Baseline ALT levels as a marker of glycemic response to treatment with GLP-1 receptor agonists

Jose A. Gimeno-Orna , Guayente Verdes-Sanz , Laura Borau-Maorad , Julia Campos-Fernández , Beatriz Lardiés-Sánchez , Marta Monreal-Villanueva , on behalf of the Aragonese Society of Endocrinology and Nutrition (SADEN)
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Abstract

Background and objectives

This study aimed to assess if ALT levels, as a marker of non-alcoholic fatty liver disease, may predict HbA1c response to treatment with GLP-1 receptor agonists (GLP-1 RAs).

Patients and methods

A retrospective, longitudinal, analytical study was conducted including patients with type 2 diabetes mellitus continuously treated with GLP-1 agonists (85% with liraglutide) for one year. Patients were divided into two groups according to baseline ALT levels, with 24 U/L (the median of the distribution) as the cut-off point. The dependent variable was HbA1c change (one-year follow-up minus baseline).

The predictive value of ALT levels above 24 U/L and ALT change was analyzed using multivariate linear regression adjusted to age, gender, diabetes duration, type and dose of GLP-1 RA, baseline HbA1c, baseline body mass index (BMI), and change in BMI.

Results

A total of 117 patients (48% females) aged 58.6 (SD 9.6) years were enrolled into the study. Treatment was associated with a change in ALT of −4.3 U/L (p = 0.041) and a change in HbA1c of −1.1% (p < 0.0001). Decreases in HbA1c (−1.41% vs −0.76%; p = 0.045) and ALT (−9.25 vs 0.46 U/L; p = 0.002) were significantly higher in patients with ALT levels above the median. In the multivariate analysis, both ALT >24 U/L (b = −0.74; 95% CI: −1.31 to −0.18; p = 0.011) and ALT change (b = 0.028; 95% CI: 0.010–0.046; p = 0.003), were significant response predictors.

Conclusions

Elevated baseline transaminase values and decreased transaminase levels during follow-up are associated to a favorable glycemic response to GLP-1 RAs.

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基线ALT水平作为GLP-1受体激动剂治疗后血糖反应的标志
背景和目的本研究旨在评估ALT水平作为非酒精性脂肪肝的标志物,是否可以预测GLP-1受体激动剂(GLP-1 RA)治疗后的HbA1c反应。患者和方法进行了一项回顾性、纵向、分析性研究,包括连续使用GLP-1激动剂(85%使用利拉鲁肽)治疗一年的2型糖尿病患者。根据基线ALT水平将患者分为两组,以24 U/L(分布的中位数)为分界点。因变量为HbA1c变化(一年随访减去基线)。使用多变量线性回归分析ALT水平高于24U/L和ALT变化的预测值,并根据年龄、性别、糖尿病持续时间、GLP-1 RA的类型和剂量、基线HbA1c、基线体重指数(BMI)和BMI变化进行调整。结果共有117名患者(48%为女性),年龄58.6岁(标准差9.6)。治疗与ALT变化−4.3 U/L(p=0.041)和HbA1c变化−1.1%(p<;0.0001)相关。ALT水平高于中位数的患者,HbA1c下降(−1.41%vs−0.76%;p=0.045)和ALT下降(−9.25 vs 0.46 U/L;p=0.002)明显更高。在多变量分析中,ALT>;24 U/L(b=−0.74;95%置信区间:−1.31至−0.18;p=0.011)和ALT变化(b=0.028;95%可信区间:0.010–0.046;p=0.003)是显著的反应预测因子。结论随访期间基线转氨酶值的升高和转氨酶水平的降低与GLP-1 RAs的良好血糖反应有关。
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