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.

Abstract

To conduct post hoc analyses of the VERTIS CV (NCT01986881) trial to explore the effects of ertugliflozin on serum uric acid (UA) and gout-related outcomes. Participants with type 2 diabetes and atherosclerotic cardiovascular disease were randomised (1:1:1) to placebo, ertugliflozin 5 mg or ertugliflozin 15 mg. Mean UA over time (260 weeks) was evaluated for pooled ertugliflozin versus placebo overall, and by baseline quintile of UA (≤4.3 mg/dL [≤255.8 µmol/L], >4.3-5.1 mg/dL [>255.8-303.4 µmol/L], >5.1-5.8 mg/dL [>303.4-345.0 µmol/L], >5.8-6.9 mg/dL [>345.0-410.4 µmol/L] and >6.9 mg/dL [>410.4 µmol/L]), glycated haemoglobin level, albuminuria status, estimated glomerular filtration rate and KDIGO (Kidney Disease: Improving Global Outcomes in Chronic Kidney Disease) risk category. The effect of ertugliflozin on a composite of gout onset or initiation of anti-gout medication was assessed. 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 (95% confidence interval [CI]) from baseline at Week 260 of 0.07 mg/dL (-0.02, 0.15) and -0.19 mg/dL (-0.25, -0.13) in the placebo and pooled ertugliflozin groups, respectively. At Week 260, placebo-adjusted LSM change (95% CI) from baseline in UA was -0.26 mg/dL (-0.36, -0.16) 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 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]). Ertugliflozin was generally associated with lowering UA overall and across subgroups compared with placebo, and numerically reduced rates of gout-related outcome events.