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Adverse Liver and Renal Outcomes After Initiating SGLT-2i and GLP-1RA Therapy Among Patients With Diabetes and MASLD

Arunkumar Krishnan1,2, Carolin V Schneider3, Diptasree Mukherjee4

  • 1Department of Medicine, Wake Forest University School of Medicine, Winston Salem, North Carolina, USA.

Journal of Diabetes
|April 27, 2025
PubMed
Abstract

Insights

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) show reduced liver and kidney complications in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes mellitus (T2DM). These findings suggest SGLT2i are a preferred treatment for managing MASLD and T2DM complications.

Area of Science:

  • Hepatology
  • Nephrology
  • Endocrinology

Background:

  • Management of metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes mellitus (T2DM) is complex, focusing on preventing liver and kidney complications.
  • Identifying effective anti-diabetic medications is crucial for improving outcomes in patients with both MASLD and T2DM.

Purpose of the Study:

  • To compare liver and renal outcomes in new users of sodium-glucose cotransporter 2 inhibitors (SGLT2i) versus other anti-diabetic drugs.
  • To evaluate the efficacy of SGLT2i, glucagon-like peptide-1 receptor agonists (GLP-1RA), dipeptidyl peptidase-4 inhibitors (DPP4i), and other anti-diabetic medications in patients with MASLD and T2DM.

Main Methods:

  • Retrospective cohort study utilizing electronic health records.
  • Propensity score-matched analysis of 88,306 patients with MASLD and T2DM initiating various anti-diabetic medications.
  • Primary outcomes included cirrhosis, hepatic decompensations, and hepatocellular carcinoma; secondary outcomes involved chronic kidney disease (CKD) progression and hemodialysis.

Main Results:

  • SGLT2i users showed reduced risks of cirrhosis, hepatic decompensations, and hepatocellular carcinoma compared to DPP4i users.
  • SGLT2i demonstrated significantly lower CKD progression (stages 4-5) and reduced need for hemodialysis compared to DPP4i.
  • SGLT2i also showed a lower risk of CKD progression and need for hemodialysis compared to GLP-1RA, with no significant difference in hepatic outcomes between SGLT2i and GLP-1RA.

Conclusions:

  • Sodium-glucose cotransporter 2 inhibitors (SGLT2i) significantly reduce liver complications in patients with MASLD and T2DM.
  • SGLT2i demonstrate a favorable impact on renal outcomes, including reduced CKD progression and hemodialysis requirements.
  • These findings support the preferential use of SGLT2i for managing MASLD and T2DM, particularly for preventing liver and kidney disease progression.
Keywords:
DPP4 inhibitorsGLP1MASLDSGLT2 inhibitorsT2DMchronic kidney diseasecirrhosishepatocellular carcinomaliver outcomesrenal outcomes

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