Efficacy and Safety of Dipeptidyl Peptidase-4 Inhibitors in Kidney Transplant Recipients with Post-transplant Diabetes Mellitus (PTDM)- a Systematic Review and Meta-Analysis

Abstract

Background: Kidney transplant recipients may develop post-transplant diabetes mellitus (PTDM). Dipeptidyl peptidase 4(DPP-4) inhibitors are evolving agents in the management of patients with diabetes mellitus. Aims: To evaluate the efficacy and safety of DPP-4 inhibitors in the management of post-transplant diabetes mellitus (PTDM) in renal transplant recipients. Methods: We performed a systematic search of the electronic databases using keys words and Mesh terms. Data were extracted and reviewed using structured proforma. A comprehensive review of the eligible studies was performed independently by each of two reviewers; conflicts were resolved by the third reviewer. The primary efficacy endpoint was the difference in glycosylated hemoglobin (HbA1c) comparing any of the DPP-4 inhibitors to either placebo or other hypoglycaemic agent. The primary safety endpoints were the worsening of graft functions and change in Tacrolimus trough level. We performed the Random effect model using standardised mean difference. Results: We identified seven studies that were eligible for the systematic review; only one study compared Sitagliptin to insulin Glargine. One study involved head to head comparison of three DPP-4 inhibitors. The other five studies were pooled in the meta-analysis. DPP-4 inhibitors had a favourable glycemic effect as measured by HbA1c when compared to either placebo or oral anti-hyperglycemic medications (standardised mean difference in HbA1c = -0.993, 95% CI= -1.303 to -0.683, P=0.001). DPP-4 inhibitors use did not result in significant change in eGFR ((standardised mean difference = 0.147, 95% CI= -0.139 - 0.433, p=0.312).) nor Tacrolimus level (standardised Mean Difference= 0.152, 95% CI= -0.172 to 0.477, P=0.354). Conclusion: Current evidence supports the short term efficacy and safety of DDP-4 inhibitor agents in the management of post transplantation diabetes mellitus (PTDM) in kidney transplant recipients. However, more RCTs are required to investigate the long-term safety and efficacy of these agents in kidney transplant recipients.

Effects of Dapagliflozin and Sitagliptin on Insulin Resistant and Body Fat Distribution in Newly Diagnosed Type 2 Diabetic Patients

“…Among these novel anti-diabetic medications, sodiumglucose cotransporter-2 (SGLT-2) inhibitor and dipeptidyl peptidase-4 (DPP-4) inhibitor are the ones that are currently widely used [5][6][7][8][9]. Compared to prior anti-diabetic medications (e.g., sulfonylurea), these medications not only effectively reduce blood glucose level, but are also associated with lower risk of hypoglycemia and have reported better clinical outcomes [10,11]. The mechanisms underlying these benefits are likely multifactorial.…”

Diabetes mellitus in dialysis and renal transplantation

“…A 2019 meta-analysis of five studies investing gliptin use in patients with PTDM after renal transplant suggested that they are safe and effective at reducing HbA1c without affecting eGFR or tacrolimus level. 102 …”

“…101 A 2019 meta-analysis of five studies investing gliptin use in patients with PTDM after renal transplant suggested that they are safe and effective at reducing HbA1c without affecting eGFR or tacrolimus level. 102 GLP-1 analogues GLP-1 analogues mimic the incretin GLP-1 to stimulate glucose-dependent insulin secretion.…”

Combination of vitamin D and dipeptidyl peptidase-4 inhibitors (VIDPP-4i) as an immunomodulation therapy for autoimmune diabetes

“…In fact, VIDPP-4i may modulate T-cell differentiation and promote immune tolerance by selectively inhibiting effector T cells and upregulating Tregs, potentially allowing for reduction of immunosuppressant dose and immunosuppression-related toxicity. In this context, the use of DPP-4i may also be advantageous in terms of reduced glucotoxicity and preservation of beta-cell function among patients with T1D who underwent kidney, pancreas or islet transplantation, and patients with post-transplant diabetes [233].…”