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      • KCI등재

        Sodium/glucose Co-Transporter 2 Inhibitor, Empagliflozin, Alleviated Transient Expression of SGLT2 after Myocardial Infarction

        이수용,이태욱,Gyu Tae Park,Jae Ho Kim,이현채,Jung-Hwa Han,Aeseon Yoon,Dahye Yoon,Shukmann Kim,Soon Myung Jung,Jin Hee Choi,Min Ku Chon,Sang Hyun Lee,Ki Won Hwang,Jeongsu Kim,Yong Hyun Park,June Hong Kim,Kook J 대한심장학회 2021 Korean Circulation Journal Vol.51 No.3

        Background and Objectives: Large clinical studies of sodium/glucose cotransporter 2 (SGLT2) inhibitors have shown a significant beneficial effect on heart failure-associated hospitalization and cardiovascular events. As SGLT2 is known to be absent in heart cells, improved cardiovascular outcomes are thought to be accounted for by the indirect effects of the drug. We sought to confirm whether such benefits were mediated through SGLT2 expressed in the heart using myocardial infarction (MI) model. Methods: Mice pre-treated with empagliflozin (EMPA), an SGLT2 inhibitor, showed a significantly reduced infarct size compared with the vehicle group three days post-MI. Interestingly, we confirmed SGLT2 localized in the infarct zone. The sequential changes of SGLT2 expression after MI were also evaluated. Results: One day after MI, SGLT2 transiently appeared in the ischemic areas in the vehicle group and increased until 72 hours. The appearance of SGLT2 was delayed and less in amount compared with the vehicle group. Additionally, there was a significant difference in metabolites, including glucose and amino acids in the 1H nuclear magnetic resonance analysis between groups. Conclusions: Our work demonstrates that SGLT2 is transiently expressed in heart tissue early after MI and EMPA may directly operate on SGLT2 to facilitate metabolic substrates shifts.

      • KCI등재

        Anti-Inflammatory Effect for Atherosclerosis Progression by Sodium-Glucose Cotransporter 2 (SGLT-2) Inhibitor in a Normoglycemic Rabbit Model

        이슬기,Seung-Jun Lee,Jung-Jae Lee,Jung-SunKim,Oh-Hyun Lee,김충기,Darae Kim,Yong-Ho Lee,JaeWonOh,Se Il Park,전옥희,Sung-Jin Hong,Chul-Min Ahn,Byeong-Keuk Kim,Young-Guk Ko,Donghoon Choi,Myeong-Ki Hong,Yangsoo Ja 대한심장학회 2020 Korean Circulation Journal Vol.50 No.5

        Background and Objectives: We sought to investigate an anti-atherosclerotic and anti-inflammatory effect of sodium-glucose cotransporter-2 (SGLT-2) inhibitors in normoglycemic atherosclerotic rabbit model. Methods: Male New Zealand white rabbits (n=26) were fed with a 1% high-cholesterol diet for 7 weeks followed by normal diet for 2 weeks. After balloon catheter injury, the rabbits were administered with the Dapagliflozin (1mg/kg/day) or control-medium for 8 weeks (n=13 for each group). All lesions were assessed with angiography, optical coherence tomography (OCT), and histological assessment. Results: Atheroma burden (38.51±3.16% vs. 21.91±1.22%, p<0.01) and lipid accumulation (18.90±3.63% vs. 10.20±2.03%, p=0.047) was significantly decreased by SGLT-2 inhibitor treatment. The SGLT-2 inhibitor group showed lower macrophage infiltration (20.23±1.89% vs. 12.72±1.95%, p=0.01) as well as tumor necrosis factor (TNF)-α expression (31.17±4.40% vs. 19.47±2.10%, p=0.025). Relative area of inducible nitric oxide synthase+ macrophages was tended to be lower in the SGLT-2 inhibitor-treated group (1.00±0.16% vs. 0.71±0.10%, p=0.13), while relative proportion of Arg1+ macrophage was markedly increased (1.00±0.27% vs. 2.43±0.64%, p=0.04). As a result, progression of atherosclerosis was markedly attenuated in SGLT-2 inhibitor treated group (OCT area stenosis, 32.13±1.20% vs. 22.77±0.88%, p<0.01). Mechanistically, SGLT-2 treatment mitigated the inflammatory responses in macrophage. Especially, Toll-like receptor 4/nuclear factor-kappa B signaling pathway, and their downstream effectors such as interleukin-6 and TNF-α were markedly suppressed by SGLT-2 inhibitor treatment. Conclusions: These results together suggest that SGLT-2 inhibitor exerts an anti-atherosclerotic effect through favorable modulation of inflammatory response as well as macrophage characteristics in non-diabetic situation.

      • KCI등재

        Predictors of the Therapeutic Efficacy and Consideration of the Best Combination Therapy of Sodium-Glucose Co-transporter 2 Inhibitors

        이지연,조용인,이민영,김유진,이용호,이병완,차봉수,강은석 대한당뇨병학회 2019 Diabetes and Metabolism Journal Vol.43 No.2

        Background: We investigated the predictive markers for the therapeutic efficacy and the best combination of sodium-glucose cotransporter 2 (SGLT2) inhibitors (empagliflozin, dapagliflozin, and ipragliflozin) therapy in patients with type 2 diabetes mellitus (T2DM). Methods: A total of 804 patients with T2DM who had taken SGLT2 inhibitor as monotherapy or an add-on therapy were analyzed. Multivariate regression analyses were performed to identify the predictors of SGLT2 inhibitor response including the classes of baseline anti-diabetic medications. Results: After adjusting for age, sex, baseline body mass index (BMI), diabetes duration, duration of SGLT2 inhibitor use, initial glycosylated hemoglobin (HbA1c) level, estimated glomerular filtration rate (eGFR), and other anti-diabetic agent usage, multivariate analysis revealed that shorter diabetes duration, higher initial HbA1c and eGFR were associated with better glycemic response. However, baseline BMI was inversely correlated with glycemic status; lean subjects with well-controlled diabetes and obese subjects with inadequately controlled diabetes received more benefit from SGLT2 inhibitor treatment. In addition, dipeptidyl peptidase 4 (DPP4) inhibitor use was related to a greater reduction in HbA1c in patients with higher baseline HbA1c ≥7%. Sulfonylurea users experienced a larger change from baseline HbA1c but the significance was lost after adjustment for covariates and metformin and thiazolidinedione use did not affect the glycemic outcome. Conclusion: A better response to SGLT2 inhibitors is expected in Korean T2DM patients who have higher baseline HbA1c and eGFR with a shorter diabetes duration. Moreover, the add-on of an SGLT2 inhibitor to a DPP4 inhibitor is likely to show the greatest glycemic response.

      • KCI등재

        Cardiovascular Safety of Sodium Glucose Cotransporter 2 Inhibitors as Add-on to Metformin Monotherapy in Patients with Type 2 Diabetes Mellitus

        전자영,하경화,김대중 대한당뇨병학회 2021 Diabetes and Metabolism Journal Vol.45 No.4

        Background Using real-world data, cardiovascular safety was investigated in metformin users newly starting sodium glucose cotransporter 2 (SGLT2) inhibitors compared with other glucose-lowering drugs in Korea. Methods This was a retrospective observational study using the National Health Insurance Service claims database in Korea. The study period was from September 2014 to December 2016. The study included subjects who were newly prescribed SGLT2 inhibitors or other glucose-lowering drugs while on metformin monotherapy; cohort 1 was composed of new users of SGLT2 inhibitors versus dipeptidyl peptidase-4 (DPP-4) inhibitors and cohort 2 included new users of SGLT2 inhibitors versus sulfonylureas. To balance the patient characteristics, propensity score matching was performed at a 1:1 ratio. Cardiovascular outcomes included hospitalization for heart failure (HHF), all-cause mortality, HHF plus all-cause mortality, myocardial infarction (MI), stroke, and modified major adverse cardiovascular events (MACEs). Results After propensity score matching, each cohort group was well balanced at baseline (21,688 pairs in cohort 1 and 20,120 pairs in cohort 2). As the second-line treatment, use of SGLT2 inhibitors was associated with a lower risk of HHF and HHF plus all-cause mortality compared with DPP-4 inhibitors. In addition, use of SGLT2 inhibitors versus sulfonylurea as add-on therapy to metformin was associated with decreased risks of HHF, all-cause mortality, HHF plus all-cause mortality, MI, stroke, and modified MACEs. Conclusion SGLT2 inhibitors can be a good second-line drug to reduce the incidence of cardiovascular diseases compared with DPP-4 inhibitors or sulfonylureas in people with type 2 diabetes mellitus.

      • KCI등재

        Sodium-glucose cotransporter-2 inhibitor for renal function preservation in patients with type 2 diabetes mellitus: a Korean Diabetes Association and Korean Society of Nephrology consensus statement

        오태정,문주영,Kyu Yeon Hur,Seung Hyun Ko,Hyun Jung Kim,Taehee Kim,Dong Won Lee,Min Kyong Moon,The Committee of Clinical Practice Guideline,Korean Diabetes Association and Committee of the Cooperative Studie 대한신장학회 2020 Kidney Research and Clinical Practice Vol.39 No.3

        Diabetes is a leading cause of end-stage renal disease. Therefore, prevention of renal dysfunction is an important treatment goal in the management of diabetes. The data of landmark cardiovascular outcome trials of sodiumglucose cotransporter-2 (SGLT2) inhibitors showed profound reno-protective effects. The Korean Diabetes Association and the Korean Society of Nephrology reviewed clinical trials and performed a meta-analysis to assess the effects of SGLT2 inhibitors on the preservation of estimated glomerular filtration rate (eGFR). We limited the data of SGLT2 inhibitors which can be prescribed in Korea. Both eGFR value and its change from the baseline were significantly more preserved in the SGLT2-inhibitor treatment group compared to the control group after 156 weeks. However, some known adverse events were increased in SGLT2 inhibitor treatment, such as genital infection, diabetic ketoacidosis, and volume depletion. We recommend long-term use of SGLT2 inhibitors in patients with type 2 diabetes mellitus (T2DM) for attenuation of renal function decline. However, we cannot generalize our recommendations due to the lack of long-term clinical trials testing the reno-protective effects of every SGLT2 inhibitor in a broad range of patients with T2DM. This recommendation can be revised and updated after the publication of several large-scale renal outcome trials.

      • KCI등재

        Clinical implication of SGLT2 inhibitors in type 2 diabetes

        김고운,정성훈 대한약학회 2014 Archives of Pharmacal Research Vol.37 No.8

        Treatment of type 2 diabetes mellitus (T2DM)continues to present challenges, with many patients failingto achieve glycemic targets. Despite the availability ofmany oral and injectable anti-diabetic agents, therapeuticefficacy is often offset by undesirable side effects such ashypoglycemia, weight gain and cardiovascular complications. Therefore, the search for new therapeutic agents withan improved benefit–risk profile continues. Recent researchhas focused on the kidney as a potential therapeutic target,especially because maximal renal glucose reabsorption isincreased in T2DM. Under normal physiological conditions,nearly all filtered glucose is reabsorbed in theproximal tubule of the nephron via the sodium/glucose cotransporter2 (SGLT2). SGLT2-inhibitors are a new classof oral anti-diabetes, which reduce hyperglycemia byincreasing urinary glucose excretion independently ofinsulin secretion or action. Canagliflozin and dapagliflozinin US market, and ipragliflozin and luseogliflozin in Japanmarket are now available for glycemic control in type 2diabetics. There are several phase III clinical ongoing trialsinvolving this new class of medications. This reviewexamines some of the key efficacy and safety data fromclinical trials of the SGLT2 inhibitors approved, and theirfuture perspectives in the treatment of T2DM.

      • KCI등재

        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

        김휘승,윤태관,정창희,박중열,이우제 대한당뇨병학회 2022 Diabetes and Metabolism Journal Vol.46 No.4

        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/m<sup>2</sup>, and 11.7 years, respectively. Compared with baseline, the HbA1c decreased by 1.5% (95% confidence interval [CI], 1.27 to 1.74; <i>P</i><0.001) after 6 months and by 1.4% (95% CI, 1.19 to 1.70; <i>P</i><0.001) after 1 year. Over 1 year, the bodyweight change was −2.8 kg (95% CI, −4.21 to −1.47; <i>P</i><0.001). The combination of SGLT2i and GLP-1RA is effective and tolerable in type 2 diabetes mellitus patients in real-world practice.

      • KCI등재

        Sodium-Glucose Cotransporter-2 Inhibitor for Renal Function Preservation in Patients with Type 2 Diabetes Mellitus: A Korean Diabetes Association and Korean Society of Nephrology Consensus Statement

        오태정,문주영,허규연,고승현,김현정,김태희,이동원,문민경,The Committee of Clinical Practice Guideline,Korean Diabetes Association and Committee of the Cooperative Studies,Korean Society of Nephrology 대한당뇨병학회 2020 Diabetes and Metabolism Journal Vol.44 No.4

        Diabetes is a leading cause of end-stage renal disease. Therefore, prevention of renal dysfunction is an important treatment goal in the management of diabetes. The data of landmark cardiovascular outcome trials of sodium-glucose cotransporter-2 (SGLT2) inhibitor showed profound reno-protective effects. The Korean Diabetes Association and the Korean Society of Nephrology reviewed clinical trials and performed meta-analysis to assess the effects of SGLT2 inhibitors on the preservation of estimated glomerular filtration rate (eGFR). We limited the data of SGLT2 inhibitors which can be prescribed in Korea. Both eGFR value and its change from the baseline were significantly more preserved in the SGLT2 inhibitor treatment group compared to the control group after 156 weeks. However, some known adverse events were increased in SGLT2 inhibitor treatment, such as genital infection, diabetic ketoacidosis, and volume depletion. We recommend the long-term use SGLT2 inhibitor in patients with type 2 diabetes mellitus (T2DM) for attenuation of renal function decline. However, we cannot generalize our recommendation due to lack of long-term clinical trials testing reno-protective effects of every SGLT2 inhibitor in a broad range of patients with T2DM. This recommendation can be revised and updated after publication of several large-scale renal outcome trials.

      • KCI등재후보

        Euglycemic diabetic ketoacidosis development in a patient with type 2 diabetes receiving a sodium-glucose cotransporter-2 inhibitor and a carbohydrate-restricted diet

        고관표,Jisun Bang,Soyeon Yoo,Sang Ah Lee 제주대학교 의과학연구소 2023 The Journal of Medicine and Life Science Vol.20 No.3

        Sodium-glucose cotransporter-2 (SGLT2) inhibitors have become increasingly prescribed because of their proven protective effects on the heart and kidneys, and carbohydrate-restricted diets are popular therapeutic approaches for patients with obesity and diabetes. A 28-year-old obese woman with recently diagnosed diabetes developed euglycemic diabetic ketoacidosis (DKA) while on dapagliflozin, an SGLT2 inhibitor, and following a carbohydrate-restricted diet. She presented with nausea, vomiting, and epigastric pain. Hospital tests showed a blood glucose of 172 mg/dL, metabolic acidosis, and increased ketone levels, confirming euglycemic DKA. Treatment involved discontinuing dapagliflozin and administering fluids, glucose, and insulin. She recovered and was discharged on the fourth day. This is considered a case of euglycemic DKA induced by SGLT2 inhibitors and triggered by a carbohydrate-restricted diet. This case highlights the importance of physicians in confirming the symptoms and laboratory results of DKA, even in patients with normal blood glucose levels taking SGLT2 inhibitors and following carbohydrate-restricted diets. It is also crucial to advise patients to maintain an adequate carbohydrate intake.

      • KCI등재

        SGLT2 억제제와 만성 콩팥병

        송수현,배은희 대한내과학회 2024 대한내과학회지 Vol.99 No.2

        Chronic Kidney Disease (CKD) is a major global health burden. Sodium-glucose cotransporter-2 (SGLT2) inhibitors have demonstrated potential in slowing CKD progression. We evaluated the expanding role of SGLT2 inhibitors, emphasizing their renoprotective benefits in diabetic and non-diabetic CKD patients. We also investigated the underlying mechanisms, including the reduction of glomerular hypertension via modulation of tubuloglomerular feedback. Our study critically analyzed current indications for SGLT2 inhibitor therapy based on recent clinical trial data. To optimize patient outcomes, we present a comprehensive analysis of practical considerations for the prescription of SGLT2 inhibitors, including the potential initial decline in the estimated glomerular filtration rate and a review of adverse events.

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