A retrospective analysis of combination therapy with GLP-1 receptor agonists and SGLT2 inhibitors versus SGLT2 inhibitor monotherapy in patients with MASLD

Jheng-Yan Wu, Wan-Hsuan Hsu, Chia-Chih Kuo, Ya-Wen Tsai, Ting-Hui Liu, Po-Yu Huang, Min-Hsiang Chuang, Kuo-Chuan Hung, Tsung Yu and Chih-Cheng Lai ()
Additional contact information
Jheng-Yan Wu: Chi Mei Medical Center
Wan-Hsuan Hsu: Chi Mei Medical Center
Chia-Chih Kuo: Chi Mei Medical Center
Ya-Wen Tsai: Chi Mei Medical Center
Ting-Hui Liu: Chi Mei Medical Center
Po-Yu Huang: Chi Mei Medical Center
Min-Hsiang Chuang: Chi Mei Medical Center
Kuo-Chuan Hung: Chi Mei Medical Center
Tsung Yu: National Cheng Kung University
Chih-Cheng Lai: Chi Mei Medical Center

Nature Communications, 2025, vol. 16, issue 1, 1-10

Abstract: Abstract The impact of adding glucagon-like peptide-1 receptor agonists (GLP-1RAs) to sodium-glucose co-transporter-2 inhibitors (SGLT2is) for metabolic dysfunction-associated steatotic liver disease (MASLD) is unclear. This retrospective study compared the effect of GLP-1RA plus SGLT2i versus SGLT2i alone for MASLD. Combination therapy was associated with a lower risk of primary composite outcomes of all-cause hospitalization, all-cause mortality, major adverse cardiovascular events (MACE), major adverse kidney events (MAKE), and major adverse liver outcomes (MALO) (hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.84-0.91). Combination therapy also showed lower risks for all-cause hospitalization (HR, 0.86; 95% CI, 0.82-0.90), all-cause mortality (HR, 0.45; 95% CI, 0.38-0.53), MAKE (HR, 0.72; 95% CI, 0.60-0.89), and MALO (HR, 0.61; 95% CI, 0.53-0.69). In contrast, compared to GLP-1RA monotherapy, combination therapy did not confer additional benefit except for all-cause mortality. Overall, combination therapy with GLP-1RA plus SGLT2i was associated with better clinical outcomes of MASLD, compared to SGLT2i monotherapy.

Date: 2025
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DOI: 10.1038/s41467-025-62891-8

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