Study Links SGLT2 Inhibitor Use to Lower Risk of Gout in Patients With Type 2 Diabetes

Frontiers in Endocrinology published a systematic review and meta-analysis, which found the use sodium-glucose cotransporter-2 (SGLT2) inhibitors, a class of prescription medicines that are used with diet and exercise to lower blood sugar in adults with type 2 diabetes mellitus (TD2M), was associated with a 34% decreased risk of developing gout among patients with T2DM.

To conduct this study, a systematic review and meta-analysis were carried out in accordance with the PRISMA 2020 guidelines. Articles published between January 1, 2000, and December 31, 2022, were searched using the PubMed and Web of Science databases. The primary endpoint of interest was the incidence of gout, including gout flares, gout events, initiation of uric acid-lowering therapy, and use of anti-gout drugs, in T2DM patients using SGLT2 inhibitors compared with those not using SGLT2 inhibitors. The researchers used a random-effects model to estimate the combined hazard ratio (HR) along with a 95% CI in order to assess the relationship between the use of SGLT2 inhibitors and the risk of developing gout.

The study included 2 prospective post-hoc analyses of randomized controlled trials and 5 retrospective cohort studies utilizing electronic medical record-linkage. The analysis demonstrated a significant reduction in the risk of developing gout among patients with T2DM using SGLT2 inhibitors compared with those not using SGLT2 inhibitors. The pooled HR was estimated at 0.66 (95% CI, 0.57-0.76), indicating a 34% decreased risk of gout associated with SGLT2 inhibitor use.

The precise mechanisms responsible for the utilization of SGLT2 inhibitor and its potential for reducing gout risk remain unknown. As noted by the authors, these therapeutics function by inhibiting the reabsorption of glucose and sodium in the kidney’s proximal tubule. This action results in elevated excretion of glucose and sodium through urine, as well as an increase in urinary volume. Consequently, blood glucose levels are reduced. Additionally, the augmented urinary volume has the potential to improve the elimination of uric acid, offering a plausible explanation for the decrease in blood uric acid levels. Therefore, the authors posit that it is “a rational hypothesis that SGLT2 inhibitor reduces blood uric acid levels by enhancing urinary excretion of uric acid. Thus, the risk of gout is reduced after the use of SGLT2 inhibitors.”

To conclude their review, the authors emphasized the need for randomized controlled trials and real-world evidence are necessary to verify whether there exists a consistent pattern across the SGLT2 inhibitor class in reducing the risk of gout among patients with T2DM.

Source: Frontiers in Endocrinology