| GLP-1 RA and Reduced Liver and Non-Liver Complications in Adults with T2D and MASLD: A Target Trial Emulation Study |
| Xianhua Mao1,2, Xinrong Zhang1, Rongtao Lai1,3, Ka-Shing Cheung2, Man-Fung Yuen2,4, Ramsey Cheung1,5, Wai-Kay Seto2,4,6, Mindie H Nguyen1,7 |
1Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California
2Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong
3Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
4State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong
5Division of Gastroenterology and Hepatology, Veterans Affairs Palo Alto Healthcare System, Palo Alto, California
6Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
7Department of Epidemiology and Population Health, Stanford University Medical Center, Palo Alto, California |
|
|
|
Received: December 5, 2024 Revised: February 26, 2025 Accepted: April 21, 2025 |
|
|
| ABSTRACT |
|
Background/aims
Information about the association of glucagon-like peptidase 1 receptor agonist (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 (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 1000 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. |
| KeyWords:
CVD, MASLD, NAFLD, fatty liver, GLP, tumor, renal disease, liver cancer, non-liver cancer |
|
|
PDF Links
Full text via DOI
Download Citation
