Efficacy and Safety of the Utilization of Dipeptidyl Peptidase IV Inhibitors in Diabetic Patients with Chronic Kidney Disease: A Meta-Analysis of Randomized Clinical Trials

Overview

Journal Diabetes Metab Syndr Obes

Publisher Dove Medical Press

Specialty Endocrinology

Date 2024 Mar 28

PMID 38545319

Authors

Moeber M Mahzari

Muhannad Qirnas Alqirnas

Moustafa S Alhamadh

Faisal Alrasheed

Abdulrahman Yousef Alhabeeb

Wedad Al Madani

Hussain Aldera

Affiliations

Soon will be listed here.

Abstract

Aim: To assess the efficacy and safety of Dipeptidyl Peptidase IV (DPP-4) inhibitors in patients with Type-2 Diabetes Mellitus (T2DM) and chronic kidney disease (CKD) using level 1 evidence.

Methods: The Cochrane and PubMed databases were searched from inception until January 1, 2022. RCTs that studied the efficacy and safety of DPP-4 inhibitors in diabetic patients with CKD were included. The primary efficacy outcome was assessed as the mean difference between HbA1c at the beginning and the end of each study for each arm, and the primary safety outcome was assessed as the incidence of adverse events and severe adverse events in each study.

Results: Twenty-one studies satisfied the pre-defined eligibility criteria. In assessing the efficacy of DPP-4 inhibitors in the treatment of T2DM and CKD, a total of 2917 patients under the DPP-4 inhibitors group and 2377 patients under the control group were included; The mean difference between the HbA1c of DPP-4 Inhibitor and the control group was -0.5295 with a 95% CI of -0.5337 to -0.5252. The included studies had high heterogeneity p < 0.00001 and I = 99%. In assessing the safety outcome and tolerability of DPP-4 inhibitors, a total of 8138 patients under the DPP-4 inhibitors group and 7517 patients under the control group were included; the odds ratio of adverse events between both groups was 0.9967 with a 95% CI of 0.9967 to 1.1047. The included studies had low heterogeneity p = 0.25 and I = 15%. The overall effect, Z = 0.06 (p = 0.95), was insignificant.

Conclusion: Patients suffering from both T2DM and CKD exhibited a significantly enhanced glycemic control when treated with DPP-4 inhibitors in comparison to the control group. Furthermore, no significant difference in the incidence of adverse events was observed between the DPP-4 inhibitors and the control group.

References

Zhang X, Zhang G, Zhang L, Sun C, Liu N, Chen M . Spontaneous rupture of the urinary bladder caused by eosinophilic cystitis in a male after binge drinking: A case report. Medicine (Baltimore). 2018; 96(51):e9170. PMC: 5758155. DOI: 10.1097/MD.0000000000009170. View

Chan J, Scott R, Arjona Ferreira J, Sheng D, Gonzalez E, Davies M . Safety and efficacy of sitagliptin in patients with type 2 diabetes and chronic renal insufficiency. Diabetes Obes Metab. 2008; 10(7):545-55. DOI: 10.1111/j.1463-1326.2008.00914.x. View

Arjona Ferreira J, Corry D, Mogensen C, Sloan L, Xu L, Golm G . Efficacy and safety of sitagliptin in patients with type 2 diabetes and ESRD receiving dialysis: a 54-week randomized trial. Am J Kidney Dis. 2013; 61(4):579-87. DOI: 10.1053/j.ajkd.2012.11.043. View

Ramirez G, Morrison A, Bittle P . Clinical practice considerations and review of the literature for the Use of DPP-4 inhibitors in patients with type 2 diabetes and chronic kidney disease. Endocr Pract. 2013; 19(6):1025-34. DOI: 10.4158/EP12306.RA. View

Perkovic V, Heerspink H, Chalmers J, Woodward M, Jun M, Li Q . Intensive glucose control improves kidney outcomes in patients with type 2 diabetes. Kidney Int. 2013; 83(3):517-23. DOI: 10.1038/ki.2012.401. View

Thomas M, Cooper M, Zimmet P . Changing epidemiology of type 2 diabetes mellitus and associated chronic kidney disease. Nat Rev Nephrol. 2015; 12(2):73-81. DOI: 10.1038/nrneph.2015.173. View

McGill J, Yki-Jarvinen H, Crowe S, Woerle H, von Eynatten M . Combination of the dipeptidyl peptidase-4 inhibitor linagliptin with insulin-based regimens in type 2 diabetes and chronic kidney disease. Diab Vasc Dis Res. 2015; 12(4):249-57. DOI: 10.1177/1479164115579001. View

Park H, Park C, Kim Y, Rascati K . Efficacy and safety of dipeptidyl peptidase-4 inhibitors in type 2 diabetes: meta-analysis. Ann Pharmacother. 2012; 46(11):1453-69. DOI: 10.1345/aph.1R041. View

Kaku K, Ishida K, Shimizu K, Achira M, Umeda Y . Efficacy and safety of trelagliptin in Japanese patients with type 2 diabetes with severe renal impairment or end-stage renal disease: Results from a randomized, phase 3 study. J Diabetes Investig. 2019; 11(2):373-381. PMC: 7078116. DOI: 10.1111/jdi.13126. View

10.

Groop P, Del Prato S, Taskinen M, Owens D, Gong Y, Crowe S . Linagliptin treatment in subjects with type 2 diabetes with and without mild-to-moderate renal impairment. Diabetes Obes Metab. 2014; 16(6):560-8. PMC: 4288982. DOI: 10.1111/dom.12281. View

11.

Drucker D, Nauck M . The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet. 2006; 368(9548):1696-705. DOI: 10.1016/S0140-6736(06)69705-5. View

12.

Zelnick L, Weiss N, Kestenbaum B, Robinson-Cohen C, Heagerty P, Tuttle K . Diabetes and CKD in the United States Population, 2009-2014. Clin J Am Soc Nephrol. 2017; 12(12):1984-1990. PMC: 5718269. DOI: 10.2215/CJN.03700417. View

13.

Ito M, Abe M, Okada K, Sasaki H, Maruyama N, Tsuchida M . The dipeptidyl peptidase-4 (DPP-4) inhibitor vildagliptin improves glycemic control in type 2 diabetic patients undergoing hemodialysis. Endocr J. 2011; 58(11):979-87. DOI: 10.1507/endocrj.ej11-0025. View

14.

Otsuki H, Kosaka T, Nakamura K, Shimomura F, Kuwahara Y, Tsukamoto T . Safety and efficacy of teneligliptin: a novel DPP-4 inhibitor for hemodialysis patients with type 2 diabetes. Int Urol Nephrol. 2013; 46(2):427-32. DOI: 10.1007/s11255-013-0552-6. View

15.

Laakso M, Rosenstock J, Groop P, Barnett A, Gallwitz B, Hehnke U . Treatment with the dipeptidyl peptidase-4 inhibitor linagliptin or placebo followed by glimepiride in patients with type 2 diabetes with moderate to severe renal impairment: a 52-week, randomized, double-blind clinical trial. Diabetes Care. 2015; 38(2):e15-7. DOI: 10.2337/dc14-1684. View

16.

Cornel J, Bakris G, Stevens S, Alvarsson M, Bax W, Chuang L . Effect of Sitagliptin on Kidney Function and Respective Cardiovascular Outcomes in Type 2 Diabetes: Outcomes From TECOS. Diabetes Care. 2016; 39(12):2304-2310. DOI: 10.2337/dc16-1415. View

17.

Yki-Jarvinen H, Rosenstock J, Duran-Garcia S, Pinnetti S, Bhattacharya S, Thiemann S . Effects of adding linagliptin to basal insulin regimen for inadequately controlled type 2 diabetes: a ≥52-week randomized, double-blind study. Diabetes Care. 2013; 36(12):3875-81. PMC: 3836100. DOI: 10.2337/dc12-2718. View

18.

Kothny W, Shao Q, Groop P, Lukashevich V . One-year safety, tolerability and efficacy of vildagliptin in patients with type 2 diabetes and moderate or severe renal impairment. Diabetes Obes Metab. 2012; 14(11):1032-9. DOI: 10.1111/j.1463-1326.2012.01634.x. View

19.

Giorda C, Nada E, Tartaglino B . Pharmacokinetics, safety, and efficacy of DPP-4 inhibitors and GLP-1 receptor agonists in patients with type 2 diabetes mellitus and renal or hepatic impairment. A systematic review of the literature. Endocrine. 2014; 46(3):406-19. DOI: 10.1007/s12020-014-0179-0. View

20.

Perl S, Cook W, Wei C, Iqbal N, Hirshberg B . Saxagliptin Efficacy and Safety in Patients With Type 2 Diabetes and Moderate Renal Impairment. Diabetes Ther. 2016; 7(3):527-35. PMC: 5014790. DOI: 10.1007/s13300-016-0184-9. View