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GLP-1 激动剂在肥胖的 HIV 感染者中的应用:是否存在潜在获益?

GLP-1 agonists for people living with HIV and obesity, is there a potential?

机构信息

Radboud University Medical Center, Department of Pharmacy and Radboudumc Research Institute for Medical Innovation (RIMI), Nijmegen, The Netherlands.

Radboud University Medical Center, Department of Internal Medicine and Radboudumc Research Institute for Medical Innovation (RIMI), Nijmegen, The Netherlands.

出版信息

HIV Med. 2023 Oct;24(10):1029-1034. doi: 10.1111/hiv.13521. Epub 2023 Jun 20.

Abstract

BACKGROUND AND OBJECTIVES

Obesity trends and metabolic dysregulation are rising in people living with HIV using antiretrovirals (ARVs). Underlying causes and preventive strategies are being investigated. Two glucagon like-peptide 1 (GLP-1) agonists, liraglutide and semaglutide, were formerly approved as glucose-lowering drugs and have been recently approved for long-term weight loss in people with obesity. Due to the lack of therapeutic guidelines or clinical trials in people with HIV, we discuss the potential benefits, safety aspects and pharmacological considerations of prescribing liraglutide and semaglutide in people with HIV.

RESULTS

Clinical experience is limited to two clinical cases of diabetic people with HIV using liraglutide after which a successful weight loss and glycaemic control were observed. None of the adverse events associated with liraglutide and semaglutide usage indicate an additional risk for people with HIV. Extra caution showed be warranted when initiating GLP-1 agonist therapy in people with HIV taking protease inhibitors who have pre-existing risk factors for heart rate variability to reduce the incidence of RP interval prolongation. GLP-1 agonists are metabolized by endopeptidases, and thus do not generate major drug-drug interactions with most drugs, including ARVs. GLP-s agonists are known to inhibit gastric acid secretion, which warrants caution and close monitoring when combined with atazanavir and oral rilpivirine, two ARVs that require low gastric pH for an optimal absorption.

CONCLUSION

Theoretical considerations and a few available clinical observations support semaglutide and liraglutide prescription in people with HIV, with, thus far, no indications of concern regarding efficacy, safety or pharmacological interactions with ARVs.

摘要

背景与目的

接受抗逆转录病毒药物(ARV)治疗的艾滋病毒感染者中,肥胖趋势和代谢紊乱正在上升。目前正在研究其根本原因和预防策略。两种胰高血糖素样肽 1(GLP-1)激动剂,利拉鲁肽和司美格鲁肽,以前被批准为降血糖药物,最近也被批准用于肥胖人群的长期减肥。由于缺乏针对艾滋病毒感染者的治疗指南或临床试验,我们讨论了在艾滋病毒感染者中开处方利拉鲁肽和司美格鲁肽的潜在益处、安全性方面和药理学考虑因素。

结果

临床经验仅限于两名使用利拉鲁肽的艾滋病毒合并糖尿病患者的临床案例,随后观察到体重减轻和血糖控制成功。与使用利拉鲁肽和司美格鲁肽相关的不良反应均未表明艾滋病毒感染者存在额外风险。在开始 GLP-1 激动剂治疗时,对于已经存在心率变异性风险因素的接受蛋白酶抑制剂治疗的艾滋病毒感染者,应格外小心,以降低 RP 间期延长的发生率。GLP-1 激动剂被内肽酶代谢,因此与大多数药物(包括 ARV)不会产生主要的药物相互作用。GLP-1 激动剂已知会抑制胃酸分泌,因此与阿扎那韦和口服利匹韦林联合使用时需要谨慎,并密切监测,这两种 ARV 需要低胃 pH 值才能达到最佳吸收。

结论

理论考虑和一些现有的临床观察支持在艾滋病毒感染者中使用司美格鲁肽和利拉鲁肽,迄今为止,没有关于疗效、安全性或与 ARV 相互作用的担忧的迹象。

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