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

Abstract

ObjectiveTo assess the relationship between use of sodium-glucose cotransporter-2 inhibitors (SGLT2i) and the risk of gout among patients with type 2 diabetes mellitus (T2DM).MethodsA systemic review and meta-analysis were designed by reviewing articles published between 2000 January 1 and 2022 December 31 using PubMed system and Web of Science system based on the PRISMA 2020 guidelines. The end point of interest was gout (including gout flares, gout events, starting uric-acid lowering therapy and starting anti-gout drugs use) among patients with T2DM using SGLT2i versus not using SGLT2i. A random-effects model was utilized to measure the pooled hazard ratio (HR) with 95% confidence interval (CI) for the risk of gout associated with SGLT2i use.ResultsTwo prospective post-hoc analyses of randomized controlled trials and 5 retrospective electronic medical record-linkage cohort studies met the inclusion criteria. The meta-analysis demonstrated that there was a decreased risk of developing gout for SGLT2i use as comparing with non-use of SGLT2i among patients with T2DM (pooled HR=0.66 and 95%CI=0.57-0.76).ConclusionsThis meta-analysis demonstrates that SGLT2i use is associated with a 34% decreased risk of developing gout among patients with T2DM. SGLT2i may be the treatment options for patients with T2DM who are at high risk of gout. More randomized controlled trials and real-world data are needed to confirm whether there is a class effect of SGLT2i for the risk reduction of gout among patients with T2DM.

Sodium glucose cotransporter-2 inhibitors and heart disease: Current perspectives

“…By preventing reabsorption, SGLT2i can increase the concentration of glucose reaching the collecting ducts, which in turn compete with urate for reabsorption via the GLUT9 isoform 2 leading to the excretion of more uric acid. Other mechanisms involving activation of the xanthine oxidase by sirtuin activation and alteration of URAT1 transporter have been also proposed[ 32 ]. In a nationwide study from Taiwan, that investigated the association, the use of SGLT2i was associated with a lower incidence of gout (HR: 0.89; 95%CI: 0.82-0.96) than DPP4 inhibitors, and this was particularly seen in patients receiving dapagliflozin[ 33 ].…”

Effects of sodium-glucose cotransporter-2 (SGLT-2) inhibitors on serum uric acid levels in patients with chronic kidney disease: a systematic review and network meta-analysis

“…Notably, there is growing evidence of the potential benefits of SGLT-2 inhibitors for lowering serum uric acid levels 18 19. A recent meta-analysis showed that in patients with diabetes mellitus, the risk of gout was reduced in those using SGLT-2 inhibitors compared with those not using SGLT-2 inhibitors (HR 0.66, 95% CI 0.57 to 0.76) 20. However, there is no comparison of the effects of different SGLT-2 inhibitors on serum uric acid levels in patients with CKD.…”