Objective:

To evaluate the comparative effectiveness of GLP-1 RA plus SGLT2i combination therapy versus GLP-1 RA monotherapy versus SGLT2i monotherapy for mortality, cardiovascular, and hepatic outcomes in patients with MASLD and T2DM.

Approach:

• Study Design: Conducted as a target trial emulation following TARGET reporting guidelines, emulating three pairwise trials with a 5-year follow-up.
• Data Source: Utilized the TriNetX Research Network, accessing electronic health records from 110 healthcare organizations across the U.S.
• Eligibility Criteria: Included adults aged 18+ with ICD-10-CM codes for MASLD and T2DM, excluding those with competing liver disease etiologies.
• Treatment Strategies: Defined treatment strategies based on ATC classification codes, with combination therapy identified by overlapping prescriptions within a 30-day window.

Key Findings:

• MASLD prevalence is approximately 32.4% globally.
• Patients with concurrent MASLD and T2DM have higher rates of hepatic fibrosis progression and cardiovascular mortality compared with those with either condition alone.
• GLP-1 RAs have shown improvements in cardiovascular outcomes and established hepatoprotective effects, while SGLT2is have demonstrated cardiovascular and renal protection.

Interpretation:

The study addresses the comparative effectiveness of combination therapy versus monotherapy in patients with MASLD and T2DM.

Limitations:

• No randomized controlled trials have directly compared the therapies in this population.
• Prior studies lacked adequate confounding control and longer follow-up.

Conclusion:

The study seeks to provide insights into the comparative effectiveness of GLP-1 RA and SGLT2i therapies in patients with MASLD and T2DM.