Endocrinology and Metabolism (Oct 2024)
Study Design and Protocol for a Randomized Controlled Trial to Assess Long-Term Efficacy and Safety of a Triple Combination of Ezetimibe, Fenofibrate, and Moderate-Intensity Statin in Patients with Type 2 Diabetes and Modifiable Cardiovascular Risk Factors (ENSEMBLE)
- Nam Hoon Kim,
- Juneyoung Lee,
- Suk Chon,
- Jae Myung Yu,
- In-Kyung Jeong,
- Soo Lim,
- Won Jun Kim,
- Keeho Song,
- Ho Chan Cho,
- Hea Min Yu,
- Kyoung-Ah Kim,
- Sang Soo Kim,
- Soon Hee Lee,
- Chong Hwa Kim,
- Soo Heon Kwak,
- Yong‐ho Lee,
- Choon Hee Chung,
- Sihoon Lee,
- Heung Yong Jin,
- Jae Hyuk Lee,
- Gwanpyo Koh,
- Sang-Yong Kim,
- Jaetaek Kim,
- Ju Hee Lee,
- Tae Nyun Kim,
- Hyun Jeong Jeon,
- Ji Hyun Lee,
- Jae-Han Jeon,
- Hye Jin Yoo,
- Hee Kyung Kim,
- Hyeong-Kyu Park,
- Il Seong Nam-Goong,
- Seongbin Hong,
- Chul Woo Ahn,
- Ji Hee Yu,
- Jong Heon Park,
- Keun-Gyu Park,
- Chan Ho Park,
- Kyong Hye Joung,
- Ohk-Hyun Ryu,
- Keun Yong Park,
- Eun-Gyoung Hong,
- Bong-Soo Cha,
- Kyu Chang Won,
- Yoon-Sok Chung,
- Sin Gon Kim
Affiliations
- Nam Hoon Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea
- Juneyoung Lee
- Department of Biostatistics, Korea University College of Medicine, Seoul, Korea
- Suk Chon
- Department of Endocrinology and Metabolism, Kyung Hee University Hospital, College of Medicine, Kyung Hee University, Seoul, Korea
- Jae Myung Yu
- Department of Internal Medicine, Hallym University Kangnam Sacred Heart Hospital, College of Medicine, Hallym University, Seoul, Korea
- In-Kyung Jeong
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Kyung Hee University Hospital at Gangdong, College of Medicine, Kyung Hee University, Seoul, Korea
- Soo Lim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
- Won Jun Kim
- Division of Endocrinology, Department of Internal Medicine, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung, Korea
- Keeho Song
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea
- Ho Chan Cho
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
- Hea Min Yu
- Department of Internal Medicine, Daejeon Eulji Medical Center, Eulji University, Daejeon, Korea
- Kyoung-Ah Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Dongguk University Ilsan Hospital, Goyang, Korea
- Sang Soo Kim
- Department of Internal Medicine, Pusan National University Hospital, Busan, Korea
- Soon Hee Lee
- Department of Internal Medicine, Inje University Busan Paik Hospital, Inje University College of Medicine, Busan, Korea
- Chong Hwa Kim
- Department of Internal Medicine, Bucheon Sejong Hospital, Bucheon, Korea
- Soo Heon Kwak
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
- Yong‐ho Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Choon Hee Chung
- Department of Internal Medicine, Research Institute of Metabolism and Inflammation, Yonsei University Wonju College of Medicine, Wonju, Korea
- Sihoon Lee
- Department of Internal Medicine, Gachon University College of Medicine, Incheon, Korea
- Heung Yong Jin
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Research Institute of Clinical Medicine of Jeonbuk National University Medical School-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, Korea
- Jae Hyuk Lee
- Division of Endocrinology, Department of Internal Medicine, Myongji Hospital, Goyang, Korea
- Gwanpyo Koh
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Jeju National University College of Medicine, Jeju, Korea
- Sang-Yong Kim
- Division of Endocrinology and Metabolism, Chosun University College of Medicine, Gwangju, Korea
- Jaetaek Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
- Ju Hee Lee
- Department of Internal Medicine, Chungnam National University College of Medicine, Daejeon, Korea
- Tae Nyun Kim
- Department of Internal Medicine, Inje University College of Medicine, Busan, Korea
- Hyun Jeong Jeon
- Department of Endocrinology, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheongju, Korea
- Ji Hyun Lee
- Department of Internal Medicine, Daegu Catholic University School of Medicine, Daegu, Korea
- Jae-Han Jeon
- Department of Internal Medicine, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University, Daegu, Korea
- Hye Jin Yoo
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea
- Hee Kyung Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea
- Hyeong-Kyu Park
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Soonchunhyang University Seoul Hospital, Soonchunhyang University College of Medicine, Seoul, Korea
- Il Seong Nam-Goong
- Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea
- Seongbin Hong
- Department of Endocrinology and Metabolism, Inha University College of Medicine, Incheon, Korea
- Chul Woo Ahn
- Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
- Ji Hee Yu
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Korea
- Jong Heon Park
- Big Data Steering Department, National Health Insurance Service, Wonju, Korea
- Keun-Gyu Park
- Department of Internal Medicine, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, Daegu, Korea
- Chan Ho Park
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Dong-A University Medical Center, Dong-A University College of Medicine, Busan, Korea
- Kyong Hye Joung
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Chungnam National University College of Medicine, Daejeon, Korea
- Ohk-Hyun Ryu
- Division of Endocrinology and Metabolism, College of Medicine, Hallym University, Chuncheon, Korea
- Keun Yong Park
- Department of Endocrinology and Metabolism, Konyang University Hospital, Konyang University College of Medicine, Daejeon, Korea
- Eun-Gyoung Hong
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Hallym University Dongtan Sacred Heart Hospital, Hwaseong, Korea
- Bong-Soo Cha
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Kyu Chang Won
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea
- Yoon-Sok Chung
- Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon, Korea
- Sin Gon Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea
- DOI
- https://doi.org/10.3803/EnM.2024.1995
- Journal volume & issue
-
Vol. 39,
no. 5
pp. 722 – 731
Abstract
Background Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator-activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined. Methods This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months. Conclusion This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D.
Keywords
