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.Circadian Rhythms, Depressive and Anxiety Symptoms, and Chronotype: Interaction and Implication for Mental Health in Healthy Subjects
Jung Won YOU ; Yoonyoung NAM ; Rina YU ; Vin RYU
Mood and Emotion 2024;22(1):10-18
Background:
Circadian rhythms have gained importance in the field of psychiatry because of their involvement in overall body functions and their association with mental health. This study investigated the relationship between circadian rhythms, depressive symptoms, anxiety symptoms, and chronotype.
Methods:
Circadian rhythms, depression and anxiety symptoms, hypomanic symptoms, quality of life, hopelessness, and chronotype were evaluated in 30 healthy adults.
Results:
Multiple linear regression analysis revealed statistically significant correlations between Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN) scores and certain factors. Particularly, Quick Inventory of Depressive Symptomatology (p=0.009), Beck Anxiety Inventory (p=0.03), and Morningness-Eveningness Questionnaire (p<0.001) were found to be significant predictors of the degree of circadian rhythm disruption, as measured by BRIAN. The results showed that irregularity in circadian rhythms was associated with depression and anxiety symptoms, and no significant correlation was observed between chronotype and irregularity in the circadian rhythms. The findings indicated that misalignment between an individual’s chronotype and societal norms, such as work schedules and meal times, could contribute to circadian rhythm disruption, particularly in individuals with an evening chronotype. In contrast, this disruption was associated with an increased risk of anxiety and depression.
Conclusion
These findings provide important information to better understand the impact of circadian rhythms on mental health.
6.Growth and Developmental Outcomes of Triplets Preterm Infants according to the Chorionicity: A Retrospective Cohort Study
Eun Woo NAM ; Jae Hui RYU ; Hye Su HWANG ; Ho Jung CHOI ; Seulgi PARK ; Seung Han SHIN ; Ee-Kyung KIM ; Han-Suk KIM
Perinatology 2024;35(2):61-68
Objective:
We elucidated the effect of monochorionicity on neonatal and long-term neurologic outcomes on an individual basis in triplets.
Methods:
We retrospectively reviewed the perinatal outcomes and development and growth at 18 to 24 months corrected age (CA) of triplets born alive between 24 and 32 weeks of gestational age (GA) between 2009 and 2021 from the Seoul National University Hospital database. Neurodevelopmental impairment (NDI) was defined as any delay among the Bayley-III domains (motor and language), cerebral palsy, hearing impairment, or visual loss and was performed at a CA of 18 to 24 months.
Results:
We included 40 sets of triplets (120 infants), comprising 26, 10, and 4 sets of trichorionic (TC), dichorionic (DC), and monochorionic (MC) triplets, respectively. Ten infants, unaffected by monochorionicity out of 30 DC infants, were included in the non-MC group. Eighty-eight infants were included in the non-MC group, and 32 infants were affected by monochorionicity. In vitro fertilization-embryo transfer was more frequent in the non-MC group (P<0.05), and twin-to-twin transfusion syndrome affected only the MC group (P<0.01). At 24 months of CA, a combined delay of language and cognition in Bayley-III was evident in the MC group (P<0.05). Although NDI did not significantly differ between the 2 groups (P=0.059), the composite outcome of NDI+ postnatal death was significantly different (P<0.05). NDI+ postnatal death correlated with GA, Z-score of birth weight, brain injury, and monochorionicity in the univariate analysis (P<0.05). Multivariate analysis revealed a significant correlation between monochorionicity and NDI+ postnatal death. (P<0.05).
Conclusion
Monochorionicity is associated with adverse long-term neurodevelopmental out comes.
7.Circadian Rhythms, Depressive and Anxiety Symptoms, and Chronotype: Interaction and Implication for Mental Health in Healthy Subjects
Jung Won YOU ; Yoonyoung NAM ; Rina YU ; Vin RYU
Mood and Emotion 2024;22(1):10-18
Background:
Circadian rhythms have gained importance in the field of psychiatry because of their involvement in overall body functions and their association with mental health. This study investigated the relationship between circadian rhythms, depressive symptoms, anxiety symptoms, and chronotype.
Methods:
Circadian rhythms, depression and anxiety symptoms, hypomanic symptoms, quality of life, hopelessness, and chronotype were evaluated in 30 healthy adults.
Results:
Multiple linear regression analysis revealed statistically significant correlations between Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN) scores and certain factors. Particularly, Quick Inventory of Depressive Symptomatology (p=0.009), Beck Anxiety Inventory (p=0.03), and Morningness-Eveningness Questionnaire (p<0.001) were found to be significant predictors of the degree of circadian rhythm disruption, as measured by BRIAN. The results showed that irregularity in circadian rhythms was associated with depression and anxiety symptoms, and no significant correlation was observed between chronotype and irregularity in the circadian rhythms. The findings indicated that misalignment between an individual’s chronotype and societal norms, such as work schedules and meal times, could contribute to circadian rhythm disruption, particularly in individuals with an evening chronotype. In contrast, this disruption was associated with an increased risk of anxiety and depression.
Conclusion
These findings provide important information to better understand the impact of circadian rhythms on mental health.
8.Growth and Developmental Outcomes of Triplets Preterm Infants according to the Chorionicity: A Retrospective Cohort Study
Eun Woo NAM ; Jae Hui RYU ; Hye Su HWANG ; Ho Jung CHOI ; Seulgi PARK ; Seung Han SHIN ; Ee-Kyung KIM ; Han-Suk KIM
Perinatology 2024;35(2):61-68
Objective:
We elucidated the effect of monochorionicity on neonatal and long-term neurologic outcomes on an individual basis in triplets.
Methods:
We retrospectively reviewed the perinatal outcomes and development and growth at 18 to 24 months corrected age (CA) of triplets born alive between 24 and 32 weeks of gestational age (GA) between 2009 and 2021 from the Seoul National University Hospital database. Neurodevelopmental impairment (NDI) was defined as any delay among the Bayley-III domains (motor and language), cerebral palsy, hearing impairment, or visual loss and was performed at a CA of 18 to 24 months.
Results:
We included 40 sets of triplets (120 infants), comprising 26, 10, and 4 sets of trichorionic (TC), dichorionic (DC), and monochorionic (MC) triplets, respectively. Ten infants, unaffected by monochorionicity out of 30 DC infants, were included in the non-MC group. Eighty-eight infants were included in the non-MC group, and 32 infants were affected by monochorionicity. In vitro fertilization-embryo transfer was more frequent in the non-MC group (P<0.05), and twin-to-twin transfusion syndrome affected only the MC group (P<0.01). At 24 months of CA, a combined delay of language and cognition in Bayley-III was evident in the MC group (P<0.05). Although NDI did not significantly differ between the 2 groups (P=0.059), the composite outcome of NDI+ postnatal death was significantly different (P<0.05). NDI+ postnatal death correlated with GA, Z-score of birth weight, brain injury, and monochorionicity in the univariate analysis (P<0.05). Multivariate analysis revealed a significant correlation between monochorionicity and NDI+ postnatal death. (P<0.05).
Conclusion
Monochorionicity is associated with adverse long-term neurodevelopmental out comes.
9.Circadian Rhythms, Depressive and Anxiety Symptoms, and Chronotype: Interaction and Implication for Mental Health in Healthy Subjects
Jung Won YOU ; Yoonyoung NAM ; Rina YU ; Vin RYU
Mood and Emotion 2024;22(1):10-18
Background:
Circadian rhythms have gained importance in the field of psychiatry because of their involvement in overall body functions and their association with mental health. This study investigated the relationship between circadian rhythms, depressive symptoms, anxiety symptoms, and chronotype.
Methods:
Circadian rhythms, depression and anxiety symptoms, hypomanic symptoms, quality of life, hopelessness, and chronotype were evaluated in 30 healthy adults.
Results:
Multiple linear regression analysis revealed statistically significant correlations between Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN) scores and certain factors. Particularly, Quick Inventory of Depressive Symptomatology (p=0.009), Beck Anxiety Inventory (p=0.03), and Morningness-Eveningness Questionnaire (p<0.001) were found to be significant predictors of the degree of circadian rhythm disruption, as measured by BRIAN. The results showed that irregularity in circadian rhythms was associated with depression and anxiety symptoms, and no significant correlation was observed between chronotype and irregularity in the circadian rhythms. The findings indicated that misalignment between an individual’s chronotype and societal norms, such as work schedules and meal times, could contribute to circadian rhythm disruption, particularly in individuals with an evening chronotype. In contrast, this disruption was associated with an increased risk of anxiety and depression.
Conclusion
These findings provide important information to better understand the impact of circadian rhythms on mental health.
10.Growth and Developmental Outcomes of Triplets Preterm Infants according to the Chorionicity: A Retrospective Cohort Study
Eun Woo NAM ; Jae Hui RYU ; Hye Su HWANG ; Ho Jung CHOI ; Seulgi PARK ; Seung Han SHIN ; Ee-Kyung KIM ; Han-Suk KIM
Perinatology 2024;35(2):61-68
Objective:
We elucidated the effect of monochorionicity on neonatal and long-term neurologic outcomes on an individual basis in triplets.
Methods:
We retrospectively reviewed the perinatal outcomes and development and growth at 18 to 24 months corrected age (CA) of triplets born alive between 24 and 32 weeks of gestational age (GA) between 2009 and 2021 from the Seoul National University Hospital database. Neurodevelopmental impairment (NDI) was defined as any delay among the Bayley-III domains (motor and language), cerebral palsy, hearing impairment, or visual loss and was performed at a CA of 18 to 24 months.
Results:
We included 40 sets of triplets (120 infants), comprising 26, 10, and 4 sets of trichorionic (TC), dichorionic (DC), and monochorionic (MC) triplets, respectively. Ten infants, unaffected by monochorionicity out of 30 DC infants, were included in the non-MC group. Eighty-eight infants were included in the non-MC group, and 32 infants were affected by monochorionicity. In vitro fertilization-embryo transfer was more frequent in the non-MC group (P<0.05), and twin-to-twin transfusion syndrome affected only the MC group (P<0.01). At 24 months of CA, a combined delay of language and cognition in Bayley-III was evident in the MC group (P<0.05). Although NDI did not significantly differ between the 2 groups (P=0.059), the composite outcome of NDI+ postnatal death was significantly different (P<0.05). NDI+ postnatal death correlated with GA, Z-score of birth weight, brain injury, and monochorionicity in the univariate analysis (P<0.05). Multivariate analysis revealed a significant correlation between monochorionicity and NDI+ postnatal death. (P<0.05).
Conclusion
Monochorionicity is associated with adverse long-term neurodevelopmental out comes.

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