Generic placeholder image

Current Diabetes Reviews


ISSN (Print): 1573-3998
ISSN (Online): 1875-6417

Systematic Review Article

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

Author(s): Tarek Samy Abdelaziz*, Ahmed Yamany Ali and Moataz Fatthy

Volume 16, Issue 6, 2020

Page: [580 - 585] Pages: 6

DOI: 10.2174/1573399815666190321144310

Price: $65


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.

Aim: 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.

Keywords: Dipeptidyl-peptidase IV inhibitors, hypoglycemic agents, transplantation, diabetes mellitus, gliptins, meta-analysis.

Cosio FG, Pesavento TE, Osei K, Henry ML, Ferguson RM. Post-transplant diabetes mellitus: increasing incidence in renal allograft recipients transplanted in recent years. Kidney Int 2001; 59(2): 732-7.
[] [PMID: 11168956]
Kasiske BL, Snyder JJ, Gilbertson D, Matas AJ. Diabetes mellitus after kidney transplantation in the United States. Am J Transplant 2003; 3(2): 178-85.
[] [PMID: 12603213]
Sharif A, Hecking M, de Vries APJ, et al. Proceedings from an international consensus meeting on posttransplantation diabetes mellitus: recommendations and future directions. Am J Transplant 2014; 14(9): 1992-2000.
[] [PMID: 25307034]
American Diabetes Association. Standards of medical care in diabetes--2013. Diabetes Care 2013; 36(Suppl. 1): S11-66.
[] [PMID: 23264422]
Ojo AO. Cardiovascular complications after renal transplantation and their prevention. Transplantation 2006; 82(5): 603-11.
[] [PMID: 16969281]
Sulanc E, Lane JT, Puumala SE, Groggel GC, Wrenshall LE, Stevens RB. New-onset diabetes after kidney transplantation: an application of 2003 International Guidelines. Transplantation 2005; 80(7): 945-52.
[] [PMID: 16249743]
Midtvedt K, Hjelmesaeth J, Hartmann A, et al. Insulin resistance after renal transplantation: the effect of steroid dose reduction and withdrawal. J Am Soc Nephrol 2004; 15(12): 3233-9.
[] [PMID: 15579527]
Hjelmesaeth J, Müller F, Jenssen T, Rollag H, Sagedal S, Hartmann A. Is there a link between cytomegalovirus infection and new-onset posttransplantation diabetes mellitus? Potential mechanisms of virus induced beta-cell damage. Nephrol Dial Transplant 2005; 20(11): 2311-5.
[] [PMID: 16046502]
Vella A. Mechanism of action of DPP-4 inhibitors--new insights. J Clin Endocrinol Metab 2012; 97(8): 2626-8.
[] [PMID: 22869847]
Herman GA, Stevens C, Van Dyck K, et al. Pharmacokinetics and pharmacodynamics of sitagliptin, an inhibitor of dipeptidyl peptidase IV, in healthy subjects: results from two randomized, double-blind, placebo-controlled studies with single oral doses. Clin Pharmacol Ther 2005; 78(6): 675-88.
[] [PMID: 16338283]
Covington P, Christopher R, Davenport M, et al. Pharmacokinetic, pharmacodynamic, and tolerability profiles of the dipeptidyl peptidase-4 inhibitor alogliptin: a randomized, double-blind, placebo-controlled, multiple-dose study in adult patients with type 2 diabetes. Clin Ther 2008; 30(3): 499-512.
[] [PMID: 18405788]
Retlich S, Withopf B, Greischel A, Staab A, Jaehde U, Fuchs H. Binding to dipeptidyl peptidase-4 determines the disposition of linagliptin (BI 1356)--investigations in DPP-4 deficient and wildtype rats. Biopharm Drug Dispos 2009; 30(8): 422-36.
[] [PMID: 19771584]
Fuchs H, Tillement JP, Urien S, Greischel A, Roth W. Concentration-dependent plasma protein binding of the novel dipeptidyl peptidase 4 inhibitor BI 1356 due to saturable binding to its target in plasma of mice, rats and humans. J Pharm Pharmacol 2009; 61(1): 55-62.
[] [PMID: 19126297]
Wells GA, Shea B, O'Connell D, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses 2018.3/1/
Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003; 327(7414): 557-60.
[] [PMID: 12958120]
Pereira TV, Patsopoulos NA, Salanti G, Ioannidis JP. Critical interpretation of Cochran’s Q test depends on power and prior assumptions about heterogeneity. Res Synth Methods 2010; 1(2): 149-61.
[] [PMID: 26061380]
Bae J, Lee MJ, Choe EY, et al. Effects of dipeptidyl peptidase-4 inhibitors on hyperglycemia and blood cyclosporine levels in renal transplant patients with diabetes: a pilot study. Endocrinol Metab (Seoul) 2016; 31(1): 161-7.
[] [PMID: 26754588]
Soliman AR, Fathy A, Khashab S, Shaheen N, Soliman MA. Sitagliptin might be a favorable antiobesity drug for new onset diabetes after a renal transplant. Exp Clin Transplant 2013; 11(6): 494-8.
[] [PMID: 24344941]
Haidinger M, Werzowa J, Hecking M, et al. Efficacy and safety of vildagliptin in new-onset diabetes after kidney transplantation--a randomized, double-blind, placebo-controlled trial. Am J Transplant 2014; 14(1): 115-23.
[] [PMID: 24279801]
Boerner BP, Miles CD, Shivaswamy V. Efficacy and safety of sitagliptin for the treatment of new-onset diabetes after renal transplantation. Int J Endocrinol 2014; 2014617638
[] [PMID: 24817885]
Strøm Halden TA, Åsberg A, Vik K, Hartmann A, Jenssen T. Short-term efficacy and safety of sitagliptin treatment in long-term stable renal recipients with new-onset diabetes after transplantation. Nephrol Dial Transplant 2014; 29(4): 926-33.
[] [PMID: 24452849]
Sanyal D, Gupta S, Das P. A retrospective study evaluating efficacy and safety of linagliptin in treatment of NODAT (in renal transplant recipients) in a real world setting. Indian J Endocrinol Metab 2013; 17(Suppl. 1): S203-5.
[] [PMID: 24251159]
Lane JT, Odegaard DE, Haire CE, Collier DS, Wrenshall LE, Stevens RB. Sitagliptin therapy in kidney transplant recipients with new-onset diabetes after transplantation. Transplantation 2011; 92(10): e56-7.
[] [PMID: 22067216]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy