Patients taking sodium-glucose cotransporter 2 (SGLT2) inhibitors had lower rates of gout flares, a meta-analysis found. The analysis included five randomized controlled trials (RCTs) of the drug class, with 29,776 patients, most with type 2 diabetes. A total of 1,052 gout-related events were identified, and SGLT2 inhibitor use was significantly associated with reduced risk of composite gout outcomes. Treatment benefits did not differ by whether patients had heart failure (HF) or diabetes.
The study was published by Diabetes, Obesity and Metabolism on June 19. The following commentary by Katarzyna Nabrdalik, MD, PhD, and Gregory Y.H. Lip, MD, was published in the ACP Journal Club section of Annals of Internal Medicine on Nov. 7.
The scope of SGLT2 inhibitor use has expanded, and these drugs are now recommended not only in type 2 diabetes, but also in HF regardless of the presence of type 2 diabetes. This reflects the cardioprotective properties of SGLT2 inhibitors, which seem to be independent of glycemic control. The meta-analysis of RCTs by Banerjee and colleagues showed a risk reduction for gout outcomes with SGLT2 inhibitors (hazard ratio, 0.55), not only in patients with type 2 diabetes, which was previously seen, but also in patients with HF.
There were differences in baseline serum uric acid (SUA) levels between patients with diabetes and those with HF, which could be due to higher use of diuretics and worse kidney function in the latter group. However, meta-regression showed that neither baseline SUA levels nor lowering of SUA levels influenced SGLT2 inhibitor effects. This observation is new and suggests SGLT2 inhibitor effects are uric acid–independent. The drug action could be related to anti-inflammatory effects expressed through elevated circulating levels of ketone bodies with attenuated nucleotide-binding oligomerization domain–like receptor P3 inflammasome activation and interleukin-1β secretion, similar to the cardioprotective effects of the anti-inflammatory mechanisms in type 2 diabetes with cardiovascular complications.
Although the meta-analysis by Banerjee and colleagues was based on post hoc analyses of RCTs done for reasons other than evaluating effects on gout, it may point to the need for further RCTs evaluating SGLT2 inhibitors in this setting. Nonetheless, the analysis highlights the generality of SGLT2 inhibitor use in patients with type 2 diabetes or HF and may help to avoid polypharmacy when treatment for gout is also needed.