Lower risk of gout in sodium glucose cotransporter 2 (SGLT2) inhibitors versus dipeptidyl peptidase-4 (DPP4) inhibitors in type-2 diabetes

Rheumatology (Oxford). 2023 Apr 3;62(4):1501-1510. doi: 10.1093/rheumatology/keac509.

Abstract

Objectives: The effects of sodium-glucose cotransporter 2 inhibitors (SGLT2I) vs dipeptidyl peptidase-4 inhibitors (DPP4I) on the risk of new-onset gout remains unknown. This study aims to compare the effects of SGLT2I against DPP4I on gout risks.

Methods: This was a retrospective population-based cohort study of patients with type-2 diabetes mellitus treated with SGLT2I or DPP4I between 1 January 2015 and 31 December 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 models were conducted. Competing risks models and multiple approaches based on the propensity score were applied.

Results: This study included 43 201 patients [median age: 63.23 years old (Interquartile range, IQR): 55.21-71.95, 53.74% males; SGLT2I group: n = 16 144; DPP4I group: n = 27 057] with a median follow-up of 5.59 years (IQR: 5.27-5.81 years) since initial drug exposure. The incidence rate of developing gout [Incidence rate (IR): 2.5; 95% CI: 2.2, 2.9] among SGLT2I users was significantly lower than DPP4I users (IR: 5.2; 95% CI: 4.8, 5.8). SGLT2I was associated with 51% lower risks of gout (HR: 0.49; 95% CI: 0.42, 0.58; P-value < 0.0001) and 51% lower risks of all-cause mortality (HR: 0.49; 95% CI: 0.42, 0.58; P-value < 0.0001) after adjusting for significant demographics, past comorbidities, medications and laboratory results. The results remained consistent on competing risk and other propensity score approaches.

Conclusions: SGLT2I use was associated with lower risks of new gout diagnosis compared with DPP4I use.

Keywords: DPP4; SGLT2; anti-diabetic drugs; cohort study; crystalline arthropathy; diabetes mellitus; gout; metabolic syndrome; mortality; retrospective study.

MeSH terms

  • Cohort Studies
  • Diabetes Mellitus, Type 2* / complications
  • Dipeptidyl Peptidase 4 / therapeutic use
  • Dipeptidyl-Peptidase IV Inhibitors* / pharmacology
  • Dipeptidyl-Peptidase IV Inhibitors* / therapeutic use
  • Female
  • Gout* / complications
  • Gout* / drug therapy
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Male
  • Middle Aged
  • Retrospective Studies
  • Sodium-Glucose Transporter 2 / therapeutic use
  • Sodium-Glucose Transporter 2 Inhibitors* / pharmacology
  • Sodium-Glucose Transporter 2 Inhibitors* / therapeutic use

Substances

  • Dipeptidyl-Peptidase IV Inhibitors
  • Hypoglycemic Agents
  • Sodium-Glucose Transporter 2 Inhibitors
  • Dipeptidyl Peptidase 4
  • Sodium-Glucose Transporter 2