Ertugliflozin Lowers UA, Improves Gout Outcomes in People With Type 2 Diabetes and ASCVD

Ertugliflozin was associated with lowering uric acid(UA) and improving gout-related outcomes compared with placebo in people with type 2 diabetes (T2D) and cardiovascular disease, according to a post-hoc analysis of the VERTIS CV (NCT01986881) trial.¹

“Hyperuricaemia and gout are associated with multiple comorbidities including T2D, hypertension, hyperlipidaemia and obesity, often coexisting as cardiovascular-kidney-metabolic syndrome.² Hyperuricaemia and gout are also associated with higher risk of atherosclerotic cardiovascular disease (ASCVD) and chronic kidney disease (CKD).This association between elevated UA levels and cardiovascular-kidney-metabolic syndrome may reflect activation of deleterious pathways and mechanisms including chronic inflammation, oxidative stress, endothelial dysfunction, and renin–angiotensin system upregulation, although it is unclear if UA plays a causal role in development of these conditions,” lead investigator Vikas S. Sridhar, MD, Toronto General Hospital Research Institute, University Health Network, Ontario, Canada, and colleagues wrote.¹

VERTIS CV randomized participants with T2D and ASCVD to placebo, ertugliflozin 5 mg or ertugliflozin 15 mg. Investigators evaluated mean UA over 260 weeks for pooled ertugliflozin versus placebo overall, and by baseline quintile of UA, glycated hemoglobin level, albuminuria status, estimated glomerular filtration rate and KDIGO (Kidney Disease: Improving Global Outcomes in Chronic Kidney Disease) risk category. They assessed the effect of ertugliflozin on a composite of gout onset or initiation of anti-gout medication.

At baseline, the placebo group had a mean UA level of 5.67 mg/dL and the ertugliflozin group had a mean UA level of 5.62 mg/dL. Sridhar and colleagues found that 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 (95% CI, −0.02 to 0.15) in the placebo group and −0.19 mg/dL (95% CI, −0.25 to −0.13) in the pooled ertugliflozin group. At Week 260, placebo-adjusted LSM change in UA from baseline was −0.26 mg/dL (95% CI, −0.36 to −0.16) with ertugliflozin.

They also found that ertugliflozin was associated with reductions in UA compared with placebo across baseline UA quintiles. Overall, the incidence of the composite of gout-related outcomes was 84/2539 (3.3%) for placebo and 133/5091 (2.6%) for ertugliflozin (hazard ratio for the composite 0.76 [95% CI, 0.580-1.002]; P = .052). Investigators found no differences in the treatment effect of ertugliflozin on gout-related outcomes in subgroups based on UA quintile, blood pressure-related characteristics, HbA1c, eGFR, UACR or KDIGO risk category.¹

“To conclude, treatment with ertugliflozin reduced levels of UA and numerically reduced rates of gout onset or initiation of anti-gout medications in people without a history of gout and not on anti-gout medications at baseline. The presence of risk factors for gout or, by extension, a diagnosis of established gout, may represent yet another reason for clinicians to consider SGLT2 inhibition in people with T2D. Prospective studies or, more realistically, large meta-analyses or real-world analyses are required to confirm whether ertugliflozin is associated with clinically meaningful reductions in gout-related outcomes in high-risk cohorts,” Sridhar and colleagues concluded.¹

REFERENCES

1. Sridhar VS, Cosentino F, Dagogo JS, et al. 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; 1-11. doi:10.1111/dom.15895
2. Stamp LK, Chapman PT. Gout and its comorbidities: implications for therapy. Rheumatology (Oxford). 2013; 52: 34-44.