Glucagon-like peptide 1 receptor agonist and reduced liver and non-liver complications in adults with type 2 diabetes and metabolic dysfunction-associated steatotic liver disease: a target trial emulation study
Background/Aims Information about the association of glucagon-like peptide-1 receptor (GLP-1RA) with liver and non-liver complications is insufficient in patients with type 2 diabetes (T2D) and metabolic dysfunction-associated steatotic liver disease (MASLD). We conducted a target trial emulation st...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Korean Association for the Study of the Liver
2025-07-01
|
| Series: | Clinical and Molecular Hepatology |
| Subjects: | |
| Online Access: | http://e-cmh.org/upload/pdf/cmh-2024-1096.pdf |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849703007274401792 |
|---|---|
| author | Xianhua Mao Xinrong Zhang Rongtao Lai Ka-Shing Cheung Man-Fung Yuen Ramsey Cheung Wai-Kay Seto Mindie H. Nguyen |
| author_facet | Xianhua Mao Xinrong Zhang Rongtao Lai Ka-Shing Cheung Man-Fung Yuen Ramsey Cheung Wai-Kay Seto Mindie H. Nguyen |
| author_sort | Xianhua Mao |
| collection | DOAJ |
| description | Background/Aims Information about the association of glucagon-like peptide-1 receptor (GLP-1RA) with liver and non-liver complications is insufficient in patients with type 2 diabetes (T2D) and metabolic dysfunction-associated steatotic liver disease (MASLD). We conducted a target trial emulation study to evaluate whether GLP-1RA decreases the risk of liver and non-liver outcomes. Methods Patients with T2D and MASLD initiating GLP-1RA or dipeptidyl peptidase-4 inhibitor (DPP-4i) were included from 2013 to 2022 in Merative™ Marketscan® Research Databases. Primary outcomes included incidences of (1) hepatocellular carcinoma (HCC) and cirrhosis, and (2) cardiovascular disease (CVD), chronic kidney disease (CKD), and non-liver cancer. Inverse probability of treatment weighting was applied to balance baseline characteristics and Cox regression models were conducted to estimate hazard ratio (HR) and 95% confidence interval (CI). Results In the intention-to-treat design, GLP-1RA, compared with DPP-4i, had a significantly lower incidence (per 1,000 person-years) of HCC (0.8 vs. 1.7; HR 0.53, 95% CI 0.39–0.71), of cirrhosis (29.3 vs. 32.9; HR 0.91, 95% CI 0.86–0.96), of CVD (57.2 vs. 73.9; HR 0.90, 95% CI 0.86–0.95), of CKD (4.5 vs. 6.8; HR 0.73, 95% CI 0.64–0.84), and of non-liver cancer (16.9 vs. 22.9; HR 0.82, 95% CI 0.77–0.89). In the per-protocol design, significant inverse associations for these study outcomes still were observed, with HR 0.60–0.77. Conclusions In this emulated target trial of nationwide patients with T2D and MASLD, GLP-1RA use, when compared with DPP-4i, was associated with a significantly lower risk of liver and non-liver complications. |
| format | Article |
| id | doaj-art-2889c7c7bc784c319635d35d44bcb1ee |
| institution | DOAJ |
| issn | 2287-2728 2287-285X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Korean Association for the Study of the Liver |
| record_format | Article |
| series | Clinical and Molecular Hepatology |
| spelling | doaj-art-2889c7c7bc784c319635d35d44bcb1ee2025-08-20T03:17:26ZengKorean Association for the Study of the LiverClinical and Molecular Hepatology2287-27282287-285X2025-07-013131084109910.3350/cmh.2024.10962241Glucagon-like peptide 1 receptor agonist and reduced liver and non-liver complications in adults with type 2 diabetes and metabolic dysfunction-associated steatotic liver disease: a target trial emulation studyXianhua Mao0Xinrong Zhang1Rongtao Lai2Ka-Shing Cheung3Man-Fung Yuen4Ramsey Cheung5Wai-Kay Seto6Mindie H. Nguyen7 Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USABackground/Aims Information about the association of glucagon-like peptide-1 receptor (GLP-1RA) with liver and non-liver complications is insufficient in patients with type 2 diabetes (T2D) and metabolic dysfunction-associated steatotic liver disease (MASLD). We conducted a target trial emulation study to evaluate whether GLP-1RA decreases the risk of liver and non-liver outcomes. Methods Patients with T2D and MASLD initiating GLP-1RA or dipeptidyl peptidase-4 inhibitor (DPP-4i) were included from 2013 to 2022 in Merative™ Marketscan® Research Databases. Primary outcomes included incidences of (1) hepatocellular carcinoma (HCC) and cirrhosis, and (2) cardiovascular disease (CVD), chronic kidney disease (CKD), and non-liver cancer. Inverse probability of treatment weighting was applied to balance baseline characteristics and Cox regression models were conducted to estimate hazard ratio (HR) and 95% confidence interval (CI). Results In the intention-to-treat design, GLP-1RA, compared with DPP-4i, had a significantly lower incidence (per 1,000 person-years) of HCC (0.8 vs. 1.7; HR 0.53, 95% CI 0.39–0.71), of cirrhosis (29.3 vs. 32.9; HR 0.91, 95% CI 0.86–0.96), of CVD (57.2 vs. 73.9; HR 0.90, 95% CI 0.86–0.95), of CKD (4.5 vs. 6.8; HR 0.73, 95% CI 0.64–0.84), and of non-liver cancer (16.9 vs. 22.9; HR 0.82, 95% CI 0.77–0.89). In the per-protocol design, significant inverse associations for these study outcomes still were observed, with HR 0.60–0.77. Conclusions In this emulated target trial of nationwide patients with T2D and MASLD, GLP-1RA use, when compared with DPP-4i, was associated with a significantly lower risk of liver and non-liver complications.http://e-cmh.org/upload/pdf/cmh-2024-1096.pdfcardiovascular diseasemetabolic dysfunction-associated steatotic liver diseasenon-alcoholic fatty liver diseasefatty liverliver cancer |
| spellingShingle | Xianhua Mao Xinrong Zhang Rongtao Lai Ka-Shing Cheung Man-Fung Yuen Ramsey Cheung Wai-Kay Seto Mindie H. Nguyen Glucagon-like peptide 1 receptor agonist and reduced liver and non-liver complications in adults with type 2 diabetes and metabolic dysfunction-associated steatotic liver disease: a target trial emulation study Clinical and Molecular Hepatology cardiovascular disease metabolic dysfunction-associated steatotic liver disease non-alcoholic fatty liver disease fatty liver liver cancer |
| title | Glucagon-like peptide 1 receptor agonist and reduced liver and non-liver complications in adults with type 2 diabetes and metabolic dysfunction-associated steatotic liver disease: a target trial emulation study |
| title_full | Glucagon-like peptide 1 receptor agonist and reduced liver and non-liver complications in adults with type 2 diabetes and metabolic dysfunction-associated steatotic liver disease: a target trial emulation study |
| title_fullStr | Glucagon-like peptide 1 receptor agonist and reduced liver and non-liver complications in adults with type 2 diabetes and metabolic dysfunction-associated steatotic liver disease: a target trial emulation study |
| title_full_unstemmed | Glucagon-like peptide 1 receptor agonist and reduced liver and non-liver complications in adults with type 2 diabetes and metabolic dysfunction-associated steatotic liver disease: a target trial emulation study |
| title_short | Glucagon-like peptide 1 receptor agonist and reduced liver and non-liver complications in adults with type 2 diabetes and metabolic dysfunction-associated steatotic liver disease: a target trial emulation study |
| title_sort | glucagon like peptide 1 receptor agonist and reduced liver and non liver complications in adults with type 2 diabetes and metabolic dysfunction associated steatotic liver disease a target trial emulation study |
| topic | cardiovascular disease metabolic dysfunction-associated steatotic liver disease non-alcoholic fatty liver disease fatty liver liver cancer |
| url | http://e-cmh.org/upload/pdf/cmh-2024-1096.pdf |
| work_keys_str_mv | AT xianhuamao glucagonlikepeptide1receptoragonistandreducedliverandnonlivercomplicationsinadultswithtype2diabetesandmetabolicdysfunctionassociatedsteatoticliverdiseaseatargettrialemulationstudy AT xinrongzhang glucagonlikepeptide1receptoragonistandreducedliverandnonlivercomplicationsinadultswithtype2diabetesandmetabolicdysfunctionassociatedsteatoticliverdiseaseatargettrialemulationstudy AT rongtaolai glucagonlikepeptide1receptoragonistandreducedliverandnonlivercomplicationsinadultswithtype2diabetesandmetabolicdysfunctionassociatedsteatoticliverdiseaseatargettrialemulationstudy AT kashingcheung glucagonlikepeptide1receptoragonistandreducedliverandnonlivercomplicationsinadultswithtype2diabetesandmetabolicdysfunctionassociatedsteatoticliverdiseaseatargettrialemulationstudy AT manfungyuen glucagonlikepeptide1receptoragonistandreducedliverandnonlivercomplicationsinadultswithtype2diabetesandmetabolicdysfunctionassociatedsteatoticliverdiseaseatargettrialemulationstudy AT ramseycheung glucagonlikepeptide1receptoragonistandreducedliverandnonlivercomplicationsinadultswithtype2diabetesandmetabolicdysfunctionassociatedsteatoticliverdiseaseatargettrialemulationstudy AT waikayseto glucagonlikepeptide1receptoragonistandreducedliverandnonlivercomplicationsinadultswithtype2diabetesandmetabolicdysfunctionassociatedsteatoticliverdiseaseatargettrialemulationstudy AT mindiehnguyen glucagonlikepeptide1receptoragonistandreducedliverandnonlivercomplicationsinadultswithtype2diabetesandmetabolicdysfunctionassociatedsteatoticliverdiseaseatargettrialemulationstudy |