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Differences in lipid metabolism between anagliptin and sitagliptin in patients with type 2 diabetes on statin therapy: a secondary analysis of the REASON trial.
Cardiovascular Diabetology ( IF 8.5 ) Pub Date : 2019-11-16 , DOI: 10.1186/s12933-019-0965-3
Atsuko Chihara 1 , Atsushi Tanaka 1 , Takeshi Morimoto 2 , Mio Sakuma 2 , Michio Shimabukuro 3 , Takashi Nomiyama 4 , Osamu Arasaki 5 , Shinichiro Ueda 6 , Koichi Node 1
Affiliation  

BACKGROUND Anagliptin, a dipeptidyl peptidase-4 inhibitor, is reported to reduce the level of low-density lipoprotein cholesterol (LDL-C). The underlying mechanism of this effect and effect on lipid metabolism however remains uncertain. AIM AND METHODS We therefore evaluate the effects of anagliptin on lipid metabolism-related markers compared with those of sitagliptin. The study was a secondary analysis using data obtained from the Randomized Evaluation of Anagliptin versus Sitagliptin On low-density lipoproteiN cholesterol in diabetes (REASON) trial. This trial in patients with type 2 diabetes at a high risk of cardiovascular events and on statin therapy showed that anagliptin reduced LDL-C levels to a greater extent than sitagliptin. Cholesterol absorption (campesterol and sitosterol) and synthesis (lathosterol) markers were measured at baseline and 52 weeks in the study cohort (n = 353). RESULTS There was no significant difference in the changes of campesterol or sitosterol between the two treatment groups (p = 0.85 and 0.55, respectively). Lathosterol concentration was increased significantly at 52 weeks with sitagliptin treatment (baseline, 1.2 ± 0.7 μg/mL vs. 52 weeks, 1.4 ± 1.0 μg/mL, p = 0.02), whereas it did not change in the anagliptin group (baseline, 1.3 ± 0.8 μg/mL vs. 52 weeks, 1.3 ± 0.7 μg/mL, p = 0.99). The difference in absolute change between the two groups showed a borderline significance (p = 0.06). CONCLUSION These findings suggest that anagliptin reduces LDL-C level by suppressing excess cholesterol synthesis, even in combination with statin therapy. Trial registration ClinicalTrials.gov number NCT02330406. https://clinicaltrials.gov/ct2/show/NCT02330406; registered January 5, 2015.

中文翻译:

他汀类药物治疗的2型糖尿病患者Anagliptin和Sitagliptin之间的脂质代谢差异:REASON试验的二级分析。

背景技术据报道,Anagliptin是一种二肽基肽酶4抑制剂,可降低低密度脂蛋白胆固醇(LDL-C)的水平。然而,这种作用和对脂质代谢的作用的潜在机制仍然不确定。目的和方法因此,与西他列汀相比,我们评估了Anagliptin对脂质代谢相关标志物的作用。该研究是使用从Anagliptin与Sitagliptin进行的关于低密度脂蛋白胆固醇在糖尿病中的随机评估(REASON)试验获得的数据进行的二次分析。这项针对患有心血管事件高风险和接受他汀类药物治疗的2型糖尿病患者的试验显示,Anagliptin较Leta-Catin更能降低LDL-C水平。在研究队列(n = 353)中,在基线和52周时测量了胆固醇吸收(菜油甾醇和谷甾醇)和合成(lathosterol)标志物。结果在两个治疗组之间,菜油甾醇或谷固醇的变化无显着差异(分别为p = 0.85和0.55)。西他列汀治疗后52周时,谷固醇浓度显着增加(基线为1.2±0.7μg/ mL,而52周为1.4±1.0μg/ mL,p = 0.02),而那格列汀组则无变化(基线为1.3) ±0.8μg/ mL,而52周为1.3±0.7μg/ mL,p = 0.99)。两组之间绝对变化的差异显示出临界值(p = 0.06)。结论这些发现表明,即使与他汀类药物联合使用,anagliptin仍可通过抑制过多的胆固醇合成来降低LDL-C水平。试用注册ClinicalTrials.gov编号NCT02330406。https://clinicaltrials.gov/ct2/show/NCT02330406; 于2015年1月5日注册。
更新日期:2019-11-16
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