Ertugliflozin Lowers Uric Acid and Reduces Gout Risk in Type 2 Diabetes Patients with CVD, VERTIS CV Analysis

"Given these findings, clinicians might contemplate incorporating SGLT2 inhibitors into the treatment plan for individuals with type 2 diabetes who are at risk for gout or have already been diagnosed with the condition," the researchers wrote in Diabetes, Obesity and Metabolism.

Ertugliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, is primarily known for its effectiveness in glycemic control. Vikas S. Sridhar, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada, and colleagues performed post hoc analyses of the VERTIS CV trial to investigate the impact of ertugliflozin on serum uric acid levels and outcomes related to gout.

For this purpose, participants with type 2 diabetes and atherosclerotic cardiovascular disease were randomly assigned in a 1:1:1 ratio to receive either placebo, ertugliflozin 5 mg, or ertugliflozin 15 mg. Over 260 weeks, the mean serum UA levels were assessed for pooled ertugliflozin versus placebo, both overall and within specific baseline UA quintiles (≤4.3 mg/dL, >4.3–5.1 mg/dL, >5.1–5.8 mg/dL, >5.8–6.9 mg/dL, and >6.9 mg/dL).

The evaluation also considered glycated hemoglobin levels, albuminuria status, estimated glomerular filtration rate, and KDIGO (Kidney Disease: Improving Global Outcomes in Chronic Kidney Disease) risk category. Additionally, the impact of ertugliflozin on the composite outcome of gout onset or the initiation of anti-gout medication was examined.

Based on the study, the researchers revealed the following findings:

• The mean UA levels at baseline were 5.67 and 5.62 mg/dL in the placebo and ertugliflozin groups, respectively.
• Ertugliflozin reduced UA over Weeks 6–260 compared with placebo, with least squares mean (LSM) changes from baseline at Week 260 of 0.07 mg/dL and −0.19 mg/dL in the placebo and pooled ertugliflozin groups, respectively.
• At Week 260, placebo-adjusted LSM change from baseline in UA was −0.26 mg/dL with ertugliflozin.
• Ertugliflozin was associated with reductions in UA across baseline UA quintiles compared with placebo.
• The incidence of the composite of gout-related outcomes was 3.3% for placebo and 2.6% for ertugliflozin (hazard ratio for the composite 0.76).

The findings showed that treatment with ertugliflozin was associated with reduced uric acid levels and a numerical decrease in the rates of gout onset or initiation of anti-gout medications among individuals without a history of gout and not on such medications at baseline. This suggests that the presence of gout risk factors or an established diagnosis of gout could provide additional reasons for clinicians to consider SGLT2 inhibition for individuals with type 2 diabetes.

"To determine if ertugliflozin offers clinically significant reductions in gout-related outcomes for high-risk populations, further prospective studies or large-scale meta-analyses, as well as real-world analyses, are needed," the researchers concluded.

Reference:

Sridhar VS, Cosentino F, Dagogo-Jack S, McGuire DK, Pratley RE, Cater NB, Noyes Essex M, Mancuso JP, Zhao Y, Cherney DZI. Effects of ertugliflozin on uric acid and gout-related outcomes in persons with type 2 diabetes and cardiovascular disease: Post hoc analyses from VERTIS CV. Diabetes Obes Metab. 2024 Sep 2. doi: 10.1111/dom.15895. Epub ahead of print. PMID: 39219437.