Beneficial Effect of Omarigliptin on Diabetic Patients with Non-alcoholic Fatty Liver Disease/non-alcoholic Steatohepatitis

Overview

Journal Diabetol Metab Syndr

Publisher Biomed Central

Specialty Endocrinology

Date 2021 Mar 11

PMID 33691757

Citations 7

Authors

Sachiko Hattori

Kazuomi Nomoto

Tomohiko Suzuki

Seishu Hayashi

Affiliations

Soon will be listed here.

Abstract

Background: Dipeptidyl peptidase 4 (DPP4) is a serine exopeptidase able to inactivate various oligopeptides, and also a hepatokine. Hepatocyte-specific overexpression of DPP4 is associated with hepatic insulin resistance and liver steatosis.

Method: We examined whether weekly DPP4 inhibitor omarigliptin (OMG) can improve liver function as well as levels of inflammation and insulin resistance in type 2 diabetic patients with non-alcoholic fatty liver disease (NAFLD). Further, we investigated the effects of OMG in a diabetic patient with biopsy-confirmed nonalcoholic steatohepatitis (NASH).

Results: In NAFLD patients, OMG significantly decreased levels of aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, homeostatic model assessment of insulin resistance (HOMA-IR), and high-sensitivity C-reactive protein (hsCRP), while no significant change was seen in hemoglobin A1c or body mass index. In the NASH patient, liver function improved markedly, and levels of the hepatic fibrosis marker FIB-4 decreased in parallel with HOMA-IR and hsCRP. Slight but clear improvements in intrahepatic fat deposition and fibrosis appeared to be seen on diagnostic ultrasonography.

Conclusion: Weekly administration of the DPP4 inhibitor OMG in ameliorating hepatic insulin resistance may cause beneficial effects in liver with NAFLD/NASH.

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References

Varin E, Mulvihill E, Beaudry J, Pujadas G, Fuchs S, Tanti J . Circulating Levels of Soluble Dipeptidyl Peptidase-4 Are Dissociated from Inflammation and Induced by Enzymatic DPP4 Inhibition. Cell Metab. 2018; 29(2):320-334.e5. DOI: 10.1016/j.cmet.2018.10.001. View

Silva Junior W, Souza M, Nogueira Neto J, Bouskela E, Kraemer-Aguiar L . Dipeptidyl Peptidase 4 Activity Is Related to Body Composition, Measures of Adiposity, and Insulin Resistance in Subjects with Excessive Adiposity and Different Degrees of Glucose Tolerance. J Diabetes Res. 2019; 2019:5238013. PMC: 6388345. DOI: 10.1155/2019/5238013. View

Kloting N, Fasshauer M, Dietrich A, Kovacs P, Schon M, Kern M . Insulin-sensitive obesity. Am J Physiol Endocrinol Metab. 2010; 299(3):E506-15. DOI: 10.1152/ajpendo.00586.2009. View

Hattori S . Omarigliptin decreases inflammation and insulin resistance in a pleiotropic manner in patients with type 2 diabetes. Diabetol Metab Syndr. 2020; 12:24. PMC: 7092436. DOI: 10.1186/s13098-020-00533-3. View

Ghorpade D, Ozcan L, Zheng Z, Nicoloro S, Shen Y, Chen E . Hepatocyte-secreted DPP4 in obesity promotes adipose inflammation and insulin resistance. Nature. 2018; 555(7698):673-677. PMC: 6021131. DOI: 10.1038/nature26138. View

Dong Y, Lv Q, Li S, Wu Y, Li L, Li J . Efficacy and safety of glucagon-like peptide-1 receptor agonists in non-alcoholic fatty liver disease: A systematic review and meta-analysis. Clin Res Hepatol Gastroenterol. 2017; 41(3):284-295. DOI: 10.1016/j.clinre.2016.11.009. View

Akuta N, Watanabe C, Kawamura Y, Arase Y, Saitoh S, Fujiyama S . Effects of a sodium-glucose cotransporter 2 inhibitor in nonalcoholic fatty liver disease complicated by diabetes mellitus: Preliminary prospective study based on serial liver biopsies. Hepatol Commun. 2018; 1(1):46-52. PMC: 5747031. DOI: 10.1002/hep4.1019. View

Baumeier C, Schluter L, Saussenthaler S, Laeger T, Rodiger M, Alaze S . Elevated hepatic DPP4 activity promotes insulin resistance and non-alcoholic fatty liver disease. Mol Metab. 2017; 6(10):1254-1263. PMC: 5641684. DOI: 10.1016/j.molmet.2017.07.016. View

Sterling R, Lissen E, Clumeck N, Sola R, Correa M, Montaner J . Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology. 2006; 43(6):1317-25. DOI: 10.1002/hep.21178. View

10.

Lamers D, Famulla S, Wronkowitz N, Hartwig S, Lehr S, Ouwens D . Dipeptidyl peptidase 4 is a novel adipokine potentially linking obesity to the metabolic syndrome. Diabetes. 2011; 60(7):1917-25. PMC: 3121429. DOI: 10.2337/db10-1707. View

11.

Younossi Z, Koenig A, Abdelatif D, Fazel Y, Henry L, Wymer M . Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2015; 64(1):73-84. DOI: 10.1002/hep.28431. View

12.

Rufinatscha K, Radlinger B, Dobner J, Folie S, Bon C, Profanter E . Dipeptidyl peptidase-4 impairs insulin signaling and promotes lipid accumulation in hepatocytes. Biochem Biophys Res Commun. 2017; 485(2):366-371. DOI: 10.1016/j.bbrc.2017.02.071. View

13.

Rohrborn D, Bruckner J, Sell H, Eckel J . Reduced DPP4 activity improves insulin signaling in primary human adipocytes. Biochem Biophys Res Commun. 2016; 471(3):348-54. DOI: 10.1016/j.bbrc.2016.02.019. View

14.

Silva Junior W, Souza M, Kraemer-Aguiar L . Dipeptidyl peptidase 4 (DPP4), adipose inflammation, and insulin resistance: is it time to look to the hepatocyte?. Hepatobiliary Surg Nutr. 2019; 7(6):499-500. PMC: 6295385. DOI: 10.21037/hbsn.2018.10.05. View

15.

Godoy-Matos A, Silva Junior W, Valerio C . NAFLD as a continuum: from obesity to metabolic syndrome and diabetes. Diabetol Metab Syndr. 2020; 12:60. PMC: 7359287. DOI: 10.1186/s13098-020-00570-y. View