Vascular protective effects of diabetes medications that mimic or increase glucagon-like peptide-1 activity.

Angelica J Motta, Juraj Koska, Peter Reaven, Raymond Q Migrino
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引用次数: 13

Abstract

The incidence of type 2 diabetes (T2DM) is increasing rapidly worldwide and is a strong risk factor for cardiovascular disease (CVD) events. Although hyperglycemia is associated with increased CVD, intensive glycemic control with current diabetes medications has failed in recent large clinical trials to reduce macrovascular disease, demonstrating that intensive glucose control alone is insufficient to reduce major CVD events. A new approach to lowering glucose takes advantage of the incretin system and medications that raise or mimic glucagon-like peptide-1 (GLP-1). These agents not only improve glycemic control by mechanisms that minimize hypoglycemia, but also improve lipoprotein profiles, blood pressure control and weight loss. There is also increasing evidence that at least pharmacologic concentrations of GLP-1 or GLP-1 mimetics may improve endothelial function and have direct vascular-protective effects. Importantly, these benefits transpired even before the improvements in weight and overall glucose control occurred. It remains to be seen whether the chronic effects of GLP-1 activity on glucose, CVD risk factors and vascular function will lead to lasting beneficial effects on CVD risk. If preliminary findings on the vasculoprotective effects of GLP-1 agents are validated and confirmed in longitudinal clinical trials, this class of drugs may represent a paradigm shift in the treatment of vascular disease in both patients with diabetes and in non-diabetic individuals at high risk for CVD. Recent patents regarding GLP-1 agents are discussed in this review article.

模拟或增加胰高血糖素样肽-1活性的糖尿病药物的血管保护作用。
2型糖尿病(T2DM)的发病率在全球范围内迅速增加,是心血管疾病(CVD)事件的一个重要危险因素。虽然高血糖与CVD的增加有关,但在最近的大型临床试验中,强化血糖控制与目前的糖尿病药物在减少大血管疾病方面失败了,这表明单独强化血糖控制不足以减少主要的CVD事件。一种新的降糖方法利用肠促胰岛素系统和提高或模拟胰高血糖素样肽-1 (GLP-1)的药物。这些药物不仅通过最小化低血糖的机制改善血糖控制,而且还改善脂蛋白谱、血压控制和体重减轻。也有越来越多的证据表明,至少药理学浓度的GLP-1或GLP-1模拟物可以改善内皮功能并具有直接的血管保护作用。重要的是,这些益处甚至在体重改善和整体血糖控制发生之前就已经出现了。GLP-1活性对葡萄糖、心血管疾病危险因素和血管功能的慢性影响是否会导致对心血管疾病风险的持久有益影响,还有待观察。如果GLP-1药物的血管保护作用的初步发现在纵向临床试验中得到验证和证实,这类药物可能代表糖尿病患者和心血管疾病高风险非糖尿病患者治疗血管疾病的范式转变。本文对近年来有关GLP-1药物的专利进行了综述。
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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