• 고신대학교 의과대학 학술지
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• 제33권3호
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• pp.402-408
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• 2018

Inhibitors of sodium-glucose cotransporters type 2 (SGLT2) are proposed as a novel approach for the management of type 2 diabetes mellitus. SGLT2 cotransporters are responsible for reabsorption of 90 % of the glucose filtered by the kidney. The glucuretic effect resulting from SGLT2 inhibition contributes to reduce hyperglycaemia and also assists weight loss and blood pressure reduction. In this study, we presented the case of a 59-year-old male who developed hyperosmolar hyperglycemic state (HHS), possibly caused by a sodium-glucose cotransporter 2 (SGLT2) inhibitor, a novel class of antihyperglycemic agents. This case highlights that HHS can develop in patients with diabetes treated with SGLT2 inhibitors.

• 당뇨병
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• 제19권3호
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• pp.135-139
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• 2018

The sodium-glucose cotransporter-2 inhibitor (SGLT2i) is a new anti-hyperglycemic agent that have function to concomitantly inhibit the reabsorption of glucose and sodium in the renal proximal convoluting tubule. Recent two cardiovascular outcome trials showed that a lower risk of cardiovascular events with SGLT2i in people with type 2 diabetes. In addition, prior real-world data demonstrated similar SGLT2i effects, but these studies were limited to the United States and Europe. Thus, the CVD-REAL (Comparative Effectiveness of Cardiovascular Outcomes in New Users of Sodium-Glucose Cotransporter-2 Inhibitors) 2 Study was investigated cardiovascular outcomes in those initiated on SGLT2i versus other glucose-lowering drugs (oGLDs) across 6 countries in the Asia Pacific, the Middle East, and North American regions. In Korea, 336,644 episodes of initiation in SGLT2i or oGLD group between September 2014 and December 2016 were identified in Korea National Health Insurance database after propensity score matching. SGLT2i users was associated with a lower risk of all-cause death (hazard ratio [HR], 0.72; 95% confidence interval [CI], 0.67~0.77), hospitalization for heart failure (HHF) (HR, 0.87; 95% CI, 0.82~0.92), all-cause death or HHF (HR, 0.81; 95% CI, 0.78~0.85), myocardial infarction (HR, 0.81; 95% CI, 0.74~0.89), and stroke (HR, 0.82; 95% CI, 0.78~0.86) compared with oGLD users. In conclusion, initiation of SGLT2i had a lower risk of cardiovascular events in people with type 2 diabetes compared with oGLDs.

• Journal of Medicine and Life Science
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• 제20권3호
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• pp.126-130
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• 2023

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.

• 한국임상약학회지
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• 제27권4호
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• pp.214-220
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• 2017

Background: Dapagliflozin is an oral selective inhibitor of sodium-glucose cotransporter 2(SGLT2), the kidney transporter chiefly responsible for glucose reabsorption from the glomerular filtrate. Because this mechanism does not require the action of insulin, dapagliflozin rarely causes hypoglycemia. Dapagliflozin may affect blood glucose control as well as blood pressure and the body weight which are one of the cardiovascular disease risk factors. However, dehydration and ketoacidosis are reported as the side effects of the dapagliflozin treatment and the safety issues have been occurred. The aim of this study is to analyze the effectiveness and adverse events of dapagliflozin in Korean patients. Methods: From December 2014 to August 2015, we retrospectively reviewed the electronic medical records of type 2 diabetes patients who were prescribed dapagliflozin at Severance Hospital. Results: A total of 202 Korean patients were enrolled in this study. The effectiveness in the reduction of blood glucose was statistically significant(p<0.001). Dapagliflozin decreased 0.74% of HbA1c after 24 weeks. Significantly more participants achieved the target HbA1c level(HbA1c<7%) after 24 weeks(n=42, 35.3%) than before taking dapagliflozin(n=21, 17.6%). Blood pressure decreased 5.7 mmHg systolic blood pressure(SBP), 1.9 mmHg diastolic blood pressure(DBP) after 24 weeks. More than one quarter of participants(n=35, 29.4%) experienced weight loss. Most common adverse event was genitourinary symptoms. Conclusion: In this study, the effectiveness of dapagliflozin in improving glycemic control, blood pressure control, and weight loss was statistically significant. However, elderly and female patients, who have higher incidence of adverse events, should use dapagliflozin cautiously.

• The Korean Journal of Physiology and Pharmacology
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• 제5권2호
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• pp.183-188
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• 2001

To elucidate antidiabetic effect and mechanism(s) of acarbose in a polygenic spontaneous hyperglycemic and hyperinsulinemic diabetic animal model, $KKA^y$ mice, acarbose was administered orally for 4 weeks and effects on body weight, plasma glucose and insulin levels, genetic expressions of intestinal sucrase-isomaltase (SI), sodium-glucose cotransporter (sGLT1) and glucose transporter in quadriceps muscle (GLUT4) were examined in this study. Although no differences in body weight were detected between control and acarbose-treated groups, plasma glucose level in acarbose-treated group was markedly reduced as compared to the control. In the mechanism study, acarbose downregulated the SI and SGLT1 gene expressions, and upregulated the GLUT4 mRNA and protein expressions when compared to the control group. In conclusion, the data obtained strongly implicate that acarbose can prevent the hyperglycemia in $KKA^y$ mice possibly through blocking intestinal glucose absorption by downregulations of SI and sGLT1 mRNA expressions, and upregulation of skeletal muscle GLUT4 mRNA and protein expressions.

• 한국임상약학회지
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• 제32권1호
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• pp.13-19
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• 2022

Background: The use of combination therapy and fixed-dose combination therapy is increasing for the treatment of type 2 diabetes. Sodium glucose cotransporter-2 inhibitor (SGLT2i) is a drug class used in combination with metformin. Methods: Type 2 diabetes patients on SGLT2i/metformin combination therapy were extracted from the 2019 Health Insurance Review & Assessment Service-National Patients Sample. On July 1, 2019, SGLT2i and metformin fixed-dose combination (SGLT2i/metformin FDC) and two-pill combination (TPC) groups were identified, and a chi-square test and multiple logistic regression were performed. Results: Of total 2,992 patients, 1,077 (36%) were prescribed SGLT2i/metformin FDC and 1,915 (64%) were prescribed TPC. We found that the most common comorbidities were in the order of dyslipidemia, gastrointestinal disease, and hypertension. Multiple logistic regression analysis showed that the use of SGLT2i/metformin FDC was lower than TPC in patients with diabetic neuropathy (OR=0.76, p=0.008). Clinic (OR=2.09, p<0.001) and general hospital (OR=1.40, p=0.019) showed higher tendency to prescribe SGLT2i/metformin FDC compared to tertiary hospital. The tendency of prescribing SGLT2i/metformin FDC was lower in Kyeonggi (OR=0.79, p=0.037), Gyeongsang (OR=0.77, p=0.025) and Chungcheong (OR=0.68, p=0.007) than Seoul. Conclusion: Factors related to the use of SGLT2i/metformin FDC in patients with type 2 diabetes were complication, medical institution and region. The tendency to prescribe SGLT2i/metformin FDC was relatively higher in clinics than in tertiary general hospitals and in Seoul than in other regions.

• Reproductive and Developmental Biology
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• 제33권4호
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• pp.211-216
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• 2009

A cell frequently utilizes glucose as a fuel of energy and a major substrate of lipid and protein syntheses. A regulation of glucose movement into and out of the cells is precisely controlled by cooperative works of passive and sodium-dependent active processes. At least 13 glucose cotransporter (Slc2a, GLUT) isoforms involve in passive movement of glucose in cells. The efferent ductules (EDs) play in a number of important functions for maintenance of male fertility. In the present study, using real-time PCR analysis, we determined gene expression of five Slc2a isoforms in the EDs. In addition, we compared expression levels of these Slc2a isoforms according to postnatal development ages, 1 week, 2 weeks, 1 month, and 3 months. Results from the current study showed that expression of Slc2a1, Slc2a3, and Slc2a5 mRNAs reached the highest levels at 1 month of age, followed by a transient decrease at 3 months of age. In addition, the level of Slc2a4 mRNA reminded at steady until 1 month of age and was significantly reduced at 3 months of age, whereas the highest level of Slc2a 8 mRNA was detected at 2 weeks of age. Data from the present study indicate a differential expression of various Slc2a isoforms in the ED according to postnatal ages. Thus, it is believed that glucose movement through the epithelial cells in the ED would be regulated by the coordinated manner among Slc2a isoforms expressed at a given age.

• The Korean Journal of Physiology and Pharmacology
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• 제27권3호
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• pp.221-230
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• 2023

Diabetic kidney disease is one of the most serious complications of diabetes. Although diabetic kidney disease can be effectively controlled through strict blood glucose management and corresponding symptomatic treatment, these therapies cannot reduce its incidence in diabetic patients. The sodium-glucose cotransporter 2 (SGLT2) inhibitors and the traditional Chinese herb "Gegen" have been widely used in diabetes-related therapy. However, it remains unclear whether the combined use of these two kinds of medicines contributes to an increased curative effect on diabetic kidney disease. In this study, we examined this issue by evaluating the efficacy of the combination of puerarin, an active ingredient of Gegen, and canagliflozin, an SGLT2 inhibitor for a 12-week intervention using a mouse model of diabetes. The results indicated that the combination of puerarin and canagliflozin was superior to canagliflozin alone in improving the metabolic and renal function parameters of diabetic mice. Our findings suggested that the renoprotective effect of combined puerarin and canagliflozin in diabetic mice was achieved by reducing renal lipid accumulation. This study provides a new strategy for the clinical prevention and treatment of diabetic kidney disease. The puerarin and SGLT2 inhibitor combination therapy at the initial stage of diabetes may effectively delay the occurrence of diabetic kidney injury, and significantly alleviate the burden of renal lipotoxicity.

• The Korean Journal of Physiology and Pharmacology
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• 제23권1호
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• pp.55-62
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• 2019

HM41322 is a novel oral sodium-glucose cotransporter (SGLT) 1/2 dual inhibitor. In this study, the in vitro and in vivo pharmacokinetic and pharmacologic profiles of HM41322 were compared to those of dapagliflozin. HM41322 showed a 10-fold selectivity for SGLT2 over SGLT1. HM41322 showed an inhibitory effect on SGLT2 similar to dapagliflozin, but showed a more potent inhibitory effect on SGLT1 than dapagliflozin. The maximum plasma HM41322 level after single oral doses at 0.1, 1, and 3 mg/kg were 142, 439, and 1830 ng/ml, respectively, and the $T_{1/2}$ was 3.1 h. HM41322 was rapidly absorbed and reached the circulation within 15 min. HM41322 maximized urinary glucose excretion by inhibiting both SGLT1 and SGLT2 in the kidney. HM41322 3 mg/kg caused the maximum urinary glucose excretion in normoglycemic mice ($19.32{\pm}1.16mg/g$) at 24 h. In normal and diabetic mice, HM41322 significantly reduced glucose excursion. Four-week administration of HM41322 in db/db mice reduced HbA1c in a dose dependent manner. Taken together, HM41322 showed a favorable preclinical profile of postprandial glucose control through dual inhibitory activities against SGLT1 and SGLT2.

• Journal of Veterinary Science
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• 제23권5호
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• pp.76.1-76.14
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• 2022

Background: Clinical dexamethasone (DEX) treatment or stress in bovines results in extensive physiological changes with prominent hyperglycemia and neutrophils dysfunction. Objectives: To elucidate the effects of DEX treatment in vivo on cellular energy status and the underlying mechanism in circulating neutrophils. Methods: We selected eight-month-old male bovines and injected DEX for 3 consecutive days (1 time/d). The levels of glucose, total protein (TP), total cholesterol (TC), and the proinflammatory cytokines interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α in blood were examined, and we then detected glycogen and adenosine triphosphate (ATP) content, phosphofructosekinase-1 (PFK1) and glucose-6-phosphate dehydrogenase (G6PDH) activity, glucose transporter (GLUT)1, GLUT4, sodium/glucose cotransporter (SGLT)1 and citrate synthase (CS) protein expression and autophagy levels in circulating neutrophils. Results: DEX injection markedly increased blood glucose, TP and TC levels, the Ca²⁺/P⁵⁺ ratio and the neutrophil/lymphocyte ratio and significantly decreased blood IL-1β, IL-6 and TNF-α levels. Particularly in neutrophils, DEX injection inhibited p65-NFκB activation and elevated glycogen and ATP contents and SGLT1, GLUT1 and GR expression while inhibiting PFK1 activity, enhancing G6PDH activity and CS expression and lowering cell autophagy levels. Conclusions: DEX induced neutrophils glucose uptake by enhancing SGLT1 and GLUT1 expression and the transformation of energy metabolism from glycolysis to pentose phosphate pathway (PPP)-tricarboxylic acid (TCA) cycle. This finding gives us a new perspective on deeper understanding of clinical anti-inflammatory effects of DEX on bovine.