J Korean Diabetes.  2021 Jun;22(2):91-96. 10.4093/jkd.2021.22.2.91.

Dipeptidyl Peptidase 4 Inhibitor, an Update

Affiliations
  • 1Division of Endocrinology and Metabolism, Department of Internal Medicine, Chungnam National University Hospital, College of Medicine, Chungnam National University, Daejeon, Korea

Abstract

Dipeptidyl peptidase 4 (DPP4) inhibitors, one of the most prescribed second-line antidiabetic drugs in South Korea, have been available since 2006. Many studies focusing on the safety profiles of DPP4 inhibitors have been reported. DPP4 inhibitors were associated with a small increased incidence of acute pancreatitis in placebo-controlled trials, although most observational studies did not support this hypothesis. There were no significant differences in major cardiovascular events in a large prospective cardiovascular outcomes trial with DPP4 inhibitors, although a higher risk of hospitalization for heart failure was reported with saxagliptin. Additionally, the safety data of DPP4 inhibitors for diabetes management during the coronavirus disease-19 (COVID-19) pandemic have been provided recently.

Keyword

COVID-19; Diabetes mellitus; type 2; Dipeptidyl-peptidase IV inhibitors; Heart failure; Pancreatitis

Reference

1. Elrick H, Stimmler L, Hlad CJ Jr, Arai Y. Plasma insulin response to oral and intravenous glucose administration. J Clin Endocrinol Metab. 1964; 24:1076–82.
2. Dupre J, Ross SA, Watson D, Brown JC. Stimulation of insulin secretion by gastric inhibitory polypeptide in man. J Clin Endocrinol Metab. 1973; 37:826–8.
3. Holst JJ, Orskov C, Nielsen OV, Schwartz TW. Truncated glucagon-like peptide I, an insulin-releasing hormone from the distal gut. FEBS Let. 1987; 211:169–74.
Article
4. Flatt PR, Bailey CJ, Green BD. Dipeptidyl peptidase IV (DPP IV) and related molecules in type 2 diabetes. Front Biosci. 2008; 13:3648–60.
Article
5. Butler PC, Elashoff M, Elashoff R, Gale EA. A critical analysis of the clinical use of incretin-based therapies: are the GLP-1 therapies safe? Diabetes Care. 2013; 36:2118–25.
Article
6. Egan AG, Blind E, Dunder K, de Graeff PA, Hummer BT, Bourcier T, et al. Pancreatic safety of incretin-based drugs–FDA and EMA assessment. N Engl J Med. 2014; 370:794–7.
7. Rehman MB, Tudrej BV, Soustre J, Buisson M, Archambault P, Pouchain D, et al. Efficacy and safety of DPP-4 inhibitors in patients with type 2 diabetes: meta-analysis of placebo-controlled randomized clinical trials. Diabetes Metab. 2017; 43:48–58.
Article
8. Singh AK, Gangopadhyay KK, Singh R. Risk of acute pancreatitis with incretin-based therapy: a systematic review and updated meta-analysis of cardiovascular outcomes trials. Expert Rev Clin Pharmacol. 2020; 13:461–8.
Article
9. Azoulay L, Filion KB, Platt RW, Dahl M, Dormuth CR, Clemens KK, et al. Association between incretin-based drugs and the risk of acute pancreatitis. JAMA Intern Med. 2016; 176:1464–73.
Article
10. Dicembrini I, Montereggi C, Nreu B, Mannucci E, Monami M. Pancreatitis and pancreatic cancer in patientes treated with Dipeptidyl Peptidase-4 inhibitors: an extensive and updated meta-analysis of randomized controlled trials. Diabetes Res Clin Pract. 2020; 159:107981.
Article
11. Hiatt WR, Kaul S, Smith RJ. The cardiovascular safety of diabetes drugs–insights from the rosiglitazone experience. N Engl J Med. 2013; 369:1285–7.
12. Scirica BM, Bhatt DL, Braunwald E, Steg PG, Davidson J, Hirshberg B, et al. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med. 2013; 369:1317–26.
Article
13. White WB, Cannon CP, Heller SR, Nissen SE, Bergenstal RM, Bakris GL, et al. Alogliptin after acute coronary syndrome in patients with type 2 diabetes. N Engl J Med. 2013; 369:1327–35.
Article
14. Green JB, Bethel MA, Armstrong PW, Buse JB, Engel SS, Garg J, et al. Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2015; 373:232–42.
Article
15. Rosenstock J, Perkovic V, Johansen OE, Cooper ME, Kahn SE, Marx N, et al. Effect of linagliptin vs placebo on major cardiovascular events in adults with type 2 diabetes and high cardiovascular and renal risk: the CARMELINA randomized clinical trial. JAMA. 2019; 321:69–79.
16. Rosenstock J, Kahn SE, Johansen OE, Zinman B, Espeland MA, Woerle HJ, et al. Effect of linagliptin vs glimepiride on major adverse cardiovascular outcomes in patients with type 2 diabetes: the CAROLINA randomized clinical trial. JAMA. 2019; 322:1155–66.
17. Liu D, Jin B, Chen W, Yun P. Dipeptidyl peptidase 4 (DPP-4) inhibitors and cardiovascular outcomes in patients with type 2 diabetes mellitus (T2DM): a systematic review and meta-analysis. BMC Pharmacol Toxicol. 2019; 20:15.
Article
18. Men P, He N, Song C, Zhai S. Dipeptidyl peptidase-4 inhibitors and risk of arthralgia: a systematic review and meta-analysis. Diabetes Metab. 2017; 43:493–500.
Article
19. Béné J, Moulis G, Bennani I, Auffret M, Coupe P, Babai S, et al. Bullous pemphigoid and dipeptidyl peptidase IV inhibitors: a case-noncase study in the French Pharmacovigilance Database. Br J Dermatol. 2016; 175:296–301.
Article
20. Lee SG, Lee HJ, Yoon MS, Kim DH. Association of dipeptidyl peptidase 4 inhibitor use with risk of bullous pemphigoid in patients with diabetes. JAMA Dermatol. 2019; 155:172–7.
Article
21. Fadini GP, Morieri ML, Longato E, Avogaro A. Prevalence and impact of diabetes among people infected with SARS-CoV-2. J Endocrinol Invest. 2020; 43:867–9.
Article
22. Kim MK, Jeon JH, Kim SW, Moon JS, Cho NH, Han E, et al. The clinical characteristics and outcomes of patients with moderate-to-severe coronavirus disease 2019 infection and diabetes in Daegu, South Korea. Diabetes Metab J. 2020; 44:602–13.
Article
23. Willemen MJ, Mantel-Teeuwisse AK, Straus SM, Meyboom RH, Egberts TC, Leufkens HG. Use of dipeptidyl peptidase-4 inhibitors and the reporting of infections: a disproportionality analysis in the World Health Organization VigiBase. Diabetes Care. 2011; 34:369–74.
Article
24. Gorricho J, Garjón J, Alonso A, Celaya MC, Saiz LC, Erviti J, et al. Use of oral antidiabetic agents and risk of community-acquired pneumonia: a nested case-control study. Br J Clin Pharmacol. 2017; 83:2034–44.
Article
25. Grenet G, Mekhaldi S, Mainbourg S, Auffret M, Cornu C, Cracowski JL, et al. DPP-4 inhibitors and respiratory infection: a systematic review and meta-analysis of the cardiovascular outcomes trials. Diabetes Care. 2021; 44:e36–7.
Article
26. Li W, Moore MJ, Vasilieva N, Sui J, Wong SK, Berne MA, et al. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature. 2003; 426:450–4.
Article
27. Raj VS, Mou H, Smits SL, Dekkers DH, Müller MA, Dijkman R, et al. Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC. Nature. 2013; 495:251–4.
Article
28. Vankadari N, Wilce JA. Emerging WuHan (COVID-19) coronavirus: glycan shield and structure prediction of spike glycoprotein and its interaction with human CD26. Emerg Microbes Infect. 2020; 9:601–4.
29. Li Y, Zhang Z, Yang L, Lian X, Xie Y, Li S, et al. The MERS-CoV receptor DPP4 as a candidate binding target of the SARS-CoV-2 spike. iScience. 2020; 23:101160.
Article
30. Noh Y, Oh IS, Jeong HE, Filion KB, Yu OHY, Shin JY. Association between DPP-4 inhibitors and COVID-19-related outcomes among patients with type 2 diabetes. Diabetes Care. 2021; 44:e64–6.
Article
Full Text Links
  • JKD
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr