Risk of Diarrhea in Patients with Type 2 Diabetes Mellitus Treated with Sitagliptin: a Meta-analysis of 30 Randomized Clinical Trials

Overview

Journal Drug Des Devel Ther

Specialty Pharmacology

Date 2014 Nov 25

PMID 25419118

Citations 1

Authors

Qingwei Zhao

Dongsheng Hong

Dongsheng Zheng

Yao Xiao

Baohua Wu

Affiliations

Soon will be listed here.

Abstract

Background: Sitagliptin is an important drug used for diabetes treatment and is used as a monotherapy in diabetic patients. However, there are also reported cases of diarrhea with sitagliptin use. Unfortunately, data concerning the relationship of diarrhea with sitagliptin use in various conditions have yet to be identified. Therefore, the overall incidence and risk of diarrhea with sitagliptin use have not been well defined.

Methods: We conducted searches on Embase, PubMed, and the Cochrane Library databases for relevant randomized controlled trials. Registered relevant trials at the clinical trials registration website were also searched. Statistical analyses were conducted to calculate the overall incidence, odds ratios, and 95% confidence intervals (CI) by using either random-effects or fixed-effect models according to the heterogeneity of the included studies.

Results: A total of 8,891 subjects with diabetes from 30 randomized clinical trials were included in the meta-analysis. The overall incidence of sitagliptin-associated diarrhea was 4.48% (95% CI: 3.59%-5.58%). Compared with the controls, the use of sitagliptin was not associated with a significantly increased risk of diarrhea with an odds ratio of 1.10 (95% CI: 0.78%-1.55%; P=0.58). No evidence of publication bias was observed.

Conclusion: Our study has shown that there is no difference in diarrhea risk between sitagliptin and controlled therapies. Moreover, sitagliptin is not a medicine that potentially increases the risk of diabetic diarrhea. More studies are recommended to further investigate this association.

Citing Articles

Chitosan oligosaccharide improves the therapeutic efficacy of sitagliptin for the therapy of Chinese elderly patients with type 2 diabetes mellitus.

Zhao L, Sun T, Wang L Ther Clin Risk Manag. 2017; 13:739-750.

PMID: 28721055 PMC: 5499789. DOI: 10.2147/TCRM.S134039.

References

Sweeting M, Sutton A, Lambert P . What to add to nothing? Use and avoidance of continuity corrections in meta-analysis of sparse data. Stat Med. 2004; 23(9):1351-75. DOI: 10.1002/sim.1761. View

Lavalle-Gonzalez F, Januszewicz A, Davidson J, Tong C, Qiu R, Canovatchel W . Efficacy and safety of canagliflozin compared with placebo and sitagliptin in patients with type 2 diabetes on background metformin monotherapy: a randomised trial. Diabetologia. 2013; 56(12):2582-92. PMC: 3825495. DOI: 10.1007/s00125-013-3039-1. View

Williams-Herman D, Johnson J, Teng R, Luo E, Davies M, Kaufman K . Efficacy and safety of initial combination therapy with sitagliptin and metformin in patients with type 2 diabetes: a 54-week study. Curr Med Res Opin. 2009; 25(3):569-83. DOI: 10.1185/03007990802705679. View

Jabbour S, Ziring B . Advantages of extended-release metformin in patients with type 2 diabetes mellitus. Postgrad Med. 2011; 123(1):15-23. DOI: 10.3810/pgm.2011.01.2241. View

Bogaert Y, Schrier R . Into the future: prevention of diabetes. Contrib Nephrol. 2011; 170:256-263. DOI: 10.1159/000325781. View

Gallwitz B . Sitagliptin: Profile of a novel DPP-4 inhibitor for the treatment of type 2 diabetes. Drugs Today (Barc). 2007; 43(1):13-25. DOI: 10.1358/dot.2007.43.1.1043909. View

Charbonnel B, Karasik A, Liu J, Wu M, Meininger G . Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin added to ongoing metformin therapy in patients with type 2 diabetes inadequately controlled with metformin alone. Diabetes Care. 2006; 29(12):2638-43. DOI: 10.2337/dc06-0706. View

Zintzaras E, Ioannidis J . Heterogeneity testing in meta-analysis of genome searches. Genet Epidemiol. 2004; 28(2):123-37. DOI: 10.1002/gepi.20048. View

Begg C, Mazumdar M . Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994; 50(4):1088-101. View

10.

Argyrakopoulou G, Doupis J . DPP4 inhibitors: from sitagliptin monotherapy to the new alogliptin-pioglitazone combination therapy. Adv Ther. 2009; 26(3):272-80. DOI: 10.1007/s12325-009-0009-6. View

11.

Rosenstock J, Brazg R, Andryuk P, Lu K, Stein P . Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin added to ongoing pioglitazone therapy in patients with type 2 diabetes: a 24-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Clin Ther. 2006; 28(10):1556-68. DOI: 10.1016/j.clinthera.2006.10.007. View

12.

Moher D, Liberati A, Tetzlaff J, Altman D . Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Int J Surg. 2010; 8(5):336-41. DOI: 10.1016/j.ijsu.2010.02.007. View

13.

. Standards of medical care in diabetes--2014. Diabetes Care. 2013; 37 Suppl 1:S14-80. DOI: 10.2337/dc14-S014. View

14.

Zolk O . Disposition of metformin: variability due to polymorphisms of organic cation transporters. Ann Med. 2011; 44(2):119-29. DOI: 10.3109/07853890.2010.549144. View

15.

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

16.

Nakamura T, Suda T, Kon M . Pathophysiology and treatment of diabetic diarrhea. J Smooth Muscle Res. 1996; 32(2):27-42. DOI: 10.1540/jsmr.32.27. View

17.

Barzilai N, Guo H, Mahoney E, Caporossi S, Golm G, Langdon R . Efficacy and tolerability of sitagliptin monotherapy in elderly patients with type 2 diabetes: a randomized, double-blind, placebo-controlled trial. Curr Med Res Opin. 2011; 27(5):1049-58. DOI: 10.1185/03007995.2011.568059. View

18.

Williams-Herman D, Johnson J, Teng R, Golm G, Kaufman K, Goldstein B . Efficacy and safety of sitagliptin and metformin as initial combination therapy and as monotherapy over 2 years in patients with type 2 diabetes. Diabetes Obes Metab. 2010; 12(5):442-51. DOI: 10.1111/j.1463-1326.2010.01204.x. View

19.

Oh J, Choi M, Kang M, Lee K, Kim J, Kim B . The prevalence of gastrointestinal symptoms in patients with non-insulin dependent diabetes mellitus. Korean J Intern Med. 2009; 24(4):309-17. PMC: 2784973. DOI: 10.3904/kjim.2009.24.4.309. View

20.

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