Diabetes & Metabolism Journal

Original Articles

Drug/Regimen
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, on Behalf of Investigators of ENVELOP Study; Received May 9, 2024 Accepted August 14, 2024 Published online January 6, 2025; DOI: https://doi.org/10.4093/dmj.2024.0238 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: 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.

Metabolic Risk/Epidemiology
Kidney Gastrin/CCKBR Attenuates Type 2 Diabetes Mellitus by Inhibiting SGLT2-Mediated Glucose Reabsorption through Erk/NF-κB Signaling Pathway: Xue Zhang, Yuhan Zhang, Yang Shi, Dou Shi, Min Niu, Xue Liu, Xing Liu, Zhiwei Yang, Xianxian Wu; Received November 6, 2023 Accepted September 7, 2024 Published online December 24, 2024; DOI: https://doi.org/10.4093/dmj.2023.0397 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
Both sodium-glucose cotransporters (SGLTs) and Na+/H+ exchangers (NHEs) rely on a favorable Na-electrochemical gradient. Gastrin, through the cholecystokinin B receptor (CCKBR), can induce natriuresis and diuresis by inhibiting renal NHEs activity. The present study aims to unveil the role of renal CCKBR in diabetes through SGLT2-mediated glucose reabsorption.
Methods
Renal tubule-specific Cckbr-knockout (Cckbr^CKO) mice and wild-type (WT) mice were utilized to investigate the effect of renal CCKBR on SGLT2 and systemic glucose homeostasis under normal diet, high-fat diet (HFD), and HFD with a subsequent injection of a low dose of streptozotocin. The regulation of SGLT2 expression by gastrin/CCKBR and the underlying mechanism was explored using human kidney (HK)-2 cells.
Results
CCKBR was downregulated in kidneys of diabetic mice. Compared with WT mice, Cckbr^CKO mice exhibited a greater susceptibility to obesity and diabetes when subjected to HFD. In vitro experiments using HK-2 cells revealed an upregulation of glucose transporters after incubation with high glucose, a response that was significantly attenuated following gastrin intervention. The glucose uptake from the culture medium of cells was altered accordingly. Moreover, gastrin administration effectively mitigated hyperglycemia in WT diabetic mice by inhibition of SGLT2 mediated glucose reabsorption, but this effect was compromised in the absence of CCKBR, as seen in Cckbr^CKO mice. Mechanistically, gastrin/CCKBR substantially reduced SGLT2 expression in HK-2 cells exposed to high glucose, via modulating Erk/nuclear factor-kappa B (NF-κB) pathway.
Conclusion
Our study underscores the crucial role of renal gastrin/CCKBR in SGLT2 regulation and glucose reabsorption, and renal gastrin/CCKBR can be a promising therapeutic target for diabetes.

Review

Drug/Regimen
Benefit and Safety of Sodium-Glucose Co-Transporter 2 Inhibitors in Older Patients with Type 2 Diabetes Mellitus: Ja Young Jeon, Dae Jung Kim; Diabetes Metab J. 2024;48(5):837-846. Published online September 1, 2024; DOI: https://doi.org/10.4093/dmj.2024.0317

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People with type 2 diabetes mellitus (T2DM) are at higher risk of developing cardiovascular disease, heart failure, chronic kidney disease, and premature death than people without diabetes. Therefore, treatment of diabetes aims to reduce these complications. Sodium-glucose co-transporter 2 (SGLT2) inhibitors have shown beneficial effects on cardiorenal and metabolic health beyond glucose control, making them a promising class of drugs for achieving the ultimate goals of diabetes treatment. However, despite their proven benefits, the use of SGLT2 inhibitors in eligible patients with T2DM remains suboptimal due to reports of adverse events. The use of SGLT2 inhibitors is particularly limited in older patients with T2DM because of the lack of treatment experience and insufficient long-term safety data. This article comprehensively reviews the risk-benefit profile of SGLT2 inhibitors in older patients with T2DM, drawing on data from prospective randomized controlled trials of cardiorenal outcomes, original studies, subgroup analyses across different age groups, and observational cohort studies.

Citations

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Trends in prescribing sodium‐glucose cotransporter 2 inhibitors for individuals with type 2 diabetes with and without cardiovascular‐renal disease in South Korea, 2015–2021
Kyoung Hwa Ha, Soyoung Shin, EunJi Na, Dae Jung Kim
Journal of Diabetes Investigation.2024;[Epub] CrossRef

Brief Report

Complications
Diabetic Ketoacidosis as an Effect of Sodium-Glucose Cotransporter 2 Inhibitor: Real World Insights: Han-Sang Baek, Chaiho Jeong, Yeoree Yang, Joonyub Lee, Jeongmin Lee, Seung-Hwan Lee, Jae Hyoung Cho, Tae-Seo Sohn, Hyun-Shik Son, Kun-Ho Yoon, Eun Young Lee; Diabetes Metab J. 2024;48(6):1169-1175. Published online June 10, 2024; DOI: https://doi.org/10.4093/dmj.2024.0036

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One of the notable adverse effects of sodium-glucose cotransporter 2 (SGLT2) inhibitor is diabetic ketoacidosis (DKA) often characterized by euglycemia. In this retrospective review of patients with DKA from 2015 to 2023, 21 cases of SGLT2 inhibitorassociated DKA were identified. Twelve (57.1%) exhibited euglycemic DKA (euDKA) while nine (42.9%) had hyperglycemic DKA (hyDKA). More than 90% of these cases were patients with type 2 diabetes mellitus. Despite similar age, sex, body mass index, and diabetes duration, individuals with hyDKA showed poorer glycemic control and lower C-peptide levels compared with euDKA. Renal impairment and acidosis were worse in the hyDKA group, requiring hemodialysis in two patients. Approximately one-half of hyDKA patients had concurrent hyperosmolar hyperglycemic state. Common symptoms included nausea, vomiting, general weakness, and dyspnea. Seizure was the initial manifestation of DKA in two cases. Infection and volume depletion were major contributors, while carbohydrate restriction and inadequate insulin treatment also contributed to SGLT2 inhibitor-associated DKA. Despite their beneficial effects, clinicians should be vigilant for SGLT2 inhibitor risk associated with DKA.

Citations

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Dapagliflozin/Empagliflozin/Ertugliflozin

Reactions Weekly.2025; 2042(1): 142. CrossRef
Diabetes mellitus im Alter
Andrej Zeyfang, Jürgen Wernecke, Anke Bahrmann
Diabetologie und Stoffwechsel.2024; 19(S 02): S226. CrossRef

Original Articles

Drug/Regimen
Pioglitazone as Add-on Therapy in Patients with Type 2 Diabetes Mellitus Inadequately Controlled with Dapagliflozin and Metformin: Double-Blind, Randomized, Placebo-Controlled Trial: Ji Hye Heo, Kyung Ah Han, Jun Hwa Hong, Hyun-Ae Seo, Eun-Gyoung Hong, Jae Myung Yu, Hye Seung Jung, Bong-Soo Cha; Diabetes Metab J. 2024;48(5):937-948. Published online February 2, 2024; DOI: https://doi.org/10.4093/dmj.2023.0314

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Background
This study assessed the efficacy and safety of triple therapy with pioglitazone 15 mg add-on versus placebo in patients with type 2 diabetes mellitus (T2DM) inadequately controlled with metformin and dapagliflozin.
Methods
In this multicenter, double-blind, randomized, phase 3 study, patients with T2DM with an inadequate response to treatment with metformin (≥1,000 mg/day) plus dapagliflozin (10 mg/day) were randomized to receive additional pioglitazone 15 mg/day (n=125) or placebo (n=125) for 24 weeks. The primary endpoint was the change in glycosylated hemoglobin (HbA1c) levels from baseline to week 24 (ClinicalTrials.gov identifier: NCT05101135).
Results
At week 24, the adjusted mean change from baseline in HbA1c level compared with placebo was significantly greater with pioglitazone treatment (–0.47%; 95% confidence interval, –0.61 to –0.33; P<0.0001). A greater proportion of patients achieved HbA1c <7% or <6.5% at week 24 with pioglitazone compared to placebo as add-on to 10 mg dapagliflozin and metformin (56.8% vs. 28% for HbA1c <7%, and 23.2% vs. 9.6% for HbA1c <6.5%; P<0.0001 for all). The addition of pioglitazone also significantly improved triglyceride, highdensity lipoprotein cholesterol levels, and homeostatic model assessment of insulin resistance levels, while placebo did not. The incidence of treatment-emergent adverse events was similar between the groups, and the incidence of fluid retention-related side effects by pioglitazone was low (1.5%).
Conclusion
Triple therapy with the addition of 15 mg/day of pioglitazone to dapagliflozin plus metformin was well tolerated and produced significant improvements in HbA1c in patients with T2DM inadequately controlled with dapagliflozin plus metformin.

Citations

Citations to this article as recorded by

Ideal Combination of Oral Hypoglycemic Agents for Patients with Type 2 Diabetes Mellitus
Hye Soon Kim
Diabetes & Metabolism Journal.2024; 48(5): 882. CrossRef

Drug/Regimen
Abrupt Decline in Estimated Glomerular Filtration Rate after Initiating Sodium-Glucose Cotransporter 2 Inhibitors Predicts Clinical Outcomes: A Systematic Review and Meta-Analysis: Min-Hsiang Chuang, Yu-Shuo Tang, Jui-Yi Chen, Heng-Chih Pan, Hung-Wei Liao, Wen-Kai Chu, Chung-Yi Cheng, Vin-Cent Wu, Michael Heung; Diabetes Metab J. 2024;48(2):242-252. Published online January 26, 2024; DOI: https://doi.org/10.4093/dmj.2023.0201

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Abstract PDF Supplementary Material PubReader ePub: Background
The initiation of sodium-glucose cotransporter-2 inhibitors (SGLT2i) typically leads to a reversible initial dip in estimated glomerular filtration rate (eGFR). The implications of this phenomenon on clinical outcomes are not well-defined.
Methods
We searched MEDLINE, Embase, and Cochrane Library from inception to March 23, 2023 to identify randomized controlled trials and cohort studies comparing kidney and cardiovascular outcomes in patients with and without initial eGFR dip after initiating SGLT2i. Pooled estimates were calculated using random-effect meta-analysis.
Results
We included seven studies in our analysis, which revealed that an initial eGFR dip following the initiation of SGLT2i was associated with less annual eGFR decline (mean difference, 0.64; 95% confidence interval [CI], 0.437 to 0.843) regardless of baseline eGFR. The risk of major adverse kidney events was similar between the non-dipping and dipping groups but reduced in patients with a ≤10% eGFR dip (hazard ratio [HR], 0.915; 95% CI, 0.865 to 0.967). No significant differences were observed in the composite of hospitalized heart failure and cardiovascular death (HR, 0.824; 95% CI, 0.633 to 1.074), hospitalized heart failure (HR, 1.059; 95% CI, 0.574 to 1.952), or all-cause mortality (HR, 0.83; 95% CI, 0.589 to 1.170). The risk of serious adverse events (AEs), discontinuation of SGLT2i due to AEs, kidney-related AEs, and volume depletion were similar between the two groups. Patients with >10% eGFR dip had increased risk of hyperkalemia compared to the non-dipping group.
Conclusion
Initial eGFR dip after initiating SGLT2i might be associated with less annual eGFR decline. There were no significant disparities in the risks of adverse cardiovascular outcomes between the dipping and non-dipping groups.

Drug/Regimen
Two-Year Therapeutic Efficacy and Safety of Initial Triple Combination of Metformin, Sitagliptin, and Empagliflozin in Drug-Naïve Type 2 Diabetes Mellitus Patients: Young-Hwan Park, Minji Sohn, So Yeon Lee, Soo Lim; Diabetes Metab J. 2024;48(2):253-264. Published online January 26, 2024; DOI: https://doi.org/10.4093/dmj.2023.0128

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Background
We investigated the long-term efficacy and safety of initial triple therapy using metformin, a dipeptidyl peptidase-4 inhibitor, and a sodium-glucose cotransporter-2 inhibitor, in patients with type 2 diabetes mellitus.
Methods
We enrolled 170 drug-naïve patients with glycosylated hemoglobin (HbA1c) level >7.5% who had started triple therapy (metformin, sitagliptin, and empagliflozin). Glycemic, metabolic, and urinary parameters were measured for 24 months.
Results
After 24 months, HbA1c level decreased significantly from 11.0%±1.8% to 7.0%±1.7%. At 12 and 24 months, the rates of achievement of the glycemic target goal (HbA1c <7.0%) were 72.5% and 61.7%, respectively, and homeostasis model assessment of β-cell function and insulin resistance indices improved. Whole-body fat percentage decreased by 1.08%, and whole-body muscle percentage increased by 0.97% after 24 months. Fatty liver indices and albuminuria improved significantly. The concentration of ketone bodies was elevated at the baseline but decreased after 24 months. There were no serious adverse events, including ketoacidosis.
Conclusion
Initial triple combination therapy with metformin, sitagliptin, and empagliflozin led to achievement of the glycemic target goal, which was maintained for 24 months without severe hypoglycemia but with improved metabolic function and albuminuria. This combination therapy may be a good strategy for drug-naïve patients with type 2 diabetes mellitus.

Citations

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Mechanistic insights and therapeutic potential of astilbin and apigenin in diabetic cardiomyopathy
Sachin Dhiman, Sanchit Dhankhar, Anjali Garg, Manni Rohilla, Monika Saini, Thakur Gurjeet Singh, Samrat Chauhan, Samy Selim, Soad K. Al Jaouni, Sabina Yasmin, Naseem Begum, Aziza Alshahrani, Mohammad Yousuf Ansari
Heliyon.2024; 10(21): e39996. CrossRef
Successful portosystemic shunt embolization resolves hepatic encephalopathy and enhances hepatic function and glycemic control in MASH-related cirrhosis: a case report
Yoshiaki Kobayashi, Takanobu Iwadare, Hiroyuki Kobayashi, Takefumi Kimura, Yoshiki Ozawa, Ryo Kodama, Masahiro Kurozumi, Yayoi Yamazaki, Yuki Yamashita, Takeji Umemura
Clinical Journal of Gastroenterology.2024;[Epub] CrossRef

Drug/Regimen
Risk of Diabetic Retinopathy between Sodium-Glucose Cotransporter-2 Inhibitors and Glucagon-Like Peptide-1 Receptor Agonists: Tzu-Yi Lin, Eugene Yu-Chuan Kang, Shih-Chieh Shao, Edward Chia-Cheng Lai, Sunir J. Garg, Kuan-Jen Chen, Je-Ho Kang, Wei-Chi Wu, Chi-Chun Lai, Yih-Shiou Hwang; Diabetes Metab J. 2023;47(3):394-404. Published online March 6, 2023; DOI: https://doi.org/10.4093/dmj.2022.0221

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Background
To compare risk of diabetic retinopathy (DR) between patients taking sodium-glucose cotransporter-2 inhibitors (SGLT2is) and those taking glucagon-like peptide-1 receptor agonists (GLP1-RAs) in routine care.
Methods
This retrospective cohort study emulating a target trial included patient data from the multi-institutional Chang Gung Research Database in Taiwan. Totally, 33,021 patients with type 2 diabetes mellitus using SGLT2is and GLP1-RAs between 2016 and 2019 were identified. 3,249 patients were excluded due to missing demographics, age <40 years, prior use of any study drug, a diagnosis of retinal disorders, a history of receiving vitreoretinal procedure, no baseline glycosylated hemoglobin, or no follow-up data. Baseline characteristics were balanced using inverse probability of treatment weighting with propensity scores. DR diagnoses and vitreoretinal interventions served as the primary outcomes. Occurrence of proliferative DR and DR receiving vitreoretinal interventions were regarded as vision-threatening DR.
Results
There were 21,491 SGLT2i and 1,887 GLP1-RA users included for the analysis. Patients receiving SGLT2is and GLP-1 RAs exhibited comparable rate of any DR (subdistribution hazard ratio [SHR], 0.90; 95% confidence interval [CI], 0.79 to 1.03), whereas the rate of proliferative DR (SHR, 0.53; 95% CI, 0.42 to 0.68) was significantly lower in the SGLT2i group. Also, SGLT2i users showed significantly reduced risk of composite surgical outcome (SHR, 0.58; 95% CI, 0.48 to 0.70).
Conclusion
Compared to those taking GLP1-RAs, patients receiving SGLT2is had a lower risk of proliferative DR and vitreoretinal interventions, although the rate of any DR was comparable between the SGLT2i and GLP1-RA groups. Thus, SGLT2is may be associated with a lower risk of vision-threatening DR but not DR development.

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Ehsan Rahimy, Euna B. Koo, Karen M. Wai, Cassie A. Ludwig, Andrea L. Kossler, Prithvi Mruthyunjaya
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Aikaterini Eleftheriadou, David Riley, Sizheng S. Zhao, Philip Austin, Gema Hernández, Gregory Y. H. Lip, Timothy L. Jackson, John P. H. Wilding, Uazman Alam
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American Journal of Ophthalmology.2024; 265: 39. CrossRef
Comparative Effectiveness of Glucagon-Like Peptide-1 Receptor Agonists, Sodium-Glucose Cotransporter 2 Inhibitors, Dipeptidyl Peptidase-4 Inhibitors, and Sulfonylureas for Sight-Threatening Diabetic Retinopathy
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Drug Regimen
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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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.

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Young Sang Lyu, Sangmo Hong, Si Eun Lee, Bo Young Cho, Cheol-Young Park
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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
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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

Review

Pathophysiology
Renoprotective Mechanism of Sodium-Glucose Cotransporter 2 Inhibitors: Focusing on Renal Hemodynamics: Nam Hoon Kim, Nan Hee Kim; Diabetes Metab J. 2022;46(4):543-551. Published online July 27, 2022; DOI: https://doi.org/10.4093/dmj.2022.0209

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Diabetic kidney disease (DKD) is a prevalent renal complication of diabetes mellitus that ultimately develops into end-stage kidney disease (ESKD) when not managed appropriately. Substantial risk of ESKD remains even with intensive management of hyperglycemia and risk factors of DKD and timely use of renin-angiotensin-aldosterone inhibitors. Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce hyperglycemia primarily by inhibiting glucose and sodium reabsorption in the renal proximal tubule. Currently, their effects expand to prevent or delay cardiovascular and renal adverse events, even in those without diabetes. In dedicated renal outcome trials, SGLT2 inhibitors significantly reduced the risk of composite renal adverse events, including the development of ESKD or renal replacement therapy, which led to the positioning of SGLT2 inhibitors as the mainstay of chronic kidney disease management. Multiple mechanisms of action of SGLT2 inhibitors, including hemodynamic, metabolic, and anti-inflammatory effects, have been proposed. Restoration of tubuloglomerular feedback is a plausible explanation for the alteration in renal hemodynamics induced by SGLT2 inhibition and for the associated renal benefit. This review discusses the clinical rationale and mechanism related to the protection SGLT2 inhibitors exert on the kidney, focusing on renal hemodynamic effects.

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Original Articles

Drug/Regimen
Safety and Effectiveness of Empagliflozin in Korean Patients with Type 2 Diabetes Mellitus: Results from a Nationwide Post-Marketing Surveillance: Jun Sung Moon, Nam Hoon Kim, Jin Oh Na, Jae Hyoung Cho, In-Kyung Jeong, Soon Hee Lee, Ji-Oh Mok, Nan Hee Kim, Dong Jin Chung, Jinhong Cho, Dong Woo Lee, Sun Woo Lee, Kyu Chang Won; Diabetes Metab J. 2023;47(1):82-91. Published online June 20, 2022; DOI: https://doi.org/10.4093/dmj.2021.0356

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Background
To evaluate the safety and effectiveness of empagliflozin in routine clinical settings, we collected and assessed the clinical profiles of Korean patients with type 2 diabetes mellitus.
Methods
This was a post-marketing surveillance study of empagliflozin 10 and 25 mg. Information on adverse events and adverse drug reactions (ADRs) was collected as safety data sets. Available effectiveness outcomes, including glycosylated hemoglobin (HbA1c) level, fasting plasma glucose, body weight, and blood pressure, were assessed.
Results
The incidence rate of ADRs was 5.14% in the safety dataset (n=3,231). Pollakiuria, pruritis genital, and weight loss were the most common ADRs. ADRs of special interest accounted for only 1.18%, and there were no serious events that led to mortality or hospitalization. In the effectiveness data set (n=2,567), empagliflozin significantly reduced the mean HbA1c level and body weight during the study period by –0.68%±1.39% and –1.91±3.37 kg (both P<0.0001), respectively. In addition, shorter disease duration, absence of dyslipidemia, and higher baseline HbA1c levels were identified as the clinical features characteristic of a “responder” to empagliflozin therapy.
Conclusion
Empagliflozin is a safe and potent glucose-lowering drug in routine use among Korean patients with type 2 diabetes mellitus. It is expected to have better glycemic efficacy in Korean patients with poorly controlled type 2 diabetes mellitus.

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Evaluation of Efficacy and Safety of Empagliflozin in Bangladeshi Patients with Type 2 Diabetes Mellitus (EFFISAEM Study)
Mohammad Saifuddin, Ajit K. Paul, Sultana M. Shefin, Md. Jahangir Alam, Shahjada Selim, Sunjida Islam, Tanjina Hossain, Sadiqa Tuqan, Nusrat Sultana, Marufa Mustari, Ramen C. Basak, Kazi A. Aftab, Indrajit Prasad, Mohammad R. Uddin, Shoma Sharker, Md. Abu
Indian Journal of Endocrinology and Metabolism.2024; 28(5): 500. CrossRef
Blood pressure reduction with empagliflozin in Japanese patients with type 2 diabetes and cardiovascular diseases: a post-hoc sub-analysis of the placebo-controlled randomized EMBLEM trial
Atsushi Tanaka, Michio Shimabukuro, Hiroki Teragawa, Hisako Yoshida, Yosuke Okada, Toshinari Takamura, Isao Taguchi, Shigeru Toyoda, Hirofumi Tomiyama, Shinichiro Ueda, Yukihito Higashi, Koichi Node, Junya Ako, Hirohisa Amano, Itaru Hisauchi, Yumi Ikehara
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Comparison of the Pharmacokinetics, Safety, and Tolerability of Two Empagliflozin Formulations in Healthy Korean Subjects
Xu Jiang, Sungyeun Bae, Deok Yong Yoon, Shin Jung Park, Jaeseong Oh, Joo-Youn Cho, Kyung-Sang Yu
Drug Design, Development and Therapy.2023; Volume 17: 2137. CrossRef
Comparative safety of different sodium-glucose transporter 2 inhibitors in patients with type 2 diabetes: a systematic review and network meta-analysis of randomized controlled trials
Chun Xing Li, Li Yan Liu, Chen Xiao Zhang, Xu Hua Geng, Si Meng Gu, Yu Qiao Wang, Hua Liu, Qing Xie, Shuo Liang
Frontiers in Endocrinology.2023;[Epub] CrossRef

Drug/Regimen
Real-World Prescription Patterns and Barriers Related to the Use of Sodium-Glucose Cotransporter 2 Inhibitors among Korean Patients with Type 2 Diabetes Mellitus and Cardiovascular Disease: Jong Ha Baek, Ye Seul Yang, Seung-Hyun Ko, Kyung Do Han, Jae Hyeon Kim, Min Kyong Moon, Jong Suk Park, Byung-Wan Lee, Tae Jung Oh, Suk Chon, Jong Han Choi, Kyu Yeon Hur, Committee of Clinical Practice Guidelines, Korean Diabetes Association; Diabetes Metab J. 2022;46(5):701-712. Published online June 3, 2022; DOI: https://doi.org/10.4093/dmj.2022.0002

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Background
To evaluate prescription trends and clinical factors of the sodium-glucose cotransporter 2 inhibitors (SGLT2i) use according to the presence of atherosclerotic cardiovascular disease (ASCVD) or heart failure (HF) in Korean patients with type 2 diabetes mellitus (T2DM).
Methods
Prescription patterns of SGLT2i use between 2015 and 2019 were determined using the Korean National Health Insurance Service database of claims.
Results
Of all patients with T2DM (n=4,736,493), the annual prescription rate of SGLT2i increased every year in patients with ASCVD (from 2.2% to 10.7%) or HF (from 2.0% to 11.1%). After the first hospitalization for ASCVD (n=518,572), 13.7% (n=71,259) of patients initiated SGLT2i with a median of 10.6 months. After hospitalization for HF (n=372,853), 11.2% (n=41,717) of patients initiated SGLT2i after a median of 8.8 months. In multivariate regression for hospitalization, older age (per 10 years, odds ratio [OR], 0.57; 95% confidence interval [CI], 0.56 to 0.57), lower household income (OR, 0.93; 95% CI, 0.92 to 0.95), rural residents (OR, 0.95; 95% CI, 0.93 to 0.97), and dipeptidyl peptidase-4 inhibitor (DPP-4i) users (OR, 0.82; 95% CI, 0.81 to 0.84) were associated with lesser initiation of SGLT2i in ASCVD. Additionally, female gender (OR, 0.97; 95% CI, 0.95 to 0.99) was associated with lesser initiation of SGLT2i in HF.
Conclusion
The prescription rate of SGLT2i increased gradually up to 2019 but was suboptimal in patients with ASCVD or HF. After the first hospitalization for ASCVD or HF, older age, female gender, low household income, rural residents, and DPP-4i users were less likely to initiate SGLT2i.

Citations

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Effectiveness and safety of sodium–glucose cotransporter 2 inhibitors in Asian populations
Kyoung Hwa Ha, Dae Jung Kim
Journal of Diabetes Investigation.2024; 15(3): 285. CrossRef
Real-World Treatment Patterns according to Clinical Practice Guidelines in Patients with Type 2 Diabetes Mellitus and Established Cardiovascular Disease in Korea: Multicenter, Retrospective, Observational Study
Ye Seul Yang, Nam Hoon Kim, Jong Ha Baek, Seung-Hyun Ko, Jang Won Son, Seung-Hwan Lee, Sang Youl Rhee, Soo-Kyung Kim, Tae Seo Sohn, Ji Eun Jun, In-Kyung Jeong, Chong Hwa Kim, Keeho Song, Eun-Jung Rhee, Junghyun Noh, Kyu Yeon Hur
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Hospital Readmissions for Fluid Overload among Individuals with Diabetes and Diabetic Kidney Disease: Risk Factors and Multivariable Prediction Models
Jiashen Cai, Dorothy Huang, Hanis Binte Abdul Kadir, Zhihua Huang, Li Choo Ng, Andrew Ang, Ngiap Chuan Tan, Yong Mong Bee, Wei Yi Tay, Chieh Suai Tan, Cynthia C. Lim
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Kidney outcomes with SGLT2 inhibitor versus DPP4 inhibitor use in older adults with diabetes
Yuta Suzuki, Hidehiro Kaneko, Akira Okada, Jin Komuro, Toshiyuki Ko, Katsuhito Fujiu, Norifumi Takeda, Hiroyuki Morita, Akira Nishiyama, Masaki Ieda, Koichi Node, Hideo Yasunaga, Masaomi Nangaku, Issei Komuro
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Benefit and Safety of Sodium-Glucose Co-Transporter 2 Inhibitors in Older Patients with Type 2 Diabetes Mellitus
Ja Young Jeon, Dae Jung Kim
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Impact of Chronic Kidney Disease and Gout on End-Stage Renal Disease in Type 2 Diabetes: Population-Based Cohort Study
Inha Jung, Da Young Lee, Seung Min Chung, So Young Park, Ji Hee Yu, Jun Sung Moon, Ji A Seo, Kyungdo Han, Nan Hee Kim
Endocrinology and Metabolism.2024; 39(5): 748. CrossRef
Income-Related Disparities in Mortality Among Young Adults With Type 2 Diabetes
Ji Yoon Kim, Sojeong Park, Minae Park, Nam Hoon Kim, Sin Gon Kim
JAMA Network Open.2024; 7(11): e2443918. CrossRef
Association of Succinate and Adenosine Nucleotide Metabolic Pathways with Diabetic Kidney Disease in Patients with Type 2 Diabetes Mellitus
Inha Jung, Seungyoon Nam, Da Young Lee, So Young Park, Ji Hee Yu, Ji A Seo, Dae Ho Lee, Nan Hee Kim
Diabetes & Metabolism Journal.2024; 48(6): 1126. CrossRef
Evaluating the appropriateness and the factors associated with sodium-glucose co-transporter 2 inhibitors prescribing in a Middle Eastern country: a cross-sectional study
Nancy Zaghloul, Ahmed Awaisu, Ahmed Mahfouz, Zainab Ali, Sumaya Alyafei, Hazem Elewa
International Journal of Clinical Pharmacy.2024;[Epub] CrossRef
Trends in prescribing sodium‐glucose cotransporter 2 inhibitors for individuals with type 2 diabetes with and without cardiovascular‐renal disease in South Korea, 2015–2021
Kyoung Hwa Ha, Soyoung Shin, EunJi Na, Dae Jung Kim
Journal of Diabetes Investigation.2024;[Epub] CrossRef
Prescribing patterns of SGLT-2 inhibitors for patients with heart failure: A two-center analysis
Teja Chakrala, Roshni O. Prakash, Justin Kim, Hanzhi Gao, Umar Ghaffar, Jaymin Patel, Alex Parker, Bhagwan Dass
American Heart Journal Plus: Cardiology Research and Practice.2023; 28: 100286. CrossRef
Risk of developing chronic kidney disease in young-onset Type 2 diabetes in Korea
Joonyub Lee, Seung-Hwan Lee, Kun-Ho Yoon, Jae Hyoung Cho, Kyungdo Han, Yeoree Yang
Scientific Reports.2023;[Epub] CrossRef
Comparison of SGLT2 inhibitors with DPP-4 inhibitors combined with metformin in patients with acute myocardial infarction and diabetes mellitus
Young Sang Lyu, Seok Oh, Jin Hwa Kim, Sang Yong Kim, Myung Ho Jeong
Cardiovascular Diabetology.2023;[Epub] CrossRef
Severe hypoglycemia as a risk factor for cardiovascular outcomes in patients with type 2 diabetes: is it preventable?
Seung-Hyun Ko
Cardiovascular Prevention and Pharmacotherapy.2022; 4(3): 106. CrossRef
Association between the Diabetes Drug Cost and Cardiovascular Events and Death in Korea: A National Health Insurance Service Database Analysis
Seung Min Chung, Ji-In Lee, Eugene Han, Hyun-Ae Seo, Eonju Jeon, Hye Soon Kim, Ji Sung Yoon
Endocrinology and Metabolism.2022; 37(5): 759. CrossRef

Cardiovascular Risk/Epidemiology
Comparative Effects of Sodium-Glucose Cotransporter 2 Inhibitor and Thiazolidinedione Treatment on Risk of Stroke among Patients with Type 2 Diabetes Mellitus: Seung Eun Lee, Hyewon Nam, Han Seok Choi, Hoseob Kim, Dae-Sung Kyoung, Kyoung-Ah Kim; Diabetes Metab J. 2022;46(4):567-577. Published online February 8, 2022; DOI: https://doi.org/10.4093/dmj.2021.0160

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Background
Although cardiovascular outcome trials using sodium-glucose cotransporter-2 inhibitors (SGLT-2i) showed a reduction in risk of 3-point major adverse cardiovascular events (MACE), they did not demonstrate beneficial effects on stroke risk. Additionally, meta-analysis showed SGLT-2i potentially had an adverse effect on stroke risk. Contrarily, pioglitazone, a type of thiazolidinedione (TZD), has been shown to reduce recurrent stroke risk. Thus, we aimed to compare the effect of SGLT-2i and TZD on the risk of stroke in type 2 diabetes mellitus (T2DM) patients.
Methods
Using the Korean National Health Insurance Service data, we compared a 1:1 propensity score-matched cohort of patients who used SGLT-2i or TZD from January 2014 to December 2018. The primary outcome was stroke. The secondary outcomes were myocardial infarction (MI), cardiovascular death, 3-point MACE, and heart failure (HF).
Results
After propensity-matching, each group included 56,794 patients. Baseline characteristics were well balanced. During the follow-up, 862 patients were newly hospitalized for stroke. The incidence rate of stroke was 4.11 and 4.22 per 1,000 person-years for the TZD and SGLT-2i groups respectively. The hazard ratio (HR) of stroke was 1.054 (95% confidence interval [CI], 0.904 to 1.229) in the SGLT-2i group compared to the TZD group. There was no difference in the risk of MI, cardiovascular death, 3-point MACE between groups. Hospitalization for HF was significantly decreased in SGLT-2i-treated patients (HR, 0.645; 95% CI, 0.466 to 0.893). Results were consistent regardless of prior cardiovascular disease.
Conclusion
In this real-world data, the risk of stroke was comparable in T2DM patients treated with SGLT-2i or TZD.

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Similar incidence of stroke with SGLT2 inhibitors and GLP-1 receptor agonists in real-world cohort studies among patients with type 2 diabetes
André J. Scheen
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Inês Henriques Vieira, Tânia Santos Carvalho, Joana Saraiva, Leonor Gomes, Isabel Paiva
Biomedicines.2024; 12(5): 1102. CrossRef
Key results from observational studies and real‐world evidence of sodium‐glucose cotransporter‐2 inhibitor effectiveness and safety in reducing cardio‐renal risk
Thomas Nyström
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A Green Approach: Optimization of the UPLC Method Using DoE Software for Concurrent Quantification of Pioglitazone and Dapagliflozin in a SNEDDS Formulation for the Treatment of Diabetes
Ehab M. Elzayat, Abdelrahman Y. Sherif, Mohamed W. Attwa, Mohammad A. Altamimi
ACS Omega.2024; 9(45): 45011. CrossRef
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Lobeglitazone, a novel thiazolidinedione, for secondary prevention in patients with ischemic stroke: a nationwide nested case-control study
Joonsang Yoo, Jimin Jeon, Minyoul Baik, Jinkwon Kim
Cardiovascular Diabetology.2023;[Epub] CrossRef
Do SGLT2 inhibitors and GLP-1 receptor agonists modulate differently the risk of stroke ? Discordance between randomised controlled trials and observational studies
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Diabetes & Metabolism.2023; 49(5): 101474. CrossRef

Short Communication

Drug/Regimen
Clinical Efficacy of Sodium-Glucose Cotransporter 2 Inhibitor and Glucagon-Like Peptide-1 Receptor Agonist Combination Therapy in Type 2 Diabetes Mellitus: Real-World Study: Hwi Seung Kim, Taekwan Yoon, Chang Hee Jung, Joong-Yeol Park, Woo Je Lee; Diabetes Metab J. 2022;46(4):658-662. Published online November 8, 2021; DOI: https://doi.org/10.4093/dmj.2021.0232

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Sodium-glucose cotransporter 2 inhibitor (SGLT2i) and glucagon-like peptide-1 receptor agonist (GLP-1RA) are novel anti-diabetic drugs whose glucose-lowering effect and cardiovascular and renal benefits were evidenced in clinical trials. We investigated the real-world efficacy and safety of the combination of SGLT2i and GLP-1RA in patients with type 2 diabetes mellitus in Korea. The medical records of 104 patients who maintained the combination for at least 1 year were retrospectively reviewed. The change in glycosylated hemoglobin (HbA1c) after 6 months and 1 year of treatment was evaluated. The mean age was 51 years, and 41% were female. The mean baseline HbA1c, body mass index, and duration of diabetes were 9.0%, 28.8 kg/m², and 11.7 years, respectively. Compared with baseline, the HbA1c decreased by 1.5% (95% confidence interval [CI], 1.27 to 1.74; P<0.001) after 6 months and by 1.4% (95% CI, 1.19 to 1.70; P<0.001) after 1 year. Over 1 year, the bodyweight change was −2.8 kg (95% CI, −4.21 to −1.47; P<0.001). The combination of SGLT2i and GLP-1RA is effective and tolerable in type 2 diabetes mellitus patients in real-world practice.

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Effectiveness and safety of the combination of sodium–glucose transport protein 2 inhibitors and glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes mellitus: a systematic review and meta-analysis of observational studies
Aftab Ahmad, Hani Sabbour
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Sodium–Glucose Cotransporter Inhibitors: Cellular Mechanisms Involved in the Lipid Metabolism and the Treatment of Chronic Kidney Disease Associated with Metabolic Syndrome
Fernando Cortés-Camacho, Oscar René Zambrano-Vásquez, Elena Aréchaga-Ocampo, Jorge Ismael Castañeda-Sánchez, José Guillermo Gonzaga-Sánchez, José Luis Sánchez-Gloria, Laura Gabriela Sánchez-Lozada, Horacio Osorio-Alonso
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António Cabral Lopes, Olga Lourenço, Manuel Morgado
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Hormonal Gut–Brain Signaling for the Treatment of Obesity
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All‐cause mortality and cardiovascular outcomes with sodium‐glucose Co‐transporter 2 inhibitors, glucagon‐like peptide‐1 receptor agonists and with combination therapy in people with type 2 diabetes
David R. Riley, Hani Essa, Philip Austin, Frank Preston, Isatu Kargbo, Gema Hernández Ibarburu, Ramandeep Ghuman, Daniel J. Cuthbertson, Gregory Y. H. Lip, Uazman Alam
Diabetes, Obesity and Metabolism.2023; 25(10): 2897. CrossRef
The Efficacy and Safety of the Combination Therapy With GLP-1 Receptor Agonists and SGLT-2 Inhibitors in Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis
Chen Li, Jie Luo, Mingyan Jiang, Keke Wang
Frontiers in Pharmacology.2022;[Epub] CrossRef
Clinical Efficacy of Sodium-Glucose Cotransporter 2 Inhibitor and Glucagon-Like Peptide-1 Receptor Agonist Combination Therapy in Type 2 Diabetes Mellitus: Real-World Study (Diabetes Metab J 2022;46: 658-62)
Hwi Seung Kim, Woo Je Lee
Diabetes & Metabolism Journal.2022; 46(4): 665. CrossRef
Clinical Efficacy of Sodium-Glucose Cotransporter 2 Inhibitor and Glucagon-Like Peptide-1 Receptor Agonist Combination Therapy in Type 2 Diabetes Mellitus: Real-World Study (Diabetes Metab J 2022;46: 658-62)
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Original Article

Basic Research
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 Metab J. 2021;45(6):921-932. Published online February 22, 2021; DOI: https://doi.org/10.4093/dmj.2020.0187

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Background
Sodium-glucose co-transporter 2 (SGLT2) inhibitors are a new class of antidiabetic drugs that exhibit multiple extraglycemic effects. However, there are conflicting results regarding the effects of SGLT2 inhibition on energy expenditure and thermogenesis. Therefore, we investigated the effect of ipragliflozin (a selective SGLT2 inhibitor) on energy metabolism.
Methods
Six-week-old male 129S6/Sv mice with a high propensity for adipose tissue browning were randomly assigned to three groups: normal chow control, 60% high-fat diet (HFD)-fed control, and 60% HFD-fed ipragliflozin-treated groups. The administration of diet and medication was continued for 16 weeks.
Results
The HFD-fed mice became obese and developed hepatic steatosis and adipose tissue hypertrophy, but their random glucose levels were within the normal ranges; these features are similar to the metabolic features of a prediabetic condition. Ipragliflozin treatment markedly attenuated HFD-induced hepatic steatosis and reduced the size of hypertrophied adipocytes to that of smaller adipocytes. In the ipragliflozin treatment group, uncoupling protein 1 (Ucp1) and other thermogenesis-related genes were significantly upregulated in the visceral and subcutaneous adipose tissue, and fatty acid oxidation was increased in the brown adipose tissue. These effects were associated with a significant reduction in the insulin-to-glucagon ratio and the activation of the AMP-activated protein kinase (AMPK)/sirtuin 1 (SIRT1) pathway in the liver and adipose tissue.
Conclusion
SGLT2 inhibition by ipragliflozin showed beneficial metabolic effects in 129S6/Sv mice with HFD-induced obesity that mimics prediabetic conditions. Our data suggest that SGLT2 inhibitors, through their upregulation of energy expenditure, may have therapeutic potential in prediabetic obesity.

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International Journal of Molecular Sciences.2022; 23(10): 5634. CrossRef
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