1.Study Design and Protocol for a Randomized Controlled Trial of Enavogliflozin to Evaluate Cardiorenal Outcomes in Type 2 Diabetes (ENVELOP)
Nam Hoon KIM ; Soo LIM ; In-Kyung JEONG ; Eun-Jung RHEE ; Jun Sung MOON ; Ohk-Hyun RYU ; Hyuk-Sang KWON ; Jong Chul WON ; Sang Soo KIM ; Sang Yong KIM ; Bon Jeong KU ; Heung Yong JIN ; Sin Gon KIM ; Bong-Soo CHA ;
Diabetes & Metabolism Journal 2025;49(2):225-234
Background:
The novel sodium-glucose cotransporter-2 (SGLT2) inhibitor enavogliflozin effectively lowers glycosylated hemoglobin levels and body weights without the increased risk of serious adverse events; however, the long-term clinical benefits of enavogliflozin in terms of cardiovascular and renal outcomes have not been investigated.
Methods:
This study is an investigator-initiated, multicenter, randomized, pragmatic, open-label, active-controlled, non-inferiority trial. Eligible participants are adults (aged ≥19 years) with type 2 diabetes mellitus (T2DM) who have a history of, or are at risk of, cardiovascular disease. A total of 2,862 participants will be randomly assigned to receive either enavogliflozin or other SGLT2 inhibitors with proven cardiorenal benefits, such as dapagliflozin or empagliflozin. The primary endpoint is the time to the first occurrence of a composite of major adverse cardiovascular or renal events (Clinical Research Information Service registration number: KCT0009243).
Conclusion
This trial will determine whether enavogliflozin is non-inferior to dapagliflozin or empagliflozin in terms of cardiorenal outcomes in patients with T2DM and cardiovascular risk factors. This study will elucidate the role of enavogliflozin in preventing vascular complications in patients with T2DM.
2.Study Design and Protocol for a Randomized Controlled Trial of Enavogliflozin to Evaluate Cardiorenal Outcomes in Type 2 Diabetes (ENVELOP)
Nam Hoon KIM ; Soo LIM ; In-Kyung JEONG ; Eun-Jung RHEE ; Jun Sung MOON ; Ohk-Hyun RYU ; Hyuk-Sang KWON ; Jong Chul WON ; Sang Soo KIM ; Sang Yong KIM ; Bon Jeong KU ; Heung Yong JIN ; Sin Gon KIM ; Bong-Soo CHA ;
Diabetes & Metabolism Journal 2025;49(2):225-234
Background:
The novel sodium-glucose cotransporter-2 (SGLT2) inhibitor enavogliflozin effectively lowers glycosylated hemoglobin levels and body weights without the increased risk of serious adverse events; however, the long-term clinical benefits of enavogliflozin in terms of cardiovascular and renal outcomes have not been investigated.
Methods:
This study is an investigator-initiated, multicenter, randomized, pragmatic, open-label, active-controlled, non-inferiority trial. Eligible participants are adults (aged ≥19 years) with type 2 diabetes mellitus (T2DM) who have a history of, or are at risk of, cardiovascular disease. A total of 2,862 participants will be randomly assigned to receive either enavogliflozin or other SGLT2 inhibitors with proven cardiorenal benefits, such as dapagliflozin or empagliflozin. The primary endpoint is the time to the first occurrence of a composite of major adverse cardiovascular or renal events (Clinical Research Information Service registration number: KCT0009243).
Conclusion
This trial will determine whether enavogliflozin is non-inferior to dapagliflozin or empagliflozin in terms of cardiorenal outcomes in patients with T2DM and cardiovascular risk factors. This study will elucidate the role of enavogliflozin in preventing vascular complications in patients with T2DM.
3.Study Design and Protocol for a Randomized Controlled Trial of Enavogliflozin to Evaluate Cardiorenal Outcomes in Type 2 Diabetes (ENVELOP)
Nam Hoon KIM ; Soo LIM ; In-Kyung JEONG ; Eun-Jung RHEE ; Jun Sung MOON ; Ohk-Hyun RYU ; Hyuk-Sang KWON ; Jong Chul WON ; Sang Soo KIM ; Sang Yong KIM ; Bon Jeong KU ; Heung Yong JIN ; Sin Gon KIM ; Bong-Soo CHA ;
Diabetes & Metabolism Journal 2025;49(2):225-234
Background:
The novel sodium-glucose cotransporter-2 (SGLT2) inhibitor enavogliflozin effectively lowers glycosylated hemoglobin levels and body weights without the increased risk of serious adverse events; however, the long-term clinical benefits of enavogliflozin in terms of cardiovascular and renal outcomes have not been investigated.
Methods:
This study is an investigator-initiated, multicenter, randomized, pragmatic, open-label, active-controlled, non-inferiority trial. Eligible participants are adults (aged ≥19 years) with type 2 diabetes mellitus (T2DM) who have a history of, or are at risk of, cardiovascular disease. A total of 2,862 participants will be randomly assigned to receive either enavogliflozin or other SGLT2 inhibitors with proven cardiorenal benefits, such as dapagliflozin or empagliflozin. The primary endpoint is the time to the first occurrence of a composite of major adverse cardiovascular or renal events (Clinical Research Information Service registration number: KCT0009243).
Conclusion
This trial will determine whether enavogliflozin is non-inferior to dapagliflozin or empagliflozin in terms of cardiorenal outcomes in patients with T2DM and cardiovascular risk factors. This study will elucidate the role of enavogliflozin in preventing vascular complications in patients with T2DM.
4.Study Design and Protocol for a Randomized Controlled Trial of Enavogliflozin to Evaluate Cardiorenal Outcomes in Type 2 Diabetes (ENVELOP)
Nam Hoon KIM ; Soo LIM ; In-Kyung JEONG ; Eun-Jung RHEE ; Jun Sung MOON ; Ohk-Hyun RYU ; Hyuk-Sang KWON ; Jong Chul WON ; Sang Soo KIM ; Sang Yong KIM ; Bon Jeong KU ; Heung Yong JIN ; Sin Gon KIM ; Bong-Soo CHA ;
Diabetes & Metabolism Journal 2025;49(2):225-234
Background:
The novel sodium-glucose cotransporter-2 (SGLT2) inhibitor enavogliflozin effectively lowers glycosylated hemoglobin levels and body weights without the increased risk of serious adverse events; however, the long-term clinical benefits of enavogliflozin in terms of cardiovascular and renal outcomes have not been investigated.
Methods:
This study is an investigator-initiated, multicenter, randomized, pragmatic, open-label, active-controlled, non-inferiority trial. Eligible participants are adults (aged ≥19 years) with type 2 diabetes mellitus (T2DM) who have a history of, or are at risk of, cardiovascular disease. A total of 2,862 participants will be randomly assigned to receive either enavogliflozin or other SGLT2 inhibitors with proven cardiorenal benefits, such as dapagliflozin or empagliflozin. The primary endpoint is the time to the first occurrence of a composite of major adverse cardiovascular or renal events (Clinical Research Information Service registration number: KCT0009243).
Conclusion
This trial will determine whether enavogliflozin is non-inferior to dapagliflozin or empagliflozin in terms of cardiorenal outcomes in patients with T2DM and cardiovascular risk factors. This study will elucidate the role of enavogliflozin in preventing vascular complications in patients with T2DM.
5.Breast Cancer Statistics in Korea, 2021
Chihwan David CHA ; Chan Sub PARK ; Hee-Chul SHIN ; Jaihong HAN ; Jung Eun CHOI ; Joo Heung KIM ; Kyu-Won JUNG ; Sae Byul LEE ; Sang Eun NAM ; Tae In YOON ; Young-Joon KANG ; Zisun KIM ; So-Youn JUNG ; Hyun-Ah KIM ;
Journal of Breast Cancer 2024;27(6):351-361
The Korean Breast Cancer Society (KBCS) has collected nationwide registry data on clinicopathologic characteristics and treatment since 1996. This study aimed to analyze the clinical characteristics of breast cancer in Korea and assess changes in breast cancer statistics for 2021 using data from the KBCS registry and the Korean Central Cancer Registry. In 2021, 34,628 women were newly diagnosed with breast cancer. The median age of women diagnosed with breast cancer was 53.4 years, with the highest incidence occurring in the 40–49 age group. The most common molecular subtype was hormone receptor-positive and human epidermal growth factor receptor 2 (HER2)-negative, accounting for 69.1% of cases, while HER2-positive subtypes comprised 19.3%. During the coronavirus disease 2019 pandemic, the national breast cancer screening rate declined. However, the incidence of early-stage breast cancer (stages 0 and I) continued to increase, accounting for 65.6% of newly diagnosed cases in 2021. Our results showed that the overall survival rate for patients with breast cancer has improved, primarily due to a rise in early-stage diagnoses and advancements in treatment.
6.Breast Cancer Statistics in Korea, 2021
Chihwan David CHA ; Chan Sub PARK ; Hee-Chul SHIN ; Jaihong HAN ; Jung Eun CHOI ; Joo Heung KIM ; Kyu-Won JUNG ; Sae Byul LEE ; Sang Eun NAM ; Tae In YOON ; Young-Joon KANG ; Zisun KIM ; So-Youn JUNG ; Hyun-Ah KIM ;
Journal of Breast Cancer 2024;27(6):351-361
The Korean Breast Cancer Society (KBCS) has collected nationwide registry data on clinicopathologic characteristics and treatment since 1996. This study aimed to analyze the clinical characteristics of breast cancer in Korea and assess changes in breast cancer statistics for 2021 using data from the KBCS registry and the Korean Central Cancer Registry. In 2021, 34,628 women were newly diagnosed with breast cancer. The median age of women diagnosed with breast cancer was 53.4 years, with the highest incidence occurring in the 40–49 age group. The most common molecular subtype was hormone receptor-positive and human epidermal growth factor receptor 2 (HER2)-negative, accounting for 69.1% of cases, while HER2-positive subtypes comprised 19.3%. During the coronavirus disease 2019 pandemic, the national breast cancer screening rate declined. However, the incidence of early-stage breast cancer (stages 0 and I) continued to increase, accounting for 65.6% of newly diagnosed cases in 2021. Our results showed that the overall survival rate for patients with breast cancer has improved, primarily due to a rise in early-stage diagnoses and advancements in treatment.
7.Breast Cancer Statistics in Korea, 2021
Chihwan David CHA ; Chan Sub PARK ; Hee-Chul SHIN ; Jaihong HAN ; Jung Eun CHOI ; Joo Heung KIM ; Kyu-Won JUNG ; Sae Byul LEE ; Sang Eun NAM ; Tae In YOON ; Young-Joon KANG ; Zisun KIM ; So-Youn JUNG ; Hyun-Ah KIM ;
Journal of Breast Cancer 2024;27(6):351-361
The Korean Breast Cancer Society (KBCS) has collected nationwide registry data on clinicopathologic characteristics and treatment since 1996. This study aimed to analyze the clinical characteristics of breast cancer in Korea and assess changes in breast cancer statistics for 2021 using data from the KBCS registry and the Korean Central Cancer Registry. In 2021, 34,628 women were newly diagnosed with breast cancer. The median age of women diagnosed with breast cancer was 53.4 years, with the highest incidence occurring in the 40–49 age group. The most common molecular subtype was hormone receptor-positive and human epidermal growth factor receptor 2 (HER2)-negative, accounting for 69.1% of cases, while HER2-positive subtypes comprised 19.3%. During the coronavirus disease 2019 pandemic, the national breast cancer screening rate declined. However, the incidence of early-stage breast cancer (stages 0 and I) continued to increase, accounting for 65.6% of newly diagnosed cases in 2021. Our results showed that the overall survival rate for patients with breast cancer has improved, primarily due to a rise in early-stage diagnoses and advancements in treatment.
8.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
Endocrinology and Metabolism 2024;39(5):722-731
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.
9.Novel Genome-Wide Interactions Mediated via BOLL and EDNRA Polymorphisms in Intracranial Aneurysm
Eun Pyo HONG ; Dong Hyuk YOUN ; Bong Jun KIM ; Jae Jun LEE ; Sehyeon NAM ; Hyojong YOO ; Heung Cheol KIM ; Jong Kook RHIM ; Jeong Jin PARK ; Jin Pyeong JEON
Journal of Korean Neurosurgical Society 2023;66(4):409-417
Objective:
: The association between boule (BOLL) and endothelin receptor type A (EDNRA) loci and intracranial aneurysm (IA) formation has been reported via genome-wide association studies. We sought to identify genome-wide interactions involving BOLL and EDNRA loci for IA in a Korean adult cohort.
Methods:
: Genome-wide pairwise interaction analyses of BOLL and EDNRA involving 250 patients with IA and 296 controls were performed using the additive effect model after adjusting for confounding factors.
Results:
: Among 512575 single-nucleotide polymorphisms (SNPs), 23 and 11 common SNPs suggested a genome-wide interaction threshold (p<1.25×10-8) involving rs700651 (BOLL) and rs6841581 (EDNRA). Rather than singe SNP effect of BOLL or EDNRA on IA development, they showed a synergistic effect on IA formation via multifactorial pair-wise interactions. The rs1105980 of PTCH1 gene showed the most significant interaction with rs700651 (natural log-transformed odds ratio [lnOR], 1.53; p=6.41×10-11). The rs74585958 of RYK gene interacted strongly with rs6841581 (lnOR, -19.91; p=1.64×10-9). Although, there was no direct interaction between BOLL and EDNRA variants, two EDNRA-interacting gene variants of TNIK (rs11925024 and rs1231) and FTO (rs9302654), and one BOLL-interacting METTL4 gene variant (rs549315) exhibited marginal interaction with BOLL gene.
Conclusion
: BOLL or EDNRA may have a synergistic effect on IA formation via multifactorial pair-wise interactions.
10.Efficacy of the Ketogenic Diet for Pediatric Epilepsy According to the Presence of Detectable Somatic mTOR Pathway Mutations in the Brain
Ara KO ; Nam Suk SIM ; Han Som CHOI ; Donghwa YANG ; Se Hee KIM ; Joon Soo LEE ; Dong Seok KIM ; Jeong Ho LEE ; Heung Dong KIM ; Hoon-Chul KANG
Journal of Clinical Neurology 2022;18(1):71-78
Background:
and Purpose A multifactorial antiepileptic mechanism underlies the ketogenic diet (KD), and one of the proposed mechanisms of action is that the KD inhibits the mammalian target of rapamycin (mTOR) pathway. To test this clinically, this study aimed to determine the efficacy of the KD in patients with pathologically confirmed focal cortical dysplasia (FCD) due to genetically identifiable mTOR pathway dysregulation.
Methods:
A cohort of patients with pathologically confirmed FCD after epilepsy surgery and who were screened for the presence of germline and somatic mutations related to the mTOR pathway in peripheral blood and resected brain tissue was constructed prospectively. A retrospective review of the efficacy of the prior KD in these patients was performed.
Results:
Twenty-five patients with pathologically confirmed FCD and who were screened for the presence of detectable somatic mTOR pathway mutations had received a sufficient KD. Twelve of these patients (48.0%) had germline or somatic detectable mTOR pathway mutations. A response was defined as a ≥50% reduction in seizure frequency. The efficacy of the KD after 3 months of dietary therapy was superior in patients with detectable mTOR pathway mutations than in patients without detectable mTOR pathway mutations, although the difference was not statistically significant (responder rates of 58.3% vs. 38.5%, p=0.434).
Conclusions
A greater proportion of patients with mTOR pathway responded to the KD, but there was no statistically significant difference in efficacy of the KD between patients with and without detectable mTOR pathway mutations. Further study is warranted due to the smallness of the sample and the limited number of mTOR pathway genes tested in this study.

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