The expanding use of newer glucose-lowering therapies has increased the need for large-scale postmarketing safety surveillance. A nationwide cohort study published in Diabetes Research and Clinical Practice evaluated adverse event signals associated with sodium-glucose co-transporter 2 inhibitors (SGLT2i), glucagon-like peptide 1 receptor agonists (GLP-1 RA), and dipeptidyl peptidase 4 inhibitors (DPP-4i).

The study used an active comparator, new-user cohort design and included initiators of the three drug classes identified through Danish nationwide registries. Investigators assessed multiple potential adverse event associations across treatment groups.

The analysis included 49,365 SGLT2i initiators, 33,018 GLP-1 RA initiators, and 50,531 DPP-4i initiators.

Findings

• SGLT2i initiators had higher risks of phimosis compared with GLP-1 RA users (hazard ratio [HR], 1.69; 95% confidence interval [CI], 1.42-2.02) and DPP-4i users (HR, 2.19; 95% CI, 1.84-2.59).
• SGLT2i use was also associated with higher risk of secondary polycythaemia compared with GLP-1 RA users (HR, 2.67; 95% CI, 1.62-4.38).
• DPP-4i initiators had increased risks of bacterial intestinal infections compared with SGLT2i users (HR, 1.56; 95% CI, 1.18-2.08) and GLP-1 RA users (HR, 2.08; 95% CI, 1.49-2.94).
• GLP-1 RA initiators demonstrated an elevated uterine cancer risk signal compared with SGLT2i users (HR, 1.82; 95% CI, 1.20-2.78) and DPP-4i users (HR, 1.94; 95% CI, 1.19-3.16).

Several potential safety signals were identified across newer glucose-lowering therapies in this nationwide registry analysis. Although some findings may reflect residual confounding, infection-related and cancer-related signals warrant further investigation.