Comparison of Sodium-Glucose Cotransporter-2 Inhibitor and Dipeptidyl Peptidase-4 Inhibitor on the Risks of New-Onset Atrial Fibrillation, Stroke and Mortality in Diabetic Patients: A Propensity Score-Matched Study in Hong Kong

Objective To compare the effects of sodium-glucose cotransporter 2 inhibitors (SGLT2Is) and dipeptidyl peptidase-4 inhibitors (DPP4Is) on adverse outcomes in diabetic patients in Hong Kong.

Methods This was a retrospective population-based cohort study of type 2 diabetes mellitus patients (n=72,746) treated with SGLT2I or DPP4I between January 1, 2015, and December 31, 2020, in Hong Kong. Patients with exposure to both DPP4I and SGLT2I therapy, without complete demographics or mortality data, or who had prior atrial fibrillation (AF) were excluded. The study outcomes were new-onset AF, stroke/transient ischemic attack, cardiovascular mortality and all-cause mortality. Propensity score matching (1:1 ratio) between SGLT2I and DPP4I users was performed.

Results The unmatched study cohort included 21,713 SGLT2I users and 39,510 DPP4I users (total: n=61,233 patients; 55.37% males, median age: 62.7 years [interquartile range (IQR): 54.6–71.9 years]). Over a median follow-up of 2030 (IQR:1912–2117) days, 2496 patients (incidence rate [IR]: 4.07%) developed new-onset AF, 2179 patients (IR: 3.55%) developed stroke/transient ischemic attack, 1963 (IR: 3.20%) died from cardiovascular causes and 6607 patients (IR: 10.79%) suffered from all-cause mortality. After propensity score matching (SGLT2I: n=21,713; DPP4I: n=21,713), SGLT2I users showed lower incidence of new-onset AF (1.96% vs. 2.78%, standardized mean difference [SMD]=0.05), stroke (1.80% vs.3.52%, SMD=0.11), cardiovascular mortality (0.47% vs. 1.56%, SMD=0.11) and all-cause mortality (2.59% vs. 7.47%, SMD=0.22) compared to DPP4I users. Cox regression found that SGLT2I users showed lower risk of new-onset AF (hazard ratio [HR]: 0.68, 95% confidence interval [CI]: [0.56, 0.83], P=0.0001), stroke (HR: 0.64, 95% CI: [0.53, 0.79], P<0.0001), cardiovascular mortality (HR: 0.39, 95% CI: [0.27, 0.56], P<0.0001) and all-cause mortality (HR: 0.44, 95% CI: [0.37, 0.51], P<0.0001) after adjusting for significant demographics, past comorbidities, medications and laboratory tests.

Conclusions Based on real-world data of type 2 diabetic patients in Hong Kong, SGLT2I use was associated with lower risk of incident AF, stroke/transient ischemic attack, and cardiovascular and all-cause mortality outcomes compared to DPP4I use.