Skip to main content

Advertisement

Log in

Association between therapy with dipeptidyl peptidase-4 (DPP-4) inhibitors and risk of ileus: a cohort study

Diabetology International Aims and scope Submit manuscript

Abstract

Background

Three cases of ileus have been published among dipeptidyl peptidase-4 (DPP-4) inhibitor users in Japan. The purpose of this study was to estimate and compare incidence rates of ileus among alogliptin users and users of other DPP-4 inhibitors, glucagon-like peptide 1 (GLP-1) receptor agonists, and voglibose.

Methods

We used the Medical Data Vision database in Japan to conduct a retrospective cohort study among type 2 diabetes mellitus (T2DM) patients who were new users of alogliptin, other DPP-4 inhibitors, GLP-1 receptor agonists, or voglibose between 1 April 2010 and 30 April 2014. The primary outcome was an incident diagnosis of ileus. Kaplan–Meier survival curves were used to estimate ileus events over time. Adjusted Poisson regression models were used to estimate incidence rate ratios (IRR) for ileus and 95 % confidence intervals (CI) by comparing alogliptin users to users of the other study drugs.

Results

We identified 82,386 patients with T2DM. In the adjusted model, there was no difference in risk of ileus among patients exposed to alogliptin compared with patients exposed to other DPP-4 inhibitors (IRR 1.15, 95 % CI 0.75–1.75) or GLP-1 receptor agonists (IRR 0.42, 95 % CI 0.14–1.20). The risk of ileus was significantly lower among patients exposed to alogliptin compared with patients exposed to voglibose (IRR 0.55, 95 % CI 0.35–0.88).

Conclusions

The independent risk of ileus among new users of alogliptin did not significantly differ compared with new users of other DPP-4 inhibitors or GLP-1 receptor agonists but was significantly lower than new users of voglibose.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Srinivasan BT, Jarvis J, Khunti K, Davies MJ. Recent advances in the management of type 2 diabetes mellitus: a review. Postgrad Med J. 2008;84:524–31.

    Article  CAS  PubMed  Google Scholar 

  2. Richard KR, Shelburne JS, Kirk JK. Tolerability of dipeptidyl peptidase-4 inhibitors: a review. Clin Ther. 2011;33:1609–29.

    Article  CAS  PubMed  Google Scholar 

  3. DeFronzo RA, Fleck PR, Wilson CA, Mekki Q, Alogliptin Study Group. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor alogliptin in patients with type 2 diabetes and inadequate glycemic control: a randomized, double-blind, placebo-controlled study. Diabetes Care. 2008;31:2315–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Kanasaki K, Konishi K, Hayashi R, Shiroeda H, Nomura T, Nakagawa A, Nagai T, Takeda-Watanabe A, Ito H, Tsuda S, Kitada M, Fujii M, Kanasaki M, Nishizawa M, Nakano Y, Tomita Y, Ueda N, Kosaka T, Koya D. Three ileus cases associated with the use of dipeptidyl peptidase-4 inhibitors in diabetic patients. J Diabetes Investig. 2013;4:673–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Holte K, Kehlet H. Postoperative ileus: a preventable event. Br J Surg. 2000;87:1480–93.

    Article  CAS  PubMed  Google Scholar 

  6. Hayanga AJ, Bass-Wilkins K, Bulkley GB. Current management of small-bowel obstruction. Adv Surg. 2005;39:1–33.

    Article  PubMed  Google Scholar 

  7. Hayden GE, Sprouse KL. Bowel obstruction and hernia. Emerg Med Clin North Am. 2011;29:319–45.

    Article  PubMed  Google Scholar 

  8. Nielsen J, Meyer JM. Risk factors for ileus in patients with schizophrenia. Schizophr Bull. 2012;38:592–8.

    Article  PubMed  Google Scholar 

  9. Marathe CS, Rayner CK, Jones KL, Horowitz M. Effects of GLP-1 and incretin-based therapies on gastrointestinal motor function. Exp Diabetes Res. 2011;2011:279530.

    Article  PubMed  PubMed Central  Google Scholar 

  10. DeFronzo RA, Okerson T, Viswanathan P, Guan X, Holcombe JH, MacConell L. Effects of exenatide versus sitagliptin on postprandial glucose, insulin and glucagon secretion, gastric emptying, and caloric intake: a randomized, cross-over study. Curr Med Res Opin. 2008;24:2943–52.

    Article  CAS  PubMed  Google Scholar 

  11. Vella A, Bock G, Giesler PD, Burton DB, Serra DB, Saylan ML, Deacon CF, Foley JE, Rizza RA, Camilleri M. The effect of dipeptidyl peptidase-4 inhibition on gastric volume, satiation and enteroendocrine secretion in type 2 diabetes: a double-blind, placebo-controlled crossover study. Clin Endocrinol Oxf. 2008;69:737–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Vella A, Bock G, Giesler PD, Burton DB, Serra DB, Saylan ML, Dunning BE, Foley JE, Rizza RA, Camilleri M. Effects of dipeptidyl peptidase-4 inhibition on gastrointestinal function, meal appearance, and glucose metabolism in type 2 diabetes. Diabetes. 2007;56:1475–80.

    Article  CAS  PubMed  Google Scholar 

  13. Azami Y. Paralytic ileus accompanied by pneumatosis cystoides intestinalis after acarbose treatment in an elderly diabetic patient with a history of heavy intake of maltitol. Intern Med. 2000;39:826–9.

    Article  CAS  PubMed  Google Scholar 

  14. Iwamoto Y, Kashiwagi A, Yamada N, Terao S, Mimori N, Suzuki M, Tachibana H. Efficacy and safety of vildagliptin and voglibose in Japanese patients with type 2 diabetes: a 12-week, randomized, double-blind, active-controlled study. Diabetes Obes Metab. 2010;12:700–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Nishii Y, Aizawa T, Hashizume K. Ileus: a rare side effect of acarbose. Diabetes Care. 1996;19:1033.

    Article  CAS  PubMed  Google Scholar 

  16. Oba K, Suzuki K, Ouchi M, Matsumura N, Suzuki T, Nakano H. Repeated episodes of paralytic ileus in an elderly diabetic patient treated with voglibose. J Am Geriatr Soc. 2006;54:182–3.

    Article  PubMed  Google Scholar 

  17. Urushihara H, Taketsuna M, Liu Y, Oda E, Nakamura M, et al. Increased risk of acute pancreatitis in patients with type 2 diabetes: an observational study using a Japanese hospital database. PLoS One. 2012;7(12):e53224. doi:10.1371/journal.pone.0053224.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. De Hert M, Hudyana H, Dockx L, Bernagie C, Sweers K, Tack J, Leucht S, Peuskens J. Second-generation antipsychotics and constipation: a review of the literature. Eur Psychiatry. 2011;26:34–44.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The authors thank Dr. Neila N. Smith for her advice during the study and thoughtful review and comments on our manuscript. The authors also thank Elizabeth Suarez for editorial assistance in preparing this manuscript.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Dimitri Bennett.

Ethics declarations

Conflict of interest

All authors declare that they have no conflict of interest except that they are all employees of Takeda Pharmaceutical Company Limited.

Ethics policy

This article does not contain any studies with human or animal subjects performed by any of the authors.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bennett, D., Davé, S., Sakaguchi, M. et al. Association between therapy with dipeptidyl peptidase-4 (DPP-4) inhibitors and risk of ileus: a cohort study. Diabetol Int 7, 375–383 (2016). https://doi.org/10.1007/s13340-016-0261-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13340-016-0261-3

Keywords

Navigation