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10.01.2021 | Original Article

Dipeptidyl peptidase-4 inhibitors may accelerate cirrhosis decompensation in patients with diabetes and liver cirrhosis: a nationwide population-based cohort study in Taiwan

verfasst von: Fu-Shun Yen, James Cheng-Chung Wei, Hei-Tung Yip, Chii-Min Hwu, Ming-Chih Hou, Chih-Cheng Hsu

Erschienen in: Hepatology International | Ausgabe 1/2021

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Abstract

Background/purpose

Management of type 2 diabetes mellitus (T2DM) in patients with liver cirrhosis is complex and suboptimal, but no clinical trial has adequately investigated antidiabetic drug use for such patients. We evaluate the risk of mortality, cardiovascular events, and hepatic outcomes between dipeptidyl peptidase-4 (DPP-4) inhibitor users and nonusers in patients with type 2 diabetes mellitus (T2DM) and cirrhosis.

Methods

We selected 2828 paired propensity score matched DPP-4 inhibitor users and nonusers from a cohort of T2DM with compensated liver cirrhosis between January 1, 2007, and December 31, 2012. Cox proportional hazards models were used to assess the risk of main outcomes for DPP-4 inhibitor users.

Results

The incidence rate of decompensated cirrhosis during follow-up was 2.20 and 1.53 per 100 patient-years (adjusted hazard ratio [aHR] 1.35, 95% confidence interval [CI] 1.03–1.77) for DPP-4 inhibitor users and nonusers, respectively. The aHRs (95% CI) of variceal bleeding and hepatic failure were 1.67 (1.11–2.52) and 1.35 (1.02–1.79), respectively, for DPP-4 inhibitor users over nonusers. The risk of all-cause mortality, hepatocellular carcinoma, and major cardiovascular events between DPP-4 inhibitor users and nonusers were not statistically different.

Conclusions

This study found that DPP-4 inhibitor users were associated with higher risks of decompensated cirrhosis and hepatic failure than did nonusers among patients with T2DM and compensated liver cirrhosis. We must continue to search for appropriate antidiabetic drugs for patients with liver cirrhosis.
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Literatur
1.
Zurück zum Zitat Elkrief L, Rautou PE, Sarin S, Valla D, Paradis V, Moreau R. Diabetes mellitus in patients with cirrhosis: clinical implications and management. Liver Int. 2016;36:936–48.CrossRef Elkrief L, Rautou PE, Sarin S, Valla D, Paradis V, Moreau R. Diabetes mellitus in patients with cirrhosis: clinical implications and management. Liver Int. 2016;36:936–48.CrossRef
2.
Zurück zum Zitat Mulvihill EE, Drucker DJ. Pharmacology, physiology, and mechanisms of action of dipeptidyl peptidase-4 inhibitors. Endocr Rev. 2014;35:992–1019.CrossRef Mulvihill EE, Drucker DJ. Pharmacology, physiology, and mechanisms of action of dipeptidyl peptidase-4 inhibitors. Endocr Rev. 2014;35:992–1019.CrossRef
3.
Zurück zum Zitat Brunton S. GLP-1 receptor agonists vs. DPP-4 inhibitors for type 2 diabetes: is one approach more successful or preferable than the other? Int J Clin Pract. 2014;68:557–67.CrossRef Brunton S. GLP-1 receptor agonists vs. DPP-4 inhibitors for type 2 diabetes: is one approach more successful or preferable than the other? Int J Clin Pract. 2014;68:557–67.CrossRef
4.
Zurück zum Zitat Iwasaki T, Yoneda M, Inamori M, Shirakawa J, Higurashi T, Maeda S, Terauchi Y, Nakajima A. Sitagliptin as a novel treatment agent for non-alcoholic fatty liver disease patients with type 2 diabetes mellitus. Hepatogastroenterology. 2011;58:2103–5.CrossRef Iwasaki T, Yoneda M, Inamori M, Shirakawa J, Higurashi T, Maeda S, Terauchi Y, Nakajima A. Sitagliptin as a novel treatment agent for non-alcoholic fatty liver disease patients with type 2 diabetes mellitus. Hepatogastroenterology. 2011;58:2103–5.CrossRef
5.
Zurück zum Zitat Yilmaz Y, Yonal O, Deyneli O, Celikel CA, Kalayci C, Duman DG. Effects of sitagliptin in diabetic patients with nonalcoholic steatohepatitis. Acta Gastroenterol Belg. 2012;75:240–4.PubMed Yilmaz Y, Yonal O, Deyneli O, Celikel CA, Kalayci C, Duman DG. Effects of sitagliptin in diabetic patients with nonalcoholic steatohepatitis. Acta Gastroenterol Belg. 2012;75:240–4.PubMed
6.
Zurück zum Zitat Ussher JR, Drucker DJ. Cardiovascular biology of the incretin system. Endocr Rev. 2012;33:187–215.CrossRef Ussher JR, Drucker DJ. Cardiovascular biology of the incretin system. Endocr Rev. 2012;33:187–215.CrossRef
7.
Zurück zum Zitat Ding KH, Zhong Q, Xu J, Isales CM. Glucose-dependent insulinotropic peptide: differential effects on hepatic artery vs portal vein endothelial cells. Am J Physiol Endocrinol Metab. 2004;286:E773–9.CrossRef Ding KH, Zhong Q, Xu J, Isales CM. Glucose-dependent insulinotropic peptide: differential effects on hepatic artery vs portal vein endothelial cells. Am J Physiol Endocrinol Metab. 2004;286:E773–9.CrossRef
8.
Zurück zum Zitat Cheng M. Taiwan’s new national health insurance program: genesis and experience so far. Health Aff (Millwood). 2003;22:61–76.CrossRef Cheng M. Taiwan’s new national health insurance program: genesis and experience so far. Health Aff (Millwood). 2003;22:61–76.CrossRef
9.
Zurück zum Zitat Lin CC, Lai MS, Syu CY, Chang SC, Tseng FY. Accuracy of diabetes diagnosis in health insurance claims data in Taiwan. J Formos Med Assoc. 2005;104:157–63.PubMed Lin CC, Lai MS, Syu CY, Chang SC, Tseng FY. Accuracy of diabetes diagnosis in health insurance claims data in Taiwan. J Formos Med Assoc. 2005;104:157–63.PubMed
10.
Zurück zum Zitat Nehra MS, Ma Y, Clark C, Amarasingham R, Rockey DC, Singal AG. Use of administrative claims data for identifying patients with cirrhosis. J Clin Gastroenterol. 2013;47:e50–4.CrossRef Nehra MS, Ma Y, Clark C, Amarasingham R, Rockey DC, Singal AG. Use of administrative claims data for identifying patients with cirrhosis. J Clin Gastroenterol. 2013;47:e50–4.CrossRef
11.
Zurück zum Zitat Mukerji AN, Patel V, Jain A. Improving survival in decompensated cirrhosis. Int J Hepatol. 2012;2012:318627.CrossRef Mukerji AN, Patel V, Jain A. Improving survival in decompensated cirrhosis. Int J Hepatol. 2012;2012:318627.CrossRef
12.
Zurück zum Zitat Meduru P, Helmer D, Rajan M, Tseng CL, Pogach L, Sambamoorthi U. Chronic illness with complexity: implications for performance measurement of optimal glycemic control. J Gen Intern Med. 2007;22:408–18.CrossRef Meduru P, Helmer D, Rajan M, Tseng CL, Pogach L, Sambamoorthi U. Chronic illness with complexity: implications for performance measurement of optimal glycemic control. J Gen Intern Med. 2007;22:408–18.CrossRef
13.
Zurück zum Zitat Young BA, Lin E, Von Korff M, Simon G, Ciechanowski P, Ludman EJ, Everson-Stewart S, Kinder L, Oliver M, Boyko EJ, et al. Diabetes complications severity index and risk of mortality, hospitalization, and health care utilization. Am J Manag Care. 2008;14:15–23.PubMedPubMedCentral Young BA, Lin E, Von Korff M, Simon G, Ciechanowski P, Ludman EJ, Everson-Stewart S, Kinder L, Oliver M, Boyko EJ, et al. Diabetes complications severity index and risk of mortality, hospitalization, and health care utilization. Am J Manag Care. 2008;14:15–23.PubMedPubMedCentral
14.
Zurück zum Zitat Wang X, Sarin SK, Ning Q. Definition of ACLF and inclusion criteria for extra-hepatic organ failure. Hepatol Int. 2015;9(3):360–5.CrossRef Wang X, Sarin SK, Ning Q. Definition of ACLF and inclusion criteria for extra-hepatic organ failure. Hepatol Int. 2015;9(3):360–5.CrossRef
15.
Zurück zum Zitat D’Agostino RB Jr. Propensity score methods for bias reduction in the comparison of a treatment to a non-randomized control group. Stat Med. 1998;17:2265–81.CrossRef D’Agostino RB Jr. Propensity score methods for bias reduction in the comparison of a treatment to a non-randomized control group. Stat Med. 1998;17:2265–81.CrossRef
16.
Zurück zum Zitat Iezzoni LI. Risk adjustment for measuring healthcare outcomes. Chicago: Health Administration Press; 1997. Iezzoni LI. Risk adjustment for measuring healthcare outcomes. Chicago: Health Administration Press; 1997.
17.
Zurück zum Zitat GBD 2017 Causes of Death Collaborators. Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980–2017: a systematic analysis for the global burden of disease study 2017. Lancet 2018;392:1736–1788 GBD 2017 Causes of Death Collaborators. Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980–2017: a systematic analysis for the global burden of disease study 2017. Lancet 2018;392:1736–1788
18.
Zurück zum Zitat Fleming KM, Aithal GP, Card TR, West J. All-cause mortality in people with cirrhosis compared with the general population: a population-based cohort study. Liver Int. 2012;32:79–84.CrossRef Fleming KM, Aithal GP, Card TR, West J. All-cause mortality in people with cirrhosis compared with the general population: a population-based cohort study. Liver Int. 2012;32:79–84.CrossRef
19.
Zurück zum Zitat Scheen AJ. Cardiovascular effects of new oral glucose-lowering agents: DPP-4 and SGLT-2 inhibitors. Circ Res. 2018;122:1439–59.CrossRef Scheen AJ. Cardiovascular effects of new oral glucose-lowering agents: DPP-4 and SGLT-2 inhibitors. Circ Res. 2018;122:1439–59.CrossRef
20.
Zurück zum Zitat Armstrong MJ, Gaunt P, Aithal GP, et al. Liraglutide safety and efficacy in patients with non-alcoholic steatohepatitis (LEAN): a multicentre, double-blind, randomised, placebo-controlled phase 2 study. Lancet. 2016;387:679–90.CrossRef Armstrong MJ, Gaunt P, Aithal GP, et al. Liraglutide safety and efficacy in patients with non-alcoholic steatohepatitis (LEAN): a multicentre, double-blind, randomised, placebo-controlled phase 2 study. Lancet. 2016;387:679–90.CrossRef
21.
Zurück zum Zitat Gouverneur A, Lair A, Arnaud M, Begaud B, Raschi E, Pariente A, Salvo F. DPP-4 inhibitors and venous thromboembolism: an analysis of the WHO spontaneous reporting database. Lancet Diabetes Endocrinol. 2020;8:365–7.CrossRef Gouverneur A, Lair A, Arnaud M, Begaud B, Raschi E, Pariente A, Salvo F. DPP-4 inhibitors and venous thromboembolism: an analysis of the WHO spontaneous reporting database. Lancet Diabetes Endocrinol. 2020;8:365–7.CrossRef
22.
Zurück zum Zitat Gupta AK, Verma AK, Kailashiya J, Singh SK, Kumar N. Sitagliptin: anti-platelet effect in diabetes and healthy volunteers. Platelets. 2012;23:565–70.CrossRef Gupta AK, Verma AK, Kailashiya J, Singh SK, Kumar N. Sitagliptin: anti-platelet effect in diabetes and healthy volunteers. Platelets. 2012;23:565–70.CrossRef
23.
Zurück zum Zitat Ligueros-Saylan M, Foley JE, Schweizer A, Couturier A, Kothny W. An assessment of adverse effects of vildagliptin versus comparators on the liver, the pancreas, the immune system, the skin and in patients with impaired renal function from a large pooled database of Phase II and III clinical trials. Diabetes Obes Metab. 2010;12:495–509.CrossRef Ligueros-Saylan M, Foley JE, Schweizer A, Couturier A, Kothny W. An assessment of adverse effects of vildagliptin versus comparators on the liver, the pancreas, the immune system, the skin and in patients with impaired renal function from a large pooled database of Phase II and III clinical trials. Diabetes Obes Metab. 2010;12:495–509.CrossRef
24.
Zurück zum Zitat Asakawa M, Mitsui H, Akihisa M, Sekine T, Niitsu Y, Kobayashi A, Hashimoto N, Kawamura M, Ogawa Y. Efficacy and safety of sitagliptin for the treatment of diabetes mellitus complicated by chronic liver injury. Springerplus. 2015;4:346.CrossRef Asakawa M, Mitsui H, Akihisa M, Sekine T, Niitsu Y, Kobayashi A, Hashimoto N, Kawamura M, Ogawa Y. Efficacy and safety of sitagliptin for the treatment of diabetes mellitus complicated by chronic liver injury. Springerplus. 2015;4:346.CrossRef
25.
Zurück zum Zitat Langer DA, Shah VH. Nitric oxide and portal hypertension: interface of vasoreactivity and angiogenesis. J Hepatol. 2006;44:209–16.CrossRef Langer DA, Shah VH. Nitric oxide and portal hypertension: interface of vasoreactivity and angiogenesis. J Hepatol. 2006;44:209–16.CrossRef
26.
Zurück zum Zitat Monami M, Dicembrini I, Martelli D, Mannucci E. Safety of dipeptidyl peptidase-4 inhibitors: a meta-analysis of randomized clinical trials. Curr Med Res Opin. 2011;27:57–64.CrossRef Monami M, Dicembrini I, Martelli D, Mannucci E. Safety of dipeptidyl peptidase-4 inhibitors: a meta-analysis of randomized clinical trials. Curr Med Res Opin. 2011;27:57–64.CrossRef
27.
Zurück zum Zitat Itou M, Kawaguchi T, Taniguchi E, Sata M. Dipeptidyl peptidase-4: a key player in chronic liver disease. World J Gastroenterol. 2013;19:2298–306.CrossRef Itou M, Kawaguchi T, Taniguchi E, Sata M. Dipeptidyl peptidase-4: a key player in chronic liver disease. World J Gastroenterol. 2013;19:2298–306.CrossRef
28.
Zurück zum Zitat Yamamoto S, Tokuhara T, Nishikawa M, Nishizawa S, Nishioka T, Nozawa A, Takahashi A, Watanabe Y, Wada R, Wakasa K, et al. Spontaneous regression of hepatocellular carcinoma after improving diabetes mellitus: possibly responsible for immune system. Kanzo. 2012;53:164–7.CrossRef Yamamoto S, Tokuhara T, Nishikawa M, Nishizawa S, Nishioka T, Nozawa A, Takahashi A, Watanabe Y, Wada R, Wakasa K, et al. Spontaneous regression of hepatocellular carcinoma after improving diabetes mellitus: possibly responsible for immune system. Kanzo. 2012;53:164–7.CrossRef
29.
Zurück zum Zitat Gundling F, Seidl H, Strassen I, Haller B, Siegmund T, Umgelter A, Pehl C, Schepp W, Schumm-Draeger PM. Clinical manifestations and treatment options in patients with cirrhosis and diabetes mellitus. Digestion. 2013;87:75–84.CrossRef Gundling F, Seidl H, Strassen I, Haller B, Siegmund T, Umgelter A, Pehl C, Schepp W, Schumm-Draeger PM. Clinical manifestations and treatment options in patients with cirrhosis and diabetes mellitus. Digestion. 2013;87:75–84.CrossRef
30.
Zurück zum Zitat Harrison MF. The misunderstood coagulopathy of liver disease: a review for the acute setting. West J Emerg Med. 2018;19:863–71.CrossRef Harrison MF. The misunderstood coagulopathy of liver disease: a review for the acute setting. West J Emerg Med. 2018;19:863–71.CrossRef
Metadaten
Titel
Dipeptidyl peptidase-4 inhibitors may accelerate cirrhosis decompensation in patients with diabetes and liver cirrhosis: a nationwide population-based cohort study in Taiwan
verfasst von
Fu-Shun Yen
James Cheng-Chung Wei
Hei-Tung Yip
Chii-Min Hwu
Ming-Chih Hou
Chih-Cheng Hsu
Publikationsdatum
10.01.2021
Verlag
Springer India
Erschienen in
Hepatology International / Ausgabe 1/2021
Print ISSN: 1936-0533
Elektronische ISSN: 1936-0541
DOI
https://doi.org/10.1007/s12072-020-10122-1

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