Impact of oral semaglutide on serum urate levels in people with type 2 diabetes: A retrospective real-world analysis (URISEMA study)

Abstract

Background

Evidence on the effects of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on serum urate (SU) levels in people with type 2 diabetes (PWT2D) is limited. This study investigates the effect of oral semaglutide on SU levels.

Methods

Retrospective, observational study including PWT2D who were prescribed oral semaglutide. The primary endpoint was achieving SU levels below 6 mg/dL at 12 months of follow-up (FU). Secondly, we assessed baseline factors associated with achieving SU levels of <6 mg/dL and average reductions in SU levels.

Results

The study included 236 patients (median age 64 years, BMI 33.8 kg/m², HbA1c 7.6 %, 40.7 % women, 52.3 % on SGLT2 inhibitors). Baseline SU was 5.2 mg/dL, 66.1 % had SU levels <6 mg/dL, and 23.7 % had hyperuricemia. Under oral semaglutide, 70.7 % and 76 % showed SU <6 mg/dL at 6 and 12 months, respectively. After multivariate adjustment, only SU ≥7 mg/dL (OR 4.54, 95 %CI 1.08–19.25) and switching from a DPP-4 inhibitor (OR 6.53, 95 %CI 1.57–27.32) were associated with achieving the SU target. SU decreased by 0.1 mg/dL after 6 months (p = 0.52) and by 0.2 mg/dL (p = 0.01) at 12 months FU. Greater reductions were observed in those with baseline SU >6 mg/dL (0.6 mg/dL and 0.8 mg/dl, respectively; all p < 0.001). Changes in SU levels were independent of improved metabolic control, weight loss, or baseline use of GLP-1 RAs or SGLT2 inhibitors.

Conclusion

Oral semaglutide in real-world settings showed a modest reduction in SU levels in PWT2D, particularly linked to baseline hyperuricemia (with notable reduction figures) and switching from DPP-4 inhibitors.