Incretin-based drugs and the risk of acute liver injury among patients with type 2 diabetes mellitus

OBJECTIVE: To determine whether the use of dipeptidyl peptidase 4 (DPP-4) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs), separately, is associated with an increased risk of acute liver injury compared with the use of sodium-glucose co-transporter-2 (SGLT-2) inhibitors.

RESEARCH DESIGN AND METHODS: We used the United Kingdom Clinical Practice Research Datalink linked with the Hospital Episode Statistics Admitted Patient Care and the Office for National Statistics databases to assemble two new-user, active comparator cohorts. The first included 106,310 initiators of DPP-4 inhibitors and 27,277 initiators of SGLT-2 inhibitors, while the second included 9470 initiators of GLP-1 RAs and 26,936 initiators of SGLT-2 inhibitors. Cox proportional hazards models with propensity score fine stratification weighting were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of acute liver injury.

RESULTS: Compared with SGLT-2 inhibitors, DPP-4 inhibitors were associated with a 53% increased risk of acute liver injury (HR: 1.53, 95% CI: 1.02-2.30). In contrast, GLP-1 RAs were not associated with an overall increased risk of acute liver injury (HR: 1.11, 95% CI: 0.57-2.16). However, an increased risk was observed among female users of both DPP-4 inhibitors (HR: 3.22, 95% CI: 1.67-6.21) and GLP-1 RAs (HR: 3.23, 95% CI: 1.44-7.25).

CONCLUSIONS: In this population-based study, DPP-4 inhibitors were associated with an increased risk of acute liver injury compared with SGLT-2 inhibitors in patients with type 2 diabetes. In contrast, an increased risk of acute liver injury was observed only among female GLP-1 RA users.