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.

The Committee of Clinical Practice Guidelines of the Korean Diabetes Association (KDA) updated the previous clinical practice guidelines for Korean adults with diabetes and prediabetes and published the seventh edition in May 2021. We performed a comprehensive systematic review of recent clinical trials and evidence that could be applicable in real-world practice and suitable for the Korean population. The guideline is provided for all healthcare providers including physicians, diabetes experts, and certified diabetes educators across the country who manage patients with diabetes or the individuals at the risk of developing diabetes mellitus. The recommendations for screening diabetes and glucose-lowering agents have been revised and updated. New sections for continuous glucose monitoring, insulin pump use, and non-alcoholic fatty liver disease in patients with diabetes mellitus have been added. The KDA recommends active vaccination for coronavirus disease 2019 in patients with diabetes during the pandemic. An abridgement that contains practical information for patient education and systematic management in the clinic was published separately.

The Committee of Clinical Practice Guidelines of the Korean Diabetes Association (KDA) updated the previous clinical practice guidelines for Korean adults with diabetes and prediabetes and published the seventh edition in May 2021. We performed a comprehensive systematic review of recent clinical trials and evidence that could be applicable in real-world practice and suitable for the Korean population. The guideline is provided for all healthcare providers including physicians, diabetes experts, and certified diabetes educators across the country who manage patients with diabetes or the individuals at the risk of developing diabetes mellitus. The recommendations for screening diabetes and glucose-lowering agents have been revised and updated. New sections for continuous glucose monitoring, insulin pump use, and non-alcoholic fatty liver disease in patients with diabetes mellitus have been added. The KDA recommends active vaccination for coronavirus disease 2019 in patients with diabetes during the pandemic. An abridgement that contains practical information for patient education and systematic management in the clinic was published separately.

BACKGROUND: Combination of metformin to reduce the fasting plasma glucose level and an α-glucosidase inhibitor to decrease the postprandial glucose level is expected to generate a complementary effect. We compared the efficacy and safety of a fixed-dose combination of voglibose plus metformin (vogmet) with metformin monotherapy in drug-naïve newly-diagnosed type 2 diabetes mellitus. METHODS: A total of 187 eligible patients aged 20 to 70 years, with a glycosylated hemoglobin (HbA1c) level of 7.0% to 11.0%, were randomized into either vogmet or metformin treatments for 24 weeks. A change in the HbA1c level from baseline was measured at week 24. RESULTS: The reduction in the levels of HbA1c was −1.62%±0.07% in the vogmet group and −1.31%±0.07% in the metformin group (P=0.003), and significantly more vogmet-treated patients achieved the target HbA1c levels of <6.5% (P=0.002) or <7% (P=0.039). Glycemic variability was also significantly improved with vogmet treatment, estimated by M-values (P=0.004). Gastrointestinal adverse events and hypoglycemia (%) were numerically lower in the vogmet-treated group. Moreover, a significant weight loss was observed with vogmet treatment compared with metformin (−1.63 kg vs. −0.86 kg, P=0.039). CONCLUSION: Vogmet is a safe antihyperglycemic agent that controls blood glucose level effectively, yields weight loss, and is superior to metformin in terms of various key glycemic parameters without increasing the risk of hypoglycemia.
Blood Glucose ; Diabetes Mellitus, Type 2 ; Fasting ; Glucose ; Hemoglobin A, Glycosylated ; Humans ; Hypoglycemia ; Metformin ; Weight Loss

PURPOSE: Upper gastrointestinal bleeding (UGIB) is one of the most common causes of emergency department (ED) presentation which can lead to a fatal condition. Many clinical scoring systems intended to predict the prognosis of UGIB patients were developed and validated, including Glasgow-Blatchford score (GBS) and Rockall score (RS). In particular, GBS has shown its superiority in prediction of mortality, the necessity of endoscopic intervention and admission, compared with other scoring systems, in recent studies. However, GBS does not include the age of the patient as its component and has clearly shown its efficacy only in subjects under age 70. Hence, we aimed to assess whether GBS could also be used in old age UGIB patients as a useful risk stratifying method as in younger age. METHODS: UGIB patients who visited our ED for one year were retrospectively enrolled in the analysis. Medical records of the subjects were reviewed, and their GBS and clinical RS were calculated. Receiver-operating characteristics (ROC) curve of each score in prediction of high risk UGIB was drawn and area under curve (AUC) was calculated. Correlation analysis of each score and hospital length of stay was also performed. To assess the validity of each score for use in old age patients, all analyses were also performed in subgroups of age over 60 years, and under that. RESULTS: ROC curves suggest that GBS has significant detecting power for high risk UGIB in overall subjects, subgroups of age over 60 and under (p=<0.001 for all, AUC=0.919, 0.935, 0.901, respectively). Otherwise, clinical RS only showed significant results in overall group and subgroup of age over 60 with lower AUC. CONCLUSION: GBS may also be used safely as an initial risk stratifying method in old age UGIB patients visiting the ED, as in other age groups.
Area Under Curve ; Emergency Service, Hospital* ; Gastrointestinal Hemorrhage ; Geriatric Assessment ; Hemorrhage* ; Humans ; Length of Stay ; Medical Records ; Mortality ; Patient Acuity ; Prognosis ; Retrospective Studies ; ROC Curve

Here, we show that radicicol, a fungal antibiotic, resulted in marked inhibition of inducible nitric oxide synthase (iNOS) transcription by the pancreatic beta cell line MIN6N8a in response to cytokine mixture (CM: TNF-alpha, IFN-gamma, and IL-1beta). Treatment of MIN6N8a cells with radicicol inhibited CM-stimulated activation of NF-kappaB/Rel, which plays a critical role in iNOS transcription, in a dose-related manner. Nitrite production in the presence of PD98059, a specific inhibitor of the extracellular signal-regulated protein kinase-1 and 2 (ERK1/2) pathway, was dramatically diminished, suggesting that the ERK1/2 pathway is involved in CM-induced iNOS expression. In contrast, SB203580, a specific inhibitor of p38, had no effect on nitrite generation. Collectively, this series of experiments indicates that radicicol inhibits iNOS gene expression by blocking ERK1/2 signaling. Due to the critical role that NO release plays in mediating destruction of pancreatic beta cells, the inhibitory effects of radicicol on iNOS expression suggest that radicicol may represent a useful anti-diabetic activity.
Flavonoids ; Gene Expression ; Imidazoles ; Insulin-Secreting Cells ; Macrolides ; Negotiating ; Nitric Oxide Synthase Type II ; Pyridines ; Tumor Necrosis Factor-alpha

BACKGROUND AND OBJECTIVES: The growing implantations of electrophysiological devices in the context of increasing rates of chronic antithrombotic therapy in cardiovascular disease patients underscore the importance of an effective periprocedural prophylactic strategy for prevention of bleeding complications. We assessed the risk of significant bleeding complications in patients receiving anti-platelet agents or anticoagulants at the time of permanent pacemaker (PPM) implantation. SUBJECTS AND METHODS: We reviewed bleeding complications in patients undergoing PPM implantation. The use of aspirin or clopidogrel was defined as having taking drugs within 5 days of the procedure and warfarin was changed to heparin before the procedure. A significant bleeding complication was defined as a bleeding incident requiring pocket exploration or blood transfusion. RESULTS: Permanent pacemaker implantations were performed in 164 men and 96 women. The mean patient age was 73+/-11 years old. Among the 260 patients, 14 patients took warfarin (in all of them, warfarin was changed to heparin at least 3 days before procedure), 54 patients took aspirin, 4 patients took clopidogrel, and 25 patients took both. Significant bleeding complications occurred in 8 patients (3.1%), all of them were patients with heparin bridging (p<0.0001). Heparin bridging markedly increased the length of required hospital stay when compare with other groups and the 4 patients (1.5%) that underwent the pocket revision for treatment of hematoma. CONCLUSION: This study suggests that hematoma formation after PPM implantation was rare, even among those who had taken the anti-platelet agents. The significant bleeding complications frequently occurred in patients with heparin bridging therapy. Therefore, heparin bridging therapy was deemed as high risk for significant bleeding complication in PPM implantation.
Anticoagulants ; Aspirin ; Cardiovascular Diseases ; Female ; Hematoma ; Hemorrhage ; Heparin ; Humans ; Length of Stay ; Male ; Ticlopidine ; Warfarin

OBJECTIVES: Cognitive behavioral therapy and social skills training have been proposed as a promising modality for treatment of patients with schizophrenia. The objective of this study was to evaluate the effectiveness of Cognitive Behavioral Social Skill Training (CBSST) in patients with chronic schizophrenia. METHODS: Twenty six middle- or older-aged hospitalized patients with schizophrenia were selected in a mental hospital. Eleven participants were randomly assigned to undergo treatment with CBSST and 15 participants were assigned to receive the usual treatment. CBSST was administered in a single group over 12 sessions for a period of weeks, and the participants were assessed by blinded raters at base line and end point, and end of treatment. RESULTS: Compared to patients who received the usual treatment, those who received treatment with CBSST showed a significant reduction of Hamilton Rating Scale for Depression score, however, scores for other psychiatric symptoms did not differ significantly. In terms of Quality of life (QoL) analysis, scores for overall quality of life showed a more significant increase in the CBSST group, compared with the group of patients who received the usual treatment. According to results of the Independent Living Skill Survey, patients receiving CBSST showed significantly greater involvement in social activities than patients receiving usual treatment group. CONCLUSION: Psychosocial intervention for patients with chronic schizophrenia is very important, not only for management of primary psychiatric symptoms, but also for QoL and social rehabilitation. The results of this study, showing improvement of depressive mood, overall life quality, and social activities, suggest that CBSST could be an effective treatment for these patients. This study is a pilot study performed in an inpatient treatment setting. Further studies are required in order to clarify the advantage of CBSST in treatment of patients with chronic schizophrenia, esp. under outpatient settings.
Cognitive Therapy ; Depression ; Hospitals, Psychiatric ; Humans ; Imidazoles ; Independent Living ; Inpatients ; Nitro Compounds ; Outpatients ; Pilot Projects ; Quality of Life ; Schizophrenia

BACKGROUND/AIMS: The aim of this study was to identify changes in left ventricular (LV) performance in patients with a myocardial bridge (MB) in the left anterior descending coronary artery during resting and in an inotropic state. METHODS: Myocardial strain measurement by speckle-tracking echocardiography and conventional LV wall-motion scoring was performed in 18 patients with MB (mean age, 48.1 +/- 1.7 years, eight female) during resting and intravenous dobutamine challenge (10 and 20 microg/kg/min). RESULTS: Conventional LV wall-motion scoring was normal in all patients during resting and in an inotropic state. Peak regional circumferential strain increased dose dependently upon dobutamine challenge. Longitudinal strains of the anterior and anteroseptal segments were, however, reduced at 20 microg/kg/min and showed a dyssynchronous pattern at 20 microg/kg/min. Although there were no significant differences in radial strain and displacement of all segments at rest compared with under 10 microg/kg/min challenge, radial strain and displacement of anterior segments at 20 microg/kg/min were significantly reduced compared with posterior segments at the papillary muscle level (44.8 +/- 14.9% vs. 78.4 +/- 20.1% and 5.3 +/- 2.3 mm vs. 8.5 +/- 1.8 mm, respectively; all p < 0.001), and showed plateau (40%) or biphasic (62%) patterns. CONCLUSIONS: Reduced LV strain of patients with MB after inotropic stimulation was identified. Speckle-tracking strain echocardiography identified a LV myocardial dyssynchrony that was not demonstrated by conventional echocardiography in patients with MB.
Adrenergic beta-1 Receptor Agonists/*diagnostic use ; Adult ; Aged ; Chest Pain ; Coronary Angiography ; Diastole ; Dobutamine/*diagnostic use ; Echocardiography, Stress/instrumentation/*methods ; Female ; Humans ; Male ; Middle Aged ; *Myocardial Contraction ; *Myocardium ; Physical Exertion ; Systole ; *Ventricular Dysfunction, Left ; Ventricular Function, Left/*drug effects