The effect of sodium‐glucose cotransporter 2 inhibitors on HbA1c variability and cardiovascular and renal adverse outcome in patients with T2DM

AIMS: To compare the effectiveness of sodium-glucose cotransporter 2 (SGLT2) inhibitors and dipeptidyl peptidase 4 (DPP-4) inhibitors in reducing haemoglobin A1c (HbA1c) variability and improving cardiovascular and renal outcomes in patients with type 2 diabetes mellitus (T2DM) and high HbA1c variability. METHODS: This territory-wide cohort study involved patients with T2DM and an HbA1c variability score (HVS) >60% who initiated SGLT2 inhibitors or DPP-4 inhibitors in Hong Kong between 2015 and 2022. Propensity score (PS) matching was used to adjust for confounders. The primary outcome was post-treatment HVS within 3 years. Secondary outcomes included major adverse cardiovascular events (MACE) and serious renal events (SRE). RESULTS: Among 20,205 T2DM patients with a baseline HVS >60%, 4,612 SGLT2 inhibitor users were 1:1 matched with DPP-4 inhibitor users. When referencing the 0%-20% quintile, patients initiating SGLT2 inhibitors versus DPP-4 inhibitors exhibited a reduced likelihood of being in higher HVS quintiles [21%-40%: odds ratio (OR) 0.76, 95% confidence interval (CI) 0.66-0.88; 41%-60%: OR 0.57, 95% CI 0.50-0.65; 61%-80%: OR 0.49, 95% CI 0.42-0.56; and 81%-100%: OR 0.40, 95% CI 0.34-0.47]. SGLT2 inhibitors were associated with a reduced risk of MACE [hazard ratio (HR) 0.69; 95% CI 0.60-0.79] and SRE (HR 0.71; 95% CI 0.63-0.80) compared to DPP-4 inhibitors. CONCLUSION: In patients with high HbA1c variability, SGLT2 inhibitor initiation was associated with superior effectiveness in reducing HbA1c variability compared to DPP-4 inhibitors. The initiation of SGLT2 inhibitors versus DPP-4 inhibitors was linked to significantly reduced cardiovascular and renal adverse events.