BACKGROUND AIMS: Glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose cotransporter-2 (SGLT-2) inhibitors individually benefit patients with metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to evaluate the effect of GLP-1 receptor agonist-SGLT-2 inhibitor combination on the risk of major adverse liver and cardiovascular outcomes compared with either agent alone among patients with MASLD and type 2 diabetes (T2D).
METHODS: This is a target trial emulation study using data from U.S. Marketscan Databases. Propensity score-matched cohorts were built to compare (1) 4606 patients who received GLP-1 receptor agonist-SGLT-2 inhibitor combination with 18424 who received only GLP-1 receptor agonist, and (2) 5368 patients who received this combination with 21472 who received only SGLT-2 inhibitor. Cox regression models were conducted in on-treatment designs.
RESULTS: Compared with GLP-1 receptor agonists, GLP-1 receptor agonist-SGLT-2 inhibitor combination was associated with a 39% lower risk of major adverse liver outcomes (HR 0.61 [95%CI 0.49 to 0.77]) and a 35% lower risk of major adverse cardiovascular events (HR 0.65 [0.60 to 0.70]) during a median follow-up of 6.3 months. Compared with SGLT-2 inhibitors, the combination was associated with a 43% lower risk of major adverse liver outcomes (HR 0.57 [0.46 to 0.69]) and a 20% lower risk of major adverse cardiovascular events (HR 0.80 [0.75 to 0.86]) during a median follow-up of 6.0 months.
CONCLUSION: In this study, GLP-1 receptor agonist-SGLT-2 inhibitor combination was associated with a lower risk of major adverse liver and cardiovascular outcomes compared with either agent alone among patients with MASLD and T2D.
