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GLP-1RA plus SGLT2i combination therapy and liver fibrosis progression in MASLD with type 2 diabetes

Jonggi Choi1,2,3, Gabby Mitchell4, Vy H Nguyen4

  • 1Division of Gastroenterology, Liver Center, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Hepatology Communications
|April 13, 2026
PubMed
Abstract

Insights

Combining glucagon-like peptide-1 receptor agonists (GLP-1RAs) with sodium-glucose cotransporter-2 inhibitors (SGLT2is) significantly reduced liver fibrosis progression in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes mellitus (T2DM). This combination therapy showed better outcomes than GLP-1RA monotherapy.

Area of Science:

  • Hepatology
  • Endocrinology
  • Pharmacology

Background:

  • Metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes mellitus (T2DM) are prevalent conditions often co-existing.
  • Liver fibrosis progression is a major concern in patients with MASLD and T2DM.
  • Combined therapy with GLP-1RAs and SGLT2is may offer synergistic benefits for liver health.

Purpose of the Study:

  • To evaluate the comparative effectiveness of GLP-1RA plus SGLT2i combination therapy versus GLP-1RA monotherapy.
  • To assess the impact on liver fibrosis progression in patients with MASLD and T2DM.
  • To analyze the incidence of hepatic complications as a secondary outcome.

Main Methods:

  • Retrospective cohort study utilizing data from Mass General Brigham (2010-2024).
  • Inclusion criteria: Adults with MASLD and T2DM initiating GLP-1RA therapy with low-to-intermediate FIB-4 scores.
  • Propensity score matching (1:2) was employed to compare combination therapy (n=879) with monotherapy (n=1690).

Main Results:

  • Combination therapy demonstrated a significantly lower risk of fibrosis progression (HR 0.76; 95% CI 0.61-0.95).
  • A numerically lower incidence of hepatic complications was observed with combination therapy (HR 0.76; 95% CI 0.53-1.09).
  • Subgroup and sensitivity analyses confirmed consistent protective effects of the combination therapy.

Conclusions:

  • GLP-1RA plus SGLT2i therapy is associated with reduced liver fibrosis progression in patients with MASLD and T2DM.
  • This combination represents a potentially effective strategy for managing liver disease in this patient population.
  • Further research may elucidate the precise mechanisms underlying these observed benefits.
Keywords:
GLP-1RAMASLDliver fibrosis

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