A prospective randomized study comparing effects of empagliflozin to sitagliptin on cardiac fat accumulation, cardiac function, and cardiac metabolism in patients with early-stage type 2 diabetes: the ASSET study.
A prospective randomized study comparing effects of empagliflozin to sitagliptin on cardiac fat accumulation, cardiac function, and cardiac metabolism in patients with early-stage type 2 diabetes: the ASSET study.
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一项比较恩格列净与西格列汀对早期2型糖尿病患者心脏脂肪蓄积、心脏功能和心脏代谢影响的前瞻性随机研究：ASSET研究
DOI：
10.1186/s12933-021-01228-3
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发表时间：
2021-02-02
影响因子：
9.3
通讯作者：
Kumashiro N
中科院分区：
文献类型：
--
作者：
Hiruma S;Shigiyama F;Hisatake S;Mizumura S;Shiraga N;Hori M;Ikeda T;Hirose T;Kumashiro N
虽然钠-葡萄糖协同转运蛋白-2（SGLT 2）抑制剂在心血管疾病（CVD）患者中的心脏保护作用已得到证实，但其在早期阶段相对于其他抗糖尿病药物的优势仍不清楚。我们比较了恩格列净（一种SGLT 2抑制剂）与西格列汀（一种二肽基肽酶-4（DPP-4）抑制剂）的心脏保护作用，重点关注无CVD并发症的早期2型糖尿病（T2 DM）患者的心脏脂肪蓄积、心脏功能和心脏代谢。这是一项前瞻性、随机化、开放标签、设盲终点、平行组试验，入组了44例日本T2 DM患者。患者随机接受恩格列净或西格列汀12周给药。分别通过磁共振成像和质子磁共振波谱评估心包脂肪积聚和心肌甘油三酯含量。在基线和12周治疗期后进行超声心动图、123 I-β-甲基-碘苯基十五烷酸心肌造影和实验室检查。患者为中年（50.3 ± 10.7岁，平均值±标准差）和超重（体重指数29.3 ± 4.9 kg/m2）。他们的糖尿病病程较短（3.5 ± 3.2年），HbA 1c水平为7.1 ± 0.8%，心脏功能正常（射血分数73.8 ± 5.0%），除各有1例基线糖尿病肾病和外周动脉疾病外，无血管并发症。12周治疗后，在心包、心外膜和心旁脂肪含量、心肌甘油三酯含量、心脏功能和质量以及心脏脂肪酸代谢方面，未观察到两组之间较基线的差异。然而，考虑到心脏代谢生物标志物，恩格列净组的高密度脂蛋白胆固醇和酮体（包括β-羟基丁酸）显著增加，而尿酸、血糖、血浆胰岛素和胰岛素抵抗的稳态模型评估显著低于西格列汀组（p < 0.05）。尽管两组之间对心脏脂肪和功能的影响无统计学差异，但恩格列净对心脏代谢生物标志物（如尿酸、高密度脂蛋白胆固醇、酮体和胰岛素敏感性）的影响具有上级优势。因此，在考虑CVD的一级预防策略时，早期补充SGLT 2抑制剂可能比DPP-4抑制剂更有益，即使在目前无CVD并发症的早期T2 DM患者中也是如此。临床试验注册：UMIN 000026340;注册日期：2017年2月28日。https://upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?接收号= R 000030257
While the cardioprotective benefits of sodium-glucose cotransporter-2 (SGLT2) inhibitors have been established in patients with cardiovascular disease (CVD), their advantages over other anti-diabetic drugs at earlier stages remain unclear. We compared the cardioprotective effects of empagliflozin, an SGLT2 inhibitor, with those of sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, focusing on cardiac fat accumulation, cardiac function, and cardiac metabolism in patients with early-stage type 2 diabetes mellitus (T2DM) without CVD complications. This was a prospective, randomized, open-label, blinded-endpoint, parallel-group trial that enrolled 44 Japanese patients with T2DM. The patients were randomized for 12-week administration of empagliflozin or sitagliptin. Pericardial fat accumulation and myocardial triglyceride content were evaluated by magnetic resonance imaging and proton magnetic resonance spectroscopy, respectively. Echocardiography, 123I-β-methyl-iodophenyl pentadecanoic acid myocardial scintigraphy, and laboratory tests were performed at baseline and after the 12-week treatment period. The patients were middle-aged (50.3 ± 10.7 years, mean ± standard deviation) and overweight (body mass index 29.3 ± 4.9 kg/m2). They had a short diabetes duration (3.5 ± 3.2 years), HbA1c levels of 7.1 ± 0.8%, and preserved cardiac function (ejection fraction 73.8 ± 5.0%) with no vascular complications, except for one baseline case each of diabetic nephropathy and peripheral arterial disease. After the 12-week treatment, no differences from baseline were observed between the two groups regarding changes in pericardial, epicardial, and paracardial fat content; myocardial triglyceride content; cardiac function and mass; and cardiac fatty acid metabolism. However, considering cardiometabolic biomarkers, high-density lipoprotein cholesterol and ketone bodies, including β-hydroxybutyric acid, were significantly increased, whereas uric acid, plasma glucose, plasma insulin, and homeostasis model assessment of insulin resistance were significantly lower in the empagliflozin group than in the sitagliptin group (p < 0.05). Although the effects on cardiac fat and function were not statistically different between the two groups, empagliflozin exhibited superior effects on cardiometabolic biomarkers, such as uric acid, high-density lipoprotein cholesterol, ketone bodies, and insulin sensitivity. Therefore, when considering the primary preventive strategies for CVD, early supplementation with SGLT2 inhibitors may be more beneficial than DPP-4 inhibitors, even in patients with early-stage T2DM without current CVD complications. Clinical Trial Registration: UMIN000026340; registered on February 28, 2017. https://upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000030257
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影响因子：
9.3
作者：
Bouchi R;Terashima M;Sasahara Y;Asakawa M;Fukuda T;Takeuchi T;Nakano Y;Murakami M;Minami I;Izumiyama H;Hashimoto K;Yoshimoto T;Ogawa Y
通讯作者：
Ogawa Y
影响因子：
158.5
作者：
Holman, Rury R.;Paul, Sanjoy K.;Neil, H. Andrew W.
通讯作者：
Neil, H. Andrew W.
影响因子：
7.1
作者：
Ding, Jingzhong;Hsu, Fang-Chi;Carr, J. Jeffrey
通讯作者：
Carr, J. Jeffrey
影响因子：
9.3
作者：
Kim, Kyoung Jin;Choi, Jimi;Kim, Nam Hoon
通讯作者：
Kim, Nam Hoon
影响因子：
4.6
作者：
Hsu, Jung-Chi;Wang, Chih-Yuan;Yang, Wei-Shiung
通讯作者：
Yang, Wei-Shiung