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胰高血糖素样肽-1受体激动剂在糖尿病肝移植受者中的应用:血糖控制及心脏代谢危险因素的变化

Glucagon-like peptide-1 receptor agonists in liver transplant recipients with diabetes: changes in glucose control and cardiometabolic risk factors.

作者信息

Grancini Valeria, Cogliati Irene, Alicandro Gianfranco, Oliverio Andreina, Di Benedetto Clara, Gaglio Alessia, Lampertico Pietro, Resi Veronica, Orsi Emanuela

机构信息

Fondazione Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) Ca' Granda Ospedale Maggiore Policlinico, Endocrinology Unit, Milan, Italy.

Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.

出版信息

Front Endocrinol (Lausanne). 2025 May 27;16:1586941. doi: 10.3389/fendo.2025.1586941. eCollection 2025.

Abstract

INTRODUCTION

Data about efficacy and safety of GLP1 receptor agonists in liver-transplanted patients are lacking.

METHODS

Among a population of liver-transplanted individuals with diabetes, we evaluated 68 patients before, 6, 12 and 18 months after starting a GLP1RA-based therapy, as add on to metformin or insulin. We assessed glycemic control, body weight and composition (with bio-impedance analysis), liver fibrosis and steatosis (with transient elastography). Amylase, lipase levels and concomitant therapies were recorded at basal and follow up evaluations. Patients had an e-mail contact to report any adverse events.

RESULTS

We observed a significant decrease in fasting plasma glucose, HbA1c, weight, BMI, waist circumference. We demonstrated a reduction in total and LDL cholesterol. Liver stiffness decreased during the first 6 months. The rate of adverse events was low and the symptoms reported didn't require any medical measures: 26.9% reported mild nausea, only 3 patients (7.69%) discontinued the drug dose due to gastrointestinal intolerance. No pancreatitis episodes were detected, amylase and lipase levels didn't increase (despite concomitant calcineurin inhibitors). No adjustments in immunosuppressant therapy were reported. Among the 45 patients requiring insulin when a GLP1RA therapy was added on, 20 (33.2%) and 31 (45.5%) could suspend insulin therapy at, respectively, 6 and 18 months.

DISCUSSION

In conclusion, GLP1RA-based therapy can be considered safe and effective in a short-term follow up in liver-transplanted patients. Further studies are needed to assess the effects of this drugs on long term complications, such as renal impairment, cardiovascular events and all-cause mortality.

摘要

引言

目前缺乏关于胰高血糖素样肽-1(GLP1)受体激动剂在肝移植患者中的疗效和安全性数据。

方法

在一组肝移植糖尿病患者中,我们对68例患者在开始基于GLP1受体激动剂(GLP1RA)的治疗前、治疗后6个月、12个月和18个月进行了评估,该治疗作为二甲双胍或胰岛素的补充治疗。我们评估了血糖控制、体重和身体成分(通过生物电阻抗分析)、肝纤维化和脂肪变性(通过瞬时弹性成像)。在基线和随访评估时记录淀粉酶、脂肪酶水平及联合治疗情况。患者通过电子邮件联系以报告任何不良事件。

结果

我们观察到空腹血糖、糖化血红蛋白(HbA1c)、体重、体重指数(BMI)、腰围显著降低。我们证明总胆固醇和低密度脂蛋白胆固醇有所下降。肝硬度在最初6个月内降低。不良事件发生率较低,报告的症状不需要任何医疗措施:26.9%报告有轻度恶心,只有3例患者(7.69%)因胃肠道不耐受而停药。未检测到胰腺炎发作,淀粉酶和脂肪酶水平未升高(尽管同时使用钙调神经磷酸酶抑制剂)。未报告免疫抑制治疗的调整情况。在开始GLP1RA治疗时需要胰岛素治疗的45例患者中,分别有20例(33.2%)和31例(45.5%)在6个月和18个月时可以停用胰岛素治疗。

讨论

总之,在肝移植患者的短期随访中,基于GLP1RA的治疗可被认为是安全有效的。需要进一步研究来评估这种药物对长期并发症的影响,如肾功能损害、心血管事件和全因死亡率。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/039b/12148859/2f0b6c217712/fendo-16-1586941-g001.jpg

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