Glucagon-Like Peptide 1 Receptor Agonists and Sodium–Glucose Cotransporter 2 Inhibitors and the Prevention of Cirrhosis Among Patients With Type 2 Diabetes

Jan 8, 2025Diabetes care

Medications that lower blood sugar and their link to preventing liver scarring in people with type 2 diabetes

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Abstract

SGLT-2 inhibitors are associated with a lower risk of cirrhosis compared to DPP-4 inhibitors in patients with type 2 diabetes.

GLP-1 receptor agonists (GLP-1RAs) were not linked to a reduced incidence of cirrhosis compared to DPP-4 inhibitors.
SGLT-2 inhibitors showed a 36% reduction in the incidence of cirrhosis compared to DPP-4 inhibitors.
SGLT-2 inhibitors were also associated with a reduced incidence of decompensated cirrhosis, although findings were not statistically significant.
Neither GLP-1RAs nor SGLT-2 inhibitors were associated with a lower risk of hepatocellular carcinoma or liver-related mortality.

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OBJECTIVE: To determine whether glucagon-like peptide 1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter 2 (SGLT-2) inhibitors, separately, compared with dipeptidyl peptidase 4 (DPP-4) inhibitors are associated with a reduced risk of cirrhosis and other adverse liver outcomes among patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS: With an active comparator, new-user approach, we conducted a cohort study using the U.K. Clinical Practice Research Datalink linked with hospital and national statistics databases. Cox proportional hazards models using propensity score fine stratification weighting were used to calculate hazard ratios (HRs) and 95% CIs for cirrhosis (primary outcome) and decompensated cirrhosis, hepatocellular carcinoma, and liver-related mortality (secondary outcomes).

RESULTS: In the first cohort comparing 25,516 patients starting GLP-1RAs and 186,752 starting DPP-4 inhibitors, GLP-1RAs were not associated with the incidence of cirrhosis (HR 0.90, 95% CI 0.68-1.19) or the secondary outcomes. In a separate cohort comparing 33,161 patients starting SGLT-2 inhibitors and 124,431 starting DPP-4 inhibitors, SGLT-2 inhibitors were associated with a reduced incidence of cirrhosis (HR 0.64, 95% CI 0.46-0.90), as also decompensated cirrhosis (HR 0.74, 95% CI 0.54-1.00), but not with a lower risk of hepatocellular carcinoma or liver-related mortality.

CONCLUSIONS: In patients with type 2 diabetes in the U.K., GLP-1RAs were not associated with a lower risk of cirrhosis compared with DPP-4 inhibitors in patients with type 2 diabetes. However, SGLT-2 inhibitors were associated with a lower risk of cirrhosis compared with DPP-4 inhibitors.

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Glucagon-Like Peptide 1 Receptor Agonists and Sodium–Glucose Cotransporter 2 Inhibitors and the Prevention of Cirrhosis Among Patients With Type 2 Diabetes

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