Dose‐dependent effects of oral semaglutide on arterial stiffness and the additive role of SGLT‐2 inhibitors in type 2 diabetes

AIMS: The cardio-ankle vascular index (CAVI) is a blood pressure-independent marker of arterial stiffness and a well-established predictor of cardiovascular (CV) events. The effects of oral semaglutide, particularly at low doses, on arterial stiffness remain unclear. METHODS: This single-centre retrospective study included 138 patients with type 2 diabetes mellitus who received oral semaglutide and underwent CAVI assessment at baseline and 6 months. ΔCAVI was defined as baseline minus follow-up CAVI. Therefore, a positive ΔCAVI indicates a decrease (i.e., improvement) in arterial stiffness. Semaglutide doses (3, 7 or 14 mg) were determined by treating physicians, and concomitant sodium-glucose cotransporter 2 (SGLT-2) inhibitor use was recorded. CV outcomes were monitored for up to 18 months after the 6-month evaluation. A ΔCAVI of ≥0.2 was defined as an effective response. Multivariable linear regression identified predictors of CAVI improvement. RESULTS: (median 27.4, interquartile range 24.7-30.8). In multivariable linear regression, concomitant SGLT-2 inhibitor use was associated with greater CAVI improvement (β = 0.51, 95% CI 0.05-0.98; p = 0.03). Oral semaglutide of 14 mg was associated with greater improvement than 3 and 7 mg, whereas higher baseline CAVI was associated with an attenuated response. Patients with ΔCAVI ≥0.2 did not show a statistically significant difference in CV events during follow-up compared with those without ΔCAVI ≥0.2 (p = 0.08). CONCLUSIONS: In this retrospective cohort, higher dose oral semaglutide, particularly in combination with SGLT-2 inhibitors, was associated with favourable changes in arterial stiffness.