Hiruma Shigenori, Shigiyama Fumika, Hisatake Shinji, Mizumura Sunao, Shiraga Nobuyuki, Hori Masaaki, Ikeda Takanori, Hirose Takahisa, Kumashiro Naoki
Division of Diabetes, Metabolism and Endocrinology, Department of Medicine, Toho University Graduate School of Medicine, 6-11-1 Omori-Nishi, Ota-ku, Tokyo, Japan.
Division of Cardiovascular Medicine, Department of Internal Medicine, Toho University Graduate School of Medicine, 6-11-1 Omori-Nishi, Ota-ku, Tokyo, Japan.
Cardiovasc Diabetol. 2021 Feb 2;20(1):32. doi: 10.1186/s12933-021-01228-3.
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, I-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/m). 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.
UMIN000026340; registered on February 28, 2017. https://upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000030257.
虽然钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂对心血管疾病（CVD）患者的心脏保护作用已得到证实，但其在疾病早期阶段相对于其他抗糖尿病药物的优势仍不明确。我们比较了SGLT2抑制剂恩格列净与二肽基肽酶-4（DPP-4）抑制剂西格列汀对心脏脂肪堆积、心脏功能和心脏代谢的心脏保护作用，重点关注无CVD并发症的早期2型糖尿病（T2DM）患者。
这是一项前瞻性、随机、开放标签、盲终点、平行组试验，纳入了44例日本T2DM患者。患者被随机分配接受为期12周的恩格列净或西格列汀治疗。分别通过磁共振成像和质子磁共振波谱评估心包脂肪堆积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、I-β-甲基碘苯基十五烷酸心肌闪烁显像和实验室检查。
患者为中年（50.3±10.7岁，平均值±标准差）且超重（体重指数29.3±4.9kg/m²）。他们的糖尿病病程较短（3.5±3.2年），糖化血红蛋白水平为7.1±0.8%，心脏功能保留（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病例外无血管并发症。12周治疗后，两组在心包、心外膜和心包旁脂肪含量变化、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与基线相比均未观察到差异。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）显著升高，而尿酸、血糖、血浆胰岛素和胰岛素抵抗稳态模型评估值显著低于西格列汀组（p<0.05）。
虽然两组对心脏脂肪和功能的影响在统计学上无差异，但恩格列净对尿酸、高密度脂蛋白胆固醇、酮体和胰岛素敏感性等心脏代谢生物标志物表现出更优的作用。因此，在考虑CVD的一级预防策略时，即使对于无当前CVD并发症的早期T2DM患者，早期补充SGLT2抑制剂可能比DPP-4抑制剂更有益。
UMIN000026340；于2017年2月28日注册。https://upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000030257。
