Shigiyama Fumika, Hiruma Shigenori, Hisatake Shinji, Shiraga Nobuyuki, 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, Department of Medicine, Toho University Graduate School of Medicine, 6-11-1 Omori-Nishi, Ota-ku, Tokyo, Japan.
Diabetes Ther. 2019 Aug;10(4):1509-1521. doi: 10.1007/s13300-019-0640-4. Epub 2019 Jun 6.
Ectopic fat accumulation has been found to play a pathophysiological role in insulin resistance, type 2 diabetes (T2DM), and coronary artery diseases. Findings from a number of previous studies suggest that sodium glucose cotransporter 2 (SGLT2) inhibitors reduce lipid accumulation, including myocardial and pericardial fat, while dipeptidyl peptidase 4 (DPP4) inhibitors suppress ectopic lipid accumulation and improve cardiac function. However, a clinical study that precisely explains and compares the efficacy of SGLT2 inhibitors and DPP4 inhibitors on cardiac fat accumulation has not been performed. Moreover, the association between cardiac fat accumulation and cardiac function or metabolic changes, such as tissue-specific insulin resistance, remains unclear. It is our intention to conduct the first study to assess the effects of empagliflozin compared to sitagliptin in reducing ectopic fat accumulation, specifically pericardial fat, and its association with improvement in cardiac function and tissue-specific insulin sensitivity.
We have designed a prospective, randomized open-label, and blinded-endpoint study with the intention to enroll 44 Japanese patients with T2DM. The patients are to be divided them into two groups, an empagliflozin group and an sitagliptin group, with the former to be supplemented with empagliflozin 10 mg and the latter to be supplemented with sitagliptin 100 mg, both groups for 12 weeks. The primary endpoint of the study is the change in the amount of pericardial fat. The secondary endpoints are the changes in the amount of intracellular fat in the myocardium, cardiac function, tissue-specific insulin sensitivity, fatty acid metabolism in myocardial tissue, assessed by parameters of iodine-123-β-methyl-iodophenyl pentadecanoic acid myocardial scintigraphy, blood and urine biomarkers, and lifestyle evaluation.
The results of this study will be available in 2020. The aim of this study is to provide an effective treatment strategy for patients with T2DM by considering cardiac fat accumulation, cardiac function, and insulin resistance.
Boehringer Ingelheim & Eli Lilly and Company Diabetes Alliance.
University Hospital Medical Information Network Clinical Trial Registry: UMIN000026340.
异位脂肪堆积已被发现在胰岛素抵抗、2型糖尿病（T2DM）和冠状动脉疾病中发挥病理生理作用。此前多项研究结果表明，钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂可减少脂质堆积，包括心肌和心包脂肪，而二肽基肽酶4（DPP4）抑制剂可抑制异位脂质堆积并改善心脏功能。然而，尚未开展一项能精确解释和比较SGLT2抑制剂与DPP4抑制剂对心脏脂肪堆积疗效的临床研究。此外，心脏脂肪堆积与心脏功能或代谢变化（如组织特异性胰岛素抵抗）之间的关联仍不明确。我们打算开展第一项研究，评估恩格列净与西格列汀相比在减少异位脂肪堆积（特别是心包脂肪）方面的效果，以及其与心脏功能改善和组织特异性胰岛素敏感性的关联。
我们设计了一项前瞻性、随机开放标签且终点设盲的研究，计划纳入44例日本T2DM患者。患者将被分为两组，恩格列净组和西格列汀组，前者服用10 mg恩格列净，后者服用100 mg西格列汀，两组均治疗12周。该研究的主要终点是心包脂肪量的变化。次要终点包括心肌细胞内脂肪量的变化、心脏功能、组织特异性胰岛素敏感性、通过碘-123-β-甲基碘苯基十五烷酸心肌闪烁显像参数评估的心肌组织脂肪酸代谢、血液和尿液生物标志物以及生活方式评估。
本研究结果将于2020年公布。本研究的目的是通过考虑心脏脂肪堆积、心脏功能和胰岛素抵抗，为T2DM患者提供有效的治疗策略。
勃林格殷格翰公司与礼来公司糖尿病联盟。
大学医院医学信息网络临床试验注册中心：UMIN000026340。
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