Treatment with orforglipron, an oral glucagon like peptide-1 receptor agonist, is associated with improvements of CV risk biomarkers in participants with type 2 diabetes or obesity without diabetes.

IF 8.5 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS
Sean Wharton, Julio Rosenstock, Manige Konige, Yanzhu Lin, Kevin Duffin, Jonathan Wilson, Hiya Banerjee, Valentina Pirro, Christof Kazda, Kieren Mather
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引用次数: 0

Abstract

Background: Orforglipron, a novel oral, non-peptide glucagon like peptide-1 (GLP-1) receptor agonist, has demonstrated efficacy in improving body weight reduction and glycemic control. However, its potential benefits in improving cardiovascular (CV) risk factors have yet to be determined. We assessed the effect of orforglipron in participants with type 2 diabetes (T2D) and/or overweight or obesity on blood pressure, lipid, and inflammatory biomarkers associated with risk for major adverse cardiovascular events.

Methods: Using data from participants with available samples from Phase 2 trials of orforglipron in participants with T2D (N = 361) or with overweight or obesity without diabetes mellitus (N = 234), we performed an exploratory analysis of changes in CV risk markers. For the T2D study, participants mean age 59 years, 40% were assigned female at birth with a mean HbA1c of 8.1% and mean BMI of 35.3 kg/m2; they received once daily orforglipron doses (3, 12, 24, 36, or 45 mg) or once weekly subcutaneous dulaglutide 1.5 mg, or placebo. In the obesity study, participants had a mean age 54 years, 60% were assigned female at birth, and mean BMI was 37.9 kg/m2; they received once daily orforglipron (12, 24, 36, or 45 mg) or placebo. The change from baseline at 26 weeks (T2D study) or 36 weeks (obesity study) in blood pressure, lipids (cholesterol, triglycerides, Apolipoprotein B (ApoB), Apolipoprotein C3 (ApoC3), N-terminal pro-b-type natriuretic peptide (NT-pro-BNP), and inflammatory biomarkers (high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6)) were assessed.

Results: Significant placebo-adjusted decreases from baseline in blood pressure, low-density lipoprotein (LDL) cholesterol, triglycerides, ApoB, ApoC3, and hsCRP were observed following orforglipron treatment in participants with T2D and/or overweight or obesity. In both studies, improvements in blood pressure, lipid parameters, and most of the evaluated biomarkers were of similar magnitude after treatment with 12 mg orforglipron as with 24, 36, and 45 mg.

Conclusion: Orforglipron treatment was associated with beneficial changes in CV risk markers in participants with T2D and in participants with overweight/obesity without T2D. (Clinicaltrials.gov: NCT05048719, NCT05051579).

口服胰高血糖素样肽-1受体激动剂orforglipron治疗与2型糖尿病或非糖尿病肥胖患者心血管风险生物标志物的改善相关。
背景:Orforglipron是一种新型的口服非肽类胰高血糖素样肽-1 (GLP-1)受体激动剂,已被证明具有改善减肥和血糖控制的功效。然而,其在改善心血管(CV)危险因素方面的潜在益处尚未确定。我们评估了在2型糖尿病(T2D)和/或超重或肥胖患者中使用奥福格列酮对与主要不良心血管事件风险相关的血压、血脂和炎症生物标志物的影响。方法:利用来自奥福格列酮治疗t2dm患者(N = 361)或超重或肥胖无糖尿病患者(N = 234)的2期试验样本的数据,我们对CV危险标志物的变化进行了探索性分析。在T2D研究中,参与者平均年龄59岁,40%为女性,平均HbA1c为8.1%,平均BMI为35.3 kg/m2;他们接受每日一次的奥福格列酮剂量(3,12,24,36或45mg)或每周一次的杜拉鲁肽皮下注射(1.5 mg)或安慰剂。在肥胖研究中,参与者的平均年龄为54岁,60%出生时被指定为女性,平均BMI为37.9 kg/m2;他们每天接受一次orforglipron(12,24,36或45mg)或安慰剂。从26周(T2D研究)或36周(肥胖研究)的基线开始,评估血压、血脂(胆固醇、甘油三酯、载脂蛋白B (ApoB)、载脂蛋白C3 (ApoC3)、n端前B型利钠肽(NT-pro-BNP)和炎症生物标志物(高敏c反应蛋白(hsCRP)、白细胞介素6 (IL-6))的变化。结果:经安慰剂调整后,t2dm和/或超重或肥胖患者的血压、低密度脂蛋白(LDL)胆固醇、甘油三酯、ApoB、apo3和hsCRP较基线显著下降。在这两项研究中,12 mg奥福格列酮治疗后血压、血脂参数和大多数评估的生物标志物的改善程度与24、36和45 mg治疗后相似。结论:奥福列酮治疗与t2dm患者和超重/肥胖无t2dm患者心血管危险指标的有益改变相关。(Clinicaltrials.gov: NCT05048719, NCT05051579)。
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
Cardiovascular Diabetology
Cardiovascular Diabetology 医学-内分泌学与代谢
CiteScore
12.30
自引率
15.10%
发文量
240
审稿时长
1 months
期刊介绍: Cardiovascular Diabetology is a journal that welcomes manuscripts exploring various aspects of the relationship between diabetes, cardiovascular health, and the metabolic syndrome. We invite submissions related to clinical studies, genetic investigations, experimental research, pharmacological studies, epidemiological analyses, and molecular biology research in this field.
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