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Efficacy and Safety of Evogliptin Add-on Therapy to Dapagliflozin/Metformin Combinations in Patients with Poorly Controlled Type 2 Diabetes Mellitus: A 24-Week Multicenter Randomized Placebo-Controlled Parallel-Design Phase-3 Trial with a 28-Week Extension
Jun Sung Moon, Il Rae Park, Hae Jin Kim, Choon Hee Chung, Kyu Chang Won, Kyung Ah Han, Cheol-Young Park, Jong Chul Won, Dong Jun Kim, Gwan Pyo Koh, Eun Sook Kim, Jae Myung Yu, Eun-Gyoung Hong, Chang Beom Lee, Kun-Ho Yoon
Diabetes Metab J. 2023;47(6):808-817.   Published online September 26, 2023
DOI: https://doi.org/10.4093/dmj.2022.0387
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  • 1 Web of Science
  • 1 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
This study investigates the long-term efficacy and safety of evogliptin add-on therapy in patients with inadequately controlled type 2 diabetes mellitus (T2DM) previously received dapagliflozin and metformin (DAPA/MET) combination.
Methods
In this multicenter randomized placebo-controlled phase 3 trial, patients with glycosylated hemoglobin (HbA1c) levels 7.0% to 10.5% (n=283) previously used DAPA 10 mg plus MET (≥1,000 mg) were randomly assigned to the evogliptin 5 mg once daily or placebo group (1:1). The primary endpoint was the difference in the HbA1c level from baseline at week 24, and exploratory endpoints included the efficacy and safety of evogliptin over 52 weeks (trial registration: ClinicalTrials.gov NCT04170998).
Results
Evogliptin add-on to DAPA/MET therapy was superior in HbA1c reduction compared to placebo at weeks 24 and 52 (least square [LS] mean difference, –0.65% and –0.55%; 95% confidence interval [CI], –0.79 to –0.51 and –0.71 to –0.39; P<0.0001). The proportion of patients achieving HbA1c <7% was higher in the triple combination group at week 52 (32.14% vs. 8.51% in placebo; odds ratio, 5.62; P<0.0001). Evogliptin significantly reduced the fasting glucose levels and mean daily glucose levels with improvement in homeostatic model assessment of β-cell function (LS mean difference, 9.04; 95% CI, 1.86 to 16.21; P=0.0138). Adverse events were similar between the groups, and no serious adverse drug reactions were reported in the evogliptin group.
Conclusion
Long-term triple combination with evogliptin added to DAPA/MET showed superior HbA1c reduction and glycemic control compared to placebo at 52 weeks and was well tolerated.

Citations

Citations to this article as recorded by  
  • Efficacy and safety of dapagliflozin add‐on to evogliptin plus metformin therapy in patients with type 2 diabetes: A randomized, double‐blind, placebo‐controlled study
    In‐Kyung Jeong, Kyung Mook Choi, Kyung Ah Han, Kyoung‐Ah Kim, In Joo Kim, Seung Jin Han, Won Young Lee, Soon Jib Yoo
    Diabetes, Obesity and Metabolism.2024;[Epub]     CrossRef
Basic Research
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Altered Metabolic Phenotypes and Hypothalamic Neuronal Activity Triggered by Sodium-Glucose Cotransporter 2 Inhibition
Ho Gyun Lee, Il Hyeon Jung, Byong Seo Park, Hye Rim Yang, Kwang Kon Kim, Thai Hien Tu, Jung-Yong Yeh, Sewon Lee, Sunggu Yang, Byung Ju Lee, Jae Geun Kim, Il Seong Nam-Goong
Diabetes Metab J. 2023;47(6):784-795.   Published online August 23, 2023
DOI: https://doi.org/10.4093/dmj.2022.0261
  • 2,294 View
  • 171 Download
  • 2 Web of Science
  • 2 Crossref
AbstractAbstract PDFPubReader   ePub   
Background
Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are currently used to treat patients with diabetes. Previous studies have demonstrated that treatment with SGLT-2 inhibitors is accompanied by altered metabolic phenotypes. However, it has not been investigated whether the hypothalamic circuit participates in the development of the compensatory metabolic phenotypes triggered by the treatment with SGLT-2 inhibitors.
Methods
Mice were fed a standard diet or high-fat diet and treated with dapagliflozin, an SGLT-2 inhibitor. Food intake and energy expenditure were observed using indirect calorimetry system. The activity of hypothalamic neurons in response to dapagliflozin treatment was evaluated by immunohistochemistry with c-Fos antibody. Quantitative real-time polymerase chain reaction was performed to determine gene expression patterns in the hypothalamus of dapagliflozin-treated mice.
Results
Dapagliflozin-treated mice displayed enhanced food intake and reduced energy expenditure. Altered neuronal activities were observed in multiple hypothalamic nuclei in association with appetite regulation. Additionally, we found elevated immunosignals of agouti-related peptide neurons in the paraventricular nucleus of the hypothalamus.
Conclusion
This study suggests the functional involvement of the hypothalamus in the development of the compensatory metabolic phenotypes induced by SGLT-2 inhibitor treatment.

Citations

Citations to this article as recorded by  
  • Altered Metabolic Phenotypes and Hypothalamic Neuronal Activity Triggered by Sodium-Glucose Cotransporter 2 Inhibition (Diabetes Metab J 2023;47:784-95)
    Jae Hyun Bae
    Diabetes & Metabolism Journal.2024; 48(1): 157.     CrossRef
  • Altered Metabolic Phenotypes and Hypothalamic Neuronal Activity Triggered by Sodium-Glucose Cotransporter 2 Inhibition (Diabetes Metab J 2023;47:784-95)
    Ho Gyun Lee, Il Hyeon Jung, Byong Seo Park, Hye Rim Yang, Kwang Kon Kim, Thai Hien Tu, Jung-Yong Yeh, Sewon Lee, Sunggu Yang, Byung Ju Lee, Jae Geun Kim, Il Seong Nam-Goong
    Diabetes & Metabolism Journal.2024; 48(1): 159.     CrossRef
Drug Regimen
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Efficacy and Safety of Enavogliflozin versus Dapagliflozin as Add-on to Metformin in Patients with Type 2 Diabetes Mellitus: A 24-Week, Double-Blind, Randomized Trial
Kyung Ah Han, Yong Hyun Kim, Doo Man Kim, Byung Wan Lee, Suk Chon, Tae Seo Sohn, In Kyung Jeong, Eun-Gyoung Hong, Jang Won Son, Jae Jin Nah, Hwa Rang Song, Seong In Cho, Seung-Ah Cho, Kun Ho Yoon
Diabetes Metab J. 2023;47(6):796-807.   Published online February 9, 2023
DOI: https://doi.org/10.4093/dmj.2022.0315
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  • 639 Download
  • 7 Web of Science
  • 8 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Enavogliflozin is a novel sodium-glucose cotransporter-2 inhibitor currently under clinical development. This study evaluated the efficacy and safety of enavogliflozin as an add-on to metformin in Korean patients with type 2 diabetes mellitus (T2DM) against dapagliflozin.
Methods
In this multicenter, double-blind, randomized, phase 3 study, 200 patients were randomized to receive enavogliflozin 0.3 mg/day (n=101) or dapagliflozin 10 mg/day (n=99) in addition to ongoing metformin therapy for 24 weeks. The primary objective of the study was to prove the non-inferiority of enavogliflozin to dapagliflozin in glycosylated hemoglobin (HbA1c) change at week 24 (non-inferiority margin of 0.35%) (Clinical trial registration number: NCT04634500).
Results
Adjusted mean change of HbA1c at week 24 was –0.80% with enavogliflozin and –0.75% with dapagliflozin (difference, –0.04%; 95% confidence interval, –0.21% to 0.12%). Percentages of patients achieving HbA1c <7.0% were 61% and 62%, respectively. Adjusted mean change of fasting plasma glucose at week 24 was –32.53 and –29.14 mg/dL. An increase in urine glucose-creatinine ratio (60.48 vs. 44.94, P<0.0001) and decrease in homeostasis model assessment of insulin resistance (–1.85 vs. –1.31, P=0.0041) were significantly greater with enavogliflozin than dapagliflozin at week 24. Beneficial effects of enavogliflozin on body weight (–3.77 kg vs. –3.58 kg) and blood pressure (systolic/diastolic, –5.93/–5.41 mm Hg vs. –6.57/–4.26 mm Hg) were comparable with those of dapagliflozin, and both drugs were safe and well-tolerated.
Conclusion
Enavogliflozin added to metformin significantly improved glycemic control in patients with T2DM and was non-inferior to dapagliflozin 10 mg, suggesting enavogliflozin as a viable treatment option for patients with inadequate glycemic control on metformin alone.

Citations

Citations to this article as recorded by  
  • Efficacy and safety of enavogliflozin vs. dapagliflozin as add-on therapy in patients with type 2 diabetes mellitus based on renal function: a pooled analysis of two randomized controlled trials
    Young Sang Lyu, Sangmo Hong, Si Eun Lee, Bo Young Cho, Cheol-Young Park
    Cardiovascular Diabetology.2024;[Epub]     CrossRef
  • A 52‐week efficacy and safety study of enavogliflozin versus dapagliflozin as an add‐on to metformin in patients with type 2 diabetes mellitus: ENHANCE‐M extension study
    Tae Seo Sohn, Kyung‐Ah Han, Yonghyun Kim, Byung‐Wan Lee, Suk Chon, In‐Kyung Jeong, Eun‐Gyoung Hong, Jang Won Son, JaeJin Na, Jae Min Cho, Seong In Cho, Wan Huh, Kun‐Ho Yoon
    Diabetes, Obesity and Metabolism.2024; 26(6): 2248.     CrossRef
  • The effect of renal function on the pharmacokinetics and pharmacodynamics of enavogliflozin, a potent and selective sodium‐glucose cotransporter‐2 inhibitor, in type 2 diabetes
    Sae Im Jeong, Mu Seong Ban, Jun‐Gi Hwang, Min‐Kyu Park, Soo Lim, Sejoong Kim, Soon Kil Kwon, Yoonjin Kim, Jae Min Cho, Jae Jin Na, Wan Huh, Jae‐Yong Chung
    Diabetes, Obesity and Metabolism.2024; 26(7): 2588.     CrossRef
  • Long‐term efficacy and safety of enavogliflozin in Korean people with type 2 diabetes: A 52‐week extension of a Phase 3 randomized controlled trial
    Soo Heon Kwak, Kyung Ah Han, Eun Sook Kim, Sung Hee Choi, Jong Chul Won, Jae Myung Yu, Seungjoon Oh, Hye Jin Yoo, Chong Hwa Kim, Kyung‐Soo Kim, SungWan Chun, Yong Hyun Kim, Seung Ah Cho, Da Hye Kim, Kyong Soo Park
    Diabetes, Obesity and Metabolism.2024; 26(10): 4203.     CrossRef
  • Role of novel sodium glucose co-transporter-2 inhibitor enavogliflozin in type-2 diabetes: A systematic review and meta-analysis
    Deep Dutta, B.G. Harish, Beatrice Anne, Lakshmi Nagendra
    Diabetes & Metabolic Syndrome: Clinical Research & Reviews.2023; 17(8): 102816.     CrossRef
  • Characteristics of the Latest Therapeutic Agent for Diabetes
    Nuri Yun
    The Journal of Korean Diabetes.2023; 24(3): 148.     CrossRef
  • Prospects of using sodium-glucose co-transporter-2 (SGLT-2) inhibitors in patients with metabolic-associated fatty liver disease (MAFLD)
    Iryna Kostitska, Nadia Protas, Liliia Petrovska
    Diabetes Obesity Metabolic Syndrome.2023; (5): 8.     CrossRef
  • Navigating the Future of Diabetes Treatment with New Drugs: Focusing on the Possibilities and Prospects of Enavogliflozin
    Sang Youl Rhee
    Diabetes & Metabolism Journal.2023; 47(6): 769.     CrossRef
Short Communication
Drug/Regimen
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The Efficacy of Treatment Intensification by Quadruple Oral Therapy Compared to GLP-1RA Therapy in Poorly Controlled Type 2 Diabetes Mellitus Patients: A Real-World Data Study
Minyoung Kim, Hosu Kim, Kyong Young Kim, Soo Kyoung Kim, Junghwa Jung, Jong Ryeal Hahm, Jaehoon Jung, Jong Ha Baek
Diabetes Metab J. 2023;47(1):135-139.   Published online April 29, 2022
DOI: https://doi.org/10.4093/dmj.2021.0373
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
We compared the glycemic efficacy of treatment intensification between quadruple oral antidiabetic drug therapy and once-weekly glucagon-like peptide-1 receptor agonist (GLP-1RA)-based triple therapy in patients with poorly controlled type 2 diabetes mellitus refractory to triple oral therapy. For 24 weeks, changes in glycosylated hemoglobin (HbA1c) from baseline were compared between the two treatment groups. Of all 96 patients, 50 patients were treated with quadruple therapy, and 46 were treated with GLP-1RA therapy. Reductions in HbA1c for 24 weeks were comparable (in both, 1.1% reduction from baseline; P=0.59). Meanwhile, lower C-peptide level was associated with a lower glucose-lowering response of GLP-1RA therapy (R=0.3, P=0.04) but not with quadruple therapy (R=–0.13, P=0.40). HbA1c reduction by GLP-1RA therapy was inferior to that by quadruple therapy in the low C-peptide subgroup (mean, –0.1% vs. –1.3%; P=0.04). Treatment intensification by switching to quadruple oral therapy showed similar glucose-lowering efficacy to weekly GLP-1RA-based triple therapy. Meanwhile, the therapeutic response was affected by C-peptide levels in the GLP-1RA therapy group but not in the quadruple therapy group.
Original Articles
Drug/Regimen
Comparison of Serum Ketone Levels and Cardiometabolic Efficacy of Dapagliflozin versus Sitagliptin among Insulin-Treated Chinese Patients with Type 2 Diabetes Mellitus
Chi-Ho Lee, Mei-Zhen Wu, David Tak-Wai Lui, Darren Shing-Hei Chan, Carol Ho-Yi Fong, Sammy Wing-Ming Shiu, Ying Wong, Alan Chun-Hong Lee, Joanne King-Yan Lam, Yu-Cho Woo, Karen Siu-Ling Lam, Kelvin Kai-Hang Yiu, Kathryn Choon-Beng Tan
Diabetes Metab J. 2022;46(6):843-854.   Published online April 28, 2022
DOI: https://doi.org/10.4093/dmj.2021.0319
  • 6,154 View
  • 267 Download
  • 7 Web of Science
  • 7 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Insulin-treated patients with long duration of type 2 diabetes mellitus (T2DM) are at increased risk of ketoacidosis related to sodium-glucose co-transporter 2 inhibitor (SGLT2i). The extent of circulating ketone elevation in these patients remains unknown. We conducted this study to compare the serum ketone response between dapagliflozin, an SGLT2i, and sitagliptin, a dipeptidyl peptidase-4 inhibitor, among insulin-treated T2DM patients.
Methods
This was a randomized, open-label, active comparator-controlled study involving 60 insulin-treated T2DM patients. Participants were randomized 1:1 for 24-week of dapagliflozin 10 mg daily or sitagliptin 100 mg daily. Serum β-hydroxybutyrate (BHB) levels were measured at baseline, 12 and 24 weeks after intervention. Comprehensive cardiometabolic assessments were performed with measurements of high-density lipoprotein cholesterol (HDL-C) cholesterol efflux capacity (CEC), vibration-controlled transient elastography and echocardiography.
Results
Among these 60 insulin-treated participants (mean age 58.8 years, diabetes duration 18.2 years, glycosylated hemoglobin 8.87%), as compared with sitagliptin, serum BHB levels increased significantly after 24 weeks of dapagliflozin (P=0.045), with a median of 27% increase from baseline. Change in serum BHB levels correlated significantly with change in free fatty acid levels. Despite similar glucose lowering, dapagliflozin led to significant improvements in body weight (P=0.006), waist circumference (P=0.028), HDL-C (P=0.041), CEC (P=0.045), controlled attenuation parameter (P=0.007), and liver stiffness (P=0.022). Average E/e’, an echocardiographic index of left ventricular diastolic dysfunction, was also significantly lower at 24 weeks in participants treated with dapagliflozin (P=0.037).
Conclusion
Among insulin-treated T2DM patients with long diabetes duration, compared to sitagliptin, dapagliflozin modestly increased ketone levels and was associated with cardiometabolic benefits.

Citations

Citations to this article as recorded by  
  • Serum thrombospondin‐2 level changes with liver stiffness improvement in patients with type 2 diabetes
    Jimmy Ho Cheung Mak, David Tak‐Wai Lui, Carol Ho‐Yi Fong, Chloe Yu‐Yan Cheung, Ying Wong, Alan Chun‐Hong Lee, Ruby Lai‐Chong Hoo, Aimin Xu, Kathryn Choon‐Beng Tan, Karen Siu‐Ling Lam, Chi‐Ho Lee
    Clinical Endocrinology.2024; 100(3): 230.     CrossRef
  • SGLT-2 inhibitors as novel treatments of multiple organ fibrosis
    Junpei Hu, Jianhui Teng, Shan Hui, Lihui Liang
    Heliyon.2024; 10(8): e29486.     CrossRef
  • Innovations and applications of ketone body monitoring in diabetes care
    Naoki Sakane
    Diabetology International.2024; 15(3): 370.     CrossRef
  • Effect of dapagliflozin on readmission and loop diuretics use in patients with acute heart failure: a retrospective propensity score-matched cohort study
    Dong Wu, Zhen Ma, Xiaoying Wang, Xiaowu Wang, Xiaojuan Wang
    BMC Cardiovascular Disorders.2024;[Epub]     CrossRef
  • Effect of sodium-glucose cotransporter protein-2 inhibitors on left ventricular hypertrophy in patients with type 2 diabetes: A systematic review and meta-analysis
    Yao Wang, Yujie Zhong, Zhehao Zhang, Shuhao Yang, Qianying Zhang, Bingyang Chu, Xulin Hu
    Frontiers in Endocrinology.2023;[Epub]     CrossRef
  • Effects of SGLT2 inhibitors on hepatic fibrosis and steatosis: A systematic review and meta-analysis
    Peipei Zhou, Ying Tan, Zhenning Hao, Weilong Xu, Xiqiao Zhou, Jiangyi Yu
    Frontiers in Endocrinology.2023;[Epub]     CrossRef
  • The impact of sodium-glucose Cotransporter-2 inhibitors on lipid profile: A meta-analysis of 28 randomized controlled trials
    Gang Fan, Dian long Guo, Hong Zuo
    European Journal of Pharmacology.2023; 959: 176087.     CrossRef
Drug/Regimen
Article image
Effect of Dapagliflozin as an Add-on Therapy to Insulin on the Glycemic Variability in Subjects with Type 2 Diabetes Mellitus (DIVE): A Multicenter, Placebo-Controlled, Double-Blind, Randomized Study
Seung-Hwan Lee, Kyung-Wan Min, Byung-Wan Lee, In-Kyung Jeong, Soon-Jib Yoo, Hyuk-Sang Kwon, Yoon-Hee Choi, Kun-Ho Yoon
Diabetes Metab J. 2021;45(3):339-348.   Published online May 28, 2020
DOI: https://doi.org/10.4093/dmj.2019.0203
  • 9,223 View
  • 355 Download
  • 14 Web of Science
  • 17 Crossref
Graphical AbstractGraphical Abstract AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background

Glycemic variability is associated with the development of diabetic complications and hypoglycemia. However, the effect of sodium-glucose transporter 2 (SGLT2) inhibitors on glycemic variability is controversial. We aimed to examine the effect of dapagliflozin as an add-on therapy to insulin on the glycemic variability assessed using continuous glucose monitoring (CGM) in subjects with type 2 diabetes mellitus.

Methods

In this multicenter, placebo-controlled, double-blind, randomized study, 84 subjects received 10 mg of dapagliflozin (n=41) or the placebo (n=43) for 12 weeks. CGM was performed before and after treatment to compare the changes in glycemic variability measures (standard deviation [SD], mean amplitude of glycemic excursions [MAGEs]).

Results

At week 12, significant reductions in glycosylated hemoglobin (−0.74%±0.66% vs. 0.01%±0.65%, P<0.001), glycated albumin (−3.94%±2.55% vs. −0.67%±2.48%, P<0.001), and CGM-derived mean glucose (−41.6±39.2 mg/dL vs. 1.1±46.2 mg/dL, P<0.001) levels were observed in the dapagliflozin group compared with the placebo group. SD and MAGE were significantly decreased in the dapagliflozin group, but not in the placebo group. However, the difference in ΔSD and ΔMAGE failed to reach statistical significance between two groups. No significant differences in the incidence of safety endpoints were observed between the two groups.

Conclusion

Dapagliflozin effectively decreased glucose levels, but not glucose variability, after 12 weeks of treatment in participants with type 2 diabetes mellitus receiving insulin treatment. The role of SGLT2 inhibitors in glycemic variability warrants further investigations.

Citations

Citations to this article as recorded by  
  • Selective sodium-glucose cotransporter-2 inhibitors in the improvement of hemoglobin and hematocrit in patients with type 2 diabetes mellitus: a network meta-analysis
    Yuanyuan Luo, Ruojing Bai, Wei Zhang, Guijun Qin
    Frontiers in Endocrinology.2024;[Epub]     CrossRef
  • Continuous Glucose Monitoring Profiles and Health Outcomes After Dapagliflozin Plus Saxagliptin vs Insulin Glargine
    Donald C Simonson, Marcia A Testa, Ella Ekholm, Maxwell Su, Tina Vilsbøll, Serge A Jabbour, Marcus Lind
    The Journal of Clinical Endocrinology & Metabolism.2024;[Epub]     CrossRef
  • Impact of empagliflozin on insulin needs in patients with heart failure and diabetes: An EMPEROR‐Pooled analysis
    Khawaja M. Talha, Jennifer Green, Gerasimos Filippatos, Stuart Pocock, Faiez Zannad, Martina Brueckmann, Elke Schueler, Anne Pernille Ofstad, João Pedro Ferreira, Stefan D. Anker, Javed Butler, Julio Rosenstock, Milton Packer
    Diabetes, Obesity and Metabolism.2024; 26(7): 2578.     CrossRef
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    Pei-Ling Yu, You Yu, Shuang Li, Bai-Chen Mu, Ming-Hua Nan, Min Pang
    World Journal of Diabetes.2024; 15(7): 1518.     CrossRef
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    Yuyan Sun, Bing Lu, Yuanwen Hu, Yingqi Lv, Shao Zhong
    International Journal of General Medicine.2024; Volume 17: 4297.     CrossRef
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    Zhigui Zheng, Dongyuan He, Jianguo Chen, Xiaohui Xie, Yunan Lu, Binbin Wu, Xinxin Jiang
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    Yang Cao, Ning Liang, Ting Liu, Jingai Fang, Xiaodong Zhang
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    Juan Miguel Huertas Cañas, Maria Alejandra Gomez Gutierrez, Andres Bedoya Ossa
    European Endocrinology.2023; 19(2): 4.     CrossRef
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    Louis Monnier, Claude Colette, Fabrice Bonnet, David Owens
    Médecine des Maladies Métaboliques.2022; 16(1): 15.     CrossRef
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    Min Jeong Park, Kyung Mook Choi
    Diabetes & Metabolism Journal.2022; 46(1): 49.     CrossRef
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    Alicia Swee Yan Yip, Shariel Leong, Yao Hao Teo, Yao Neng Teo, Nicholas L. X. Syn, Ray Meng See, Caitlin Fern Wee, Elliot Yeung Chong, Chi-Hang Lee, Mark Y. Chan, Tiong-Cheng Yeo, Raymond C. C. Wong, Ping Chai, Ching-Hui Sia
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    SuA Oh, Sujata Purja, Hocheol Shin, Minji Kim, Eunyoung Kim
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    Yana Yu. Dzhun, Yevhen Yu. Marushko, Yanina A. Saienko, Nadiya M. Rudenko, Borys M. Mankovsky
    Ukrainian Journal of Cardiovascular Surgery.2022; 30(3): 35.     CrossRef
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    Alessandro Bellis, Ciro Mauro, Emanuele Barbato, Antonio Ceriello, Antonio Cittadini, Carmine Morisco
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    Heeyoung Lee, Se-eun Park, Eun-Young Kim
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    Menghui Luo, Xiaocen Kong, Huiying Wang, Xiaofang Zhai, Tingting Cai, Bo Ding, Yun Hu, Ting Jing, Xiaofei Su, Huiqin Li, Jianhua Ma, Yoshifumi Saisho
    Journal of Diabetes Research.2020; 2020: 1.     CrossRef
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    Jee Hee Yoo, Jae Hyeon Kim
    Diabetes & Metabolism Journal.2020; 44(6): 828.     CrossRef
Review
A Novel Therapeutic Agent for Type 2 Diabetes Mellitus: SGLT2 Inhibitor
Chang Hee Jung, Jung Eun Jang, Joong-Yeol Park
Diabetes Metab J. 2014;38(4):261-273.   Published online August 20, 2014
DOI: https://doi.org/10.4093/dmj.2014.38.4.261
  • 8,408 View
  • 160 Download
  • 64 Web of Science
  • 60 Crossref
AbstractAbstract PDFPubReader   

Type 2 diabetes mellitus (T2DM) is a complex endocrine and metabolic disorder, and a major public health problem that is rapidly increasing in prevalence. Although a wide range of pharmacotherapies for glycemic control is now available, management of T2DM remains complex and challenging. The kidneys contribute immensely to glucose homeostasis by reabsorbing glucose from the glomerular filtrate. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, a new class of antidiabetic agents that inhibit glucose absorption from the kidney independent of insulin, offer a unique opportunity to improve the outcomes of patients with T2DM. In this review, we provide an overview of two globally-approved SGLT2 inhibitors, dapagliflozin and canagliflozin, and discuss their effects and safety. This information will help clinicians to decide whether these drugs will benefit their patients.

Citations

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  • Clinical outcomes with the use of sodium-glucose cotransporter-2 inhibitors in patients with atrial fibrillation and type 2 diabetes mellitus: a multi-centre, real-world cohort study
    Jaehyuk Jang, Soyoon Park, Soohyun Kim, Sung-Hwan Kim, Yong-Seog Oh, Young Kyoung Sa, Youmi Hwang, Sung-Won Jang, Sang-Hyun Ihm, Young Choi
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    Mingdi Liu, Jichao Liu, Qiuhong Wang, Ping Song, Haichao Li, Zan Sun, Chenglong Shi, Weibing Dong
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  • Quantitative analysis of low content polymorphic impurities in canagliflozin tablets by PXRD, NIR, ATR-FITR and Raman solid-state analysis techniques combined with stoichiometry
    Mingdi Liu, Jichao Liu, Qiuhong Wang, Ping Song, Haichao Li, Songgu Wu, Junbo Gong
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    Bartosz Rolek, Mateusz Haber, Magdalena Gajewska, Sylwester Rogula, Arkadiusz Pietrasik, Aleksandra Gąsecka
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    Jun Sung Moon, Il Rae Park, Hae Jin Kim, Choon Hee Chung, Kyu Chang Won, Kyung Ah Han, Cheol-Young Park, Jong Chul Won, Dong Jun Kim, Gwan Pyo Koh, Eun Sook Kim, Jae Myung Yu, Eun-Gyoung Hong, Chang Beom Lee, Kun-Ho Yoon
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  • The fate of flavonoids after oral administration: a comprehensive overview of its bioavailability
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    Derun Taner Ertugrul, Erdal Kan, Cigdem Bahadir Tura, Haci Bayram Tugtekin, Hayati Ayakta, Mehmet Celebioglu, Ceren Yılmaz, Onur Utebay, Ilhan Yetkin, Eren Gurkan, Kerem Sezer, Ramazan Gen, Suleyman Ozcaylak, Yildiz Okuturlar, Mehmet Coskun, Nilgun Govec
    International Journal of Diabetes in Developing Countries.2022; 42(1): 147.     CrossRef
  • Sodium–glucose cotransporter 2 inhibitors do not increase the risk of fractures in real‐world clinical practice in Korea: A national observational cohort study
    Kyoung Hwa Ha, Dae Jung Kim, Yong Jun Choi
    Journal of Diabetes Investigation.2022; 13(6): 986.     CrossRef
  • Luseogliflozin preserves the pancreatic beta-cell mass and function in db/db mice by improving mitochondrial function
    Yuki Yamauchi, Akinobu Nakamura, Takashi Yokota, Kiyohiko Takahashi, Shinichiro Kawata, Kazuhisa Tsuchida, Kazuno Omori, Hiroshi Nomoto, Hiraku Kameda, Kyu Yong Cho, Toshihisa Anzai, Shinya Tanaka, Yasuo Terauchi, Hideaki Miyoshi, Tatsuya Atsumi
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  • Blood glucose levels and bodyweight change after dapagliflozin administration
    Hyunah Kim, Seung‐Hwan Lee, Hyunyong Lee, Hyeon Woo Yim, Jae‐Hyoung Cho, Kun‐Ho Yoon, Hun‐Sung Kim
    Journal of Diabetes Investigation.2021; 12(9): 1594.     CrossRef
  • Dapagliflozin Improves Cardiac Hemodynamics and Mitigates Arrhythmogenesis in Mitral Regurgitation‐Induced Myocardial Dysfunction
    Yu‐Wen Lin, Chin‐Yu Chen, Jhih‐Yuan Shih, Bor‐Chih Cheng, Ching‐Ping Chang, Mao‐Tsun Lin, Chung‐Han Ho, Zhih‐Cherng Chen, Sudeshna Fisch, Wei‐Ting Chang
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    Ja Young Jeon, Kyoung Hwa Ha, Dae Jung Kim
    Diabetes & Metabolism Journal.2021; 45(4): 505.     CrossRef
  • Ipragliflozin, an SGLT2 Inhibitor, Ameliorates High-Fat Diet-Induced Metabolic Changes by Upregulating Energy Expenditure through Activation of the AMPK/ SIRT1 Pathway
    Ji-Yeon Lee, Minyoung Lee, Ji Young Lee, Jaehyun Bae, Eugene Shin, Yong-ho Lee, Byung-Wan Lee, Eun Seok Kang, Bong-Soo Cha
    Diabetes & Metabolism Journal.2021; 45(6): 921.     CrossRef
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  • Ipragliflozin Additively Ameliorates Non-Alcoholic Fatty Liver Disease in Patients with Type 2 Diabetes Controlled with Metformin and Pioglitazone: A 24-Week Randomized Controlled Trial
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    Journal of Clinical Medicine.2020; 9(1): 259.     CrossRef
  • Stability Indicating, pH and pKa Dependent HPLC–DAD Method for the Simultaneous Determination of Weakly Ionizable Empagliflozin, Dapagliflozin and Canagliflozin in Pharmaceutical Formulations
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    Chromatographia.2020; 83(12): 1453.     CrossRef
  • Cardiorenal protection with SGLT2: Lessons from the cardiovascular outcome trials
    José Silva‐Cardoso, Omar Sheikh, Mouhamed Nashawi, Son Pham, Kelly M. Gallegos, Laith R. Dinkha, Robert J. Chilton
    Journal of Diabetes.2020; 12(4): 279.     CrossRef
  • Effect of the Sodium-Glucose Cotransporter 2 Inhibitor, Dapagliflozin, on Genitourinary Infection in an Animal Model of Type 2 Diabetes
    Jin Bong Choi, Je Mo Yoo, Ye-Jee Lee, Jae Woong Kim, Seung-Ju Lee, Hee Youn Kim, Dong Sup Lee, Seung-Hyun Ko, Hyun-Sop Choe
    International Neurourology Journal.2020; 24(1): 21.     CrossRef
  • Sodium‐glucose cotransporter 2 inhibitors regulate ketone body metabolism via inter‐organ crosstalk
    Jin Hee Kim, Minyoung Lee, Soo Hyun Kim, So Ra Kim, Byung‐Wan Lee, Eun Seok Kang, Bong‐Soo Cha, Jin Won Cho, Yong‐ho Lee
    Diabetes, Obesity and Metabolism.2019; 21(4): 801.     CrossRef
  • Effects of Sodium-Glucose Cotransporter 2 Inhibitors on Renal Outcomes in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
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  • SGLT2 inhibition with empagliflozin attenuates myocardial oxidative stress and fibrosis in diabetic mice heart
    Chenguang Li, Jie Zhang, Mei Xue, Xiaoyu Li, Fei Han, Xiangyang Liu, Linxin Xu, Yunhong Lu, Ying Cheng, Ting Li, Xiaochen Yu, Bei Sun, Liming Chen
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  • An update of SGLT1 and SGLT2 inhibitors in early phase diabetes-type 2 clinical trials
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  • A Lower Baseline Urinary Glucose Excretion Predicts a Better Response to the Sodium Glucose Cotransporter 2 Inhibitor
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  • Predictors of the Therapeutic Efficacy and Consideration of the Best Combination Therapy of Sodium-Glucose Co-transporter 2 Inhibitors
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  • Efficacy and tolerability of novel triple combination therapy in drug-naïve patients with type 2 diabetes from the TRIPLE-AXEL trial: protocol for an open-label randomised controlled trial
    Nam Hoon Kim, Soo Lim, Soo Heon Kwak, Min Kyong Moon, Jun Sung Moon, Yong-ho Lee, Ho Chan Cho, Juneyoung Lee, Sin Gon Kim
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  • Effect of Empagliflozin, a Selective Sodium-Glucose Cotransporter 2 Inhibitor, on Kidney and Peripheral Nerves in Streptozotocin-Induced Diabetic Rats
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  • The effect of Ramadan fasting and continuing sodium-glucose co-transporter-2 (SGLT2) inhibitor use on ketonemia, blood pressure and renal function in Muslim patients with type 2 diabetes
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  • Effect of Dapagliflozin on Alanine Aminotransferase Improvement in Type 2 Diabetes Mellitus with Non-alcoholic Fatty Liver Disease
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  • Comparison between sodium–glucose cotransporter 2 inhibitors and pioglitazone as additions to insulin therapy in type 2 diabetes patients: A systematic review with an indirect comparison meta‐analysis
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  • Characteristics of Dapagliflozin Responders: A Longitudinal, Prospective, Nationwide Dapagliflozin Surveillance Study in Korea
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  • Combining SGLT2 Inhibition With a Thiazolidinedione Additively Attenuate the Very Early Phase of Diabetic Nephropathy Progression in Type 2 Diabetes Mellitus
    Eugene Han, Eugene Shin, Gyuri Kim, Ji-Yeon Lee, Yong-ho Lee, Byung-Wan Lee, Eun Seok Kang, Bong-Soo Cha
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    European Journal of Pharmacology.2017; 812: 64.     CrossRef
  • Efficacy and safety of tofogliflozin in Japanese patients with type 2 diabetes mellitus with inadequate glycaemic control on insulin therapy (J‐STEP/INS): Results of a 16‐week randomized, double‐blind, placebo‐controlled multicentre trial
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  • A comparison of effects of DPP-4 inhibitor and SGLT2 inhibitor on lipid profile in patients with type 2 diabetes
    Seon-Ah Cha, Yong-Moon Park, Jae-Seung Yun, Tae-Seok Lim, Ki-Ho Song, Ki-Dong Yoo, Yu-Bae Ahn, Seung-Hyun Ko
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  • Morning Spot Urine Glucose-to-Creatinine Ratios Predict Overnight Urinary Glucose Excretion in Patients With Type 2 Diabetes
    So Ra Kim, Yong-ho Lee, Sang-Guk Lee, Sun Hee Lee, Eun Seok Kang, Bong-Soo Cha, Hyun Chul Lee, Jeong-Ho Kim, Byung-Wan Lee
    Annals of Laboratory Medicine.2017; 37(1): 9.     CrossRef
  • The Relationship between Increases in Morning Spot Urinary Glucose Excretion and Decreases in HbA1C in Patients with Type 2 Diabetes After Taking an SGLT2 Inhibitor: A Retrospective, Longitudinal Study
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  • Clinical and Genetic Features of Patients With Type 2 Diabetes and Renal Glycosuria
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    The Journal of Clinical Endocrinology & Metabolism.2017; 102(5): 1548.     CrossRef
  • Effect of Sodium-Glucose Co-Transporter 2 Inhibitor, Dapagliflozin, on Renal Renin-Angiotensin System in an Animal Model of Type 2 Diabetes
    Seok Joon Shin, Sungjin Chung, Soo Jung Kim, Eun-Mi Lee, Young-Hye Yoo, Ji-Won Kim, Yu-Bae Ahn, Eun-Sook Kim, Sung-Dae Moon, Myung-Jun Kim, Seung-Hyun Ko, Kwang-Hyun Baek
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  • Insulin resistance, role of metformin and other non-insulin therapies in pediatric type 1 diabetes
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    Pediatric Diabetes.2016; 17(8): 545.     CrossRef
  • Renal threshold for glucose reabsorption predicts diabetes improvement by sodium‐glucose cotransporter 2 inhibitor therapy
    Aya Osaki, Shuichi Okada, Tsugumichi Saito, Eijiro Yamada, Kumeo Ono, Yawara Niijima, Hiroto Hoshi, Masanobu Yamada
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  • A simple and sensitive high performance liquid chromatography assay with a fluorescence detector for determination of canagliflozin in human plasma
    Muzaffar Iqbal, Nasr Y. Khalil, Amer M. Alanazi, Khalid A. Al-Rashood
    Analytical Methods.2015; 7(7): 3028.     CrossRef
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