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.

IF 5.4 2区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetes, Obesity & Metabolism Pub Date : 2024-09-02 DOI:10.1111/dom.15895

Vikas S Sridhar, Francesco Cosentino, Samuel Dagogo-Jack, Darren K McGuire, Richard E Pratley, Nilo B Cater, Margaret Noyes Essex, James P Mancuso, Yujie Zhao, David Z I Cherney

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引用次数: 0

Abstract

Aim: 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.

Materials and methods: 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.

Results: 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]).

Conclusions: Ertugliflozin was generally associated with lowering UA overall and across subgroups compared with placebo, and numerically reduced rates of gout-related outcome events.

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ertugliflozin对2型糖尿病和心血管疾病患者尿酸和痛风相关结果的影响：VERTIS CV的事后分析。

目的：对VERTIS CV（NCT01986881）试验进行事后分析，探讨厄曲酶对血清尿酸（UA）和痛风相关结果的影响：患有2型糖尿病和动脉粥样硬化性心血管疾病的参与者被随机（1:1:1）分配到安慰剂、5毫克厄曲酶或15毫克厄曲酶中。9毫克/分升[>345.0-410.4微摩尔/升]和>6.9毫克/分升[>410.4微摩尔/升]）、糖化血红蛋白水平、白蛋白尿状态、估计肾小球滤过率和KDIGO（肾脏病：改善慢性肾脏病的全球疗效）风险类别。评估了厄曲单抗对痛风发作或开始服用抗痛风药物的综合影响：结果：安慰剂组和厄曲酶单抗组基线时的平均尿酸水平分别为 5.67 和 5.62 mg/dL。与安慰剂相比，厄曲唑仑在第6-260周降低了UA，在第260周时，安慰剂组和厄曲唑仑联合组与基线相比的最小平方均值（LSM）变化（95%置信区间[CI]）分别为0.07 mg/dL (-0.02, 0.15)和-0.19 mg/dL (-0.25, -0.13)。在第 260 周，经安慰剂调整的 LSM 变化（95% CI）为-0.26 mg/dL (-0.36, -0.16)。与安慰剂相比，厄曲酶与基线UA五分位数的UA降低相关。安慰剂的痛风相关综合结果发生率为84/2539（3.3%），厄曲酶的发生率为133/5091（2.6%）（综合结果的危险比为0.76 [95% CI 0.580, 1.002]）：与安慰剂相比，厄曲唑嗪总体上能降低UA，在不同亚组中也能降低UA，并在数量上降低痛风相关结局事件的发生率。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Diabetes, Obesity & Metabolism 医学-内分泌学与代谢

CiteScore

10.90

自引率

6.90%

发文量

319

审稿时长

3-8 weeks

期刊介绍： Diabetes, Obesity and Metabolism is primarily a journal of clinical and experimental pharmacology and therapeutics covering the interrelated areas of diabetes, obesity and metabolism. The journal prioritises high-quality original research that reports on the effects of new or existing therapies, including dietary, exercise and lifestyle (non-pharmacological) interventions, in any aspect of metabolic and endocrine disease, either in humans or animal and cellular systems. ‘Metabolism’ may relate to lipids, bone and drug metabolism, or broader aspects of endocrine dysfunction. Preclinical pharmacology, pharmacokinetic studies, meta-analyses and those addressing drug safety and tolerability are also highly suitable for publication in this journal. Original research may be published as a main paper or as a research letter.