Lower risk of gout in sodium glucose cotransporter 2 (SGLT2) inhibitors versus dipeptidyl peptidase-4 (DPP4) inhibitors in type-2 diabetes patients: a propensity score-matched study

Abstract

Background The effects of sodium-glucose cotransporter 2 inhibitors (SGLT2I) versus dipeptidyl peptidase-4 inhibitors (DPP4I) on the risk of new gout diagnosis have not been explored. This study aims to compare the effects of SGLT2I against DPP4I on gout risks in a Chinese population. Methods This was a retrospective population-based cohort study of patients with type-2 diabetes mellitus treated with SGLT2I or DPP4I between January 1st, 2015 and December 31st, 2020 in Hong Kong. The study outcomes are new-onset gout and all-cause mortality. Propensity score matching (1:1 ratio) between SGLT2I and DPP4I was performed. Univariable and multivariable Cox regression analysis models were conducted. Competing risks models and multiple approaches based on the propensity score were applied. Patients This study included 60996 patients (median age: 62.3 years old, 54.96% males; SGLTI group: n=21690; DPP4I group: n=39306). Results In the matched cohort, 1096 developed gout (IR: 2.52%) and 2195 died (IR: 5.05%). Univariable Cox regression showed that SGLT2I use was associated with lower risks of new diagnosis of gout (hazard ratio [HR]: 0.34; 95% confidence interval [CI]: 0.30–0.39; P-value<0.0001) and all-cause mortality (HR: 0.35; 95% CI: 0.32–0.39; P-value<0.0001) compared to DPP4I. The associated remained for both new diagnosis of gout (HR: 0.46; 95% CI: 0.37–0.57; P-value<0.0001) and all-cause mortality (HR: 0.38; 95% CI: 0.33–0.44; P-value<0.0001) after adjusting for significant demographics, past comorbidities, and non-SGLT2I/DPP4I medications. The risks of gout were lowered in each types of SGLT2I. The results were consistent on competing risk and other propensity score approaches analyses. Conclusions SGLT2I use was associated with lower risks of new gout diagnosis compared to DPP4I use. Funding Acknowledgement Type of funding sources: None.

Sodium-glucose cotransporter-2 inhibitors use and the risk of gout: a systematic review and meta-analysis

“…demonstrated a lower HR for gout associated with SGLT2i use as comparing with placebo, with reaching statistical significance (HR=0.53 and HR=0.67, respectively) ( 15 , 16 ). The 4 retrospective electronic medical record-linkage cohort studies demonstrated a lower HR for gout associated with SGLT2i use as comparing with GLP1RA use or DPP4i use, with reaching statistical significance ( 17 – 20 ). But one retrospective electronic medical record-linkage cohort study by Subramanian et al.…”

“…However, clinical data demonstrated conflicting results about the relation between SGLT2i use and the risk of gout. Some demonstrated benefit ( 15 – 20 ), but some demonstrated no benefit ( 21 ). For example, a prospective post-hoc analysis of randomized controlled trials by Li et al.…”

“…However, clinical data demonstrated conflicting results about the relation between SGLT2i use and the risk of gout. Some demonstrated benefit (15)(16)(17)(18)(19)(20), but some demonstrated no benefit (21). For example, a prospective post-hoc analysis of randomized controlled trials by Li et al demonstrated that canagliflozin use (one SGLT2i) correlated with a reduced risk of gout in persons with T2DM (hazard ratio=0.53, 95% confidence interval=0.40-0.71) (15).…”