieve immunosuppressant related toxicity. Until now, in some cases, glycemic control and body weight reduction can be anticipated with GLP-1R. Additional renal benefits have also been reported. Side effects of hypoglycemia and gastrointestinal discomfort were rarely reported. In conclusion, GLP-1R could be implemented for recipients while closely monitoring their tacrolimus levels and any potential side effects. Any added benefits, in addition to sugar level control, still require more well-designed studies to prove their existence.

Effectiveness and safety of glucagon‐like peptide‐1 receptor agonist in a cohort of kidney transplant recipients

“…However, there is little evidence regarding their efficacy in KT. [1][2][3] We present a retrospective cohort study of 50 stable KT recipi- Maintenance immunosuppressive therapy with steroids (95%), tacrolimus (100%), mycophenolate (95%), and everolimus (2.5%) was used. Semaglutide was the GLP-1RA most commonly prescribed (47.5%), followed by liraglutide (32.5%) and dulaglutide (20%).…”

“…These findings have been reported in the general population and may be due to the natriuretic and vasodilator effects of GLP-1RA. 2,3 It is related to a reduction of intraglomerular pressure and as a consequence, proteinuria decreases. 2,3 Additionally, as previously reported, body weight was reduced (-2.4 kg at 6 months, p = .006 and -3 kg at 12 months, P = .041).…”

“…2,3 It is related to a reduction of intraglomerular pressure and as a consequence, proteinuria decreases. 2,3 Additionally, as previously reported, body weight was reduced (-2.4 kg at 6 months, p = .006 and -3 kg at 12 months, P = .041). This effect can be explained because GLP-1RA delays gastric emptying and promotes satiety.…”

“…This effect can be explained because GLP-1RA delays gastric emptying and promotes satiety. 2,3 Obesity is related to an increased risk of death and graft failure. 4 Thus, the use of GLP-1RA may offer survival advantages in KT.…”

Short-Term Treatment of Metformin and Glipizide on Oxidative Stress, Lipid Profile and Renal Function in a Rat Model with Diabetes Mellitus

“…Furthermore, DM is the major reason for end-stage renal disease (ESRD). Controlling the glucose level is the best method to avoid diabetic kidney diseases [20]. Diabetic kidney disease affects about 35% of the diabetic population.…”