The TOujeo BEyond glucose control (TOBE) study evaluated clinical outcomes with insulin glargine 300 units/mL (Gla-300) in insulin-naïve Korean people with type 2 diabetes mellitus (T2DM) in a real-world setting. This 24-week, prospective, non-interventional, multicenter, open-label, single-arm, observational study included adults aged ≥ 20 years with T2DM suboptimally controlled with oral hypoglycemic agents and/or glucagon-like peptide 1 receptor agonists who require basal insulin. Eligible participants were assigned to either general target glycated hemoglobin (HbA1c < 7 Despite various efforts in managing diabetes, individuals with type 2 diabetes mellitus (T2DM) encounter numerous challenges to achieve good glycemic control. The major cause is failure to initiate insulin therapy in a timely manner, primarily because of the fear of hypoglycemia. Insulin glargine 300 units/mL (Gla-300) has smooth and prolonged activity resulting in stable and sustained glycemic control, thus reducing the risk of hypoglycemia. Studies on efficacy and safety of Gla-300 in various populations have been published globally. However, there are limited real-world studies in Asian populations. This study evaluated effectiveness and safety of Gla-300 in Korean people with T2DM who were not on insulin prior to this study but were taking oral glucose-lowering medications. The participants were assigned to two groups: general glycated hemoglobin (HbA1c) target (HbA1c < 7

Background Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator-activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined. Methods This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months. Conclusion This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D.

Introduction & Objective: The fixed ratio combination of insulin glargine and lixisenatide, iGlarLixi, was indicated as antihyperglycemic for people with T2DM and approved in November 2017 in South Korea. This post marketing surveillance (PMS) study aimed to evaluate the safety and effectiveness of iGlarLixi in clinical practice setting. Methods: This study was a multicenter, prospective, single-arm, observational study conducted in Korean people with T2DM from August 2018 to August 2023. Primary endpoint was to investigate safety profile. Secondary endpoints included changes in HbA1c, FPG and 2-hour PPG from baseline to Week 12 and 24. Results: Out of 743 people enrolled, 625 were included in safety evaluation and 519 in effectiveness evaluation. The mean age was 60.9 years and duration of T2DM was 13.6 years with equal proportions of male and female participants. Adverse events (AEs) and adverse drug reactions (ADRs) were reported in 120 (19.2%, 163 events) and 51 (8.2%, 63 events) participants, respectively. Most common AEs were gastrointestinal disorders (6.7%) such as nausea, decreased appetite, and vomiting. Significant reductions in HbA1c, FPG, 2-hour PPG were observed from baseline to Weeks 12 and 24 (Table). Conclusion: In clinical practice, iGlarLixi has shown to be safe and well tolerated without new safety concerns improving clinical outcomes in people with T2DM in South Korea. Disclosure H. Kim: None. K. Min: None. S. Kim: None. E. Kim: None. Y. Chung: None. C.H. Chung: None. J. Yun: None. W. Kim: None. D. Kim: Employee; Sanofi, GlaxoSmithKline plc. S. Yoo: None. Funding Sanofi

Despite a plethora of clinical trials to develop effective pharmacotherapy against nonalcoholic steatohepatitis (NASH), there is no drug approved to meet this purpose due to uncertainty about best targets for NASH. Glucagonlike peptide1 receptor agonists (GLP1 RAs) focus on the extrahepatic milieu with pleiotropic effects on multiple metabolic organs, since GLP1 R is abundantly expressed in the pancreas, brain, heart, kidney and gut rather than in the liver.1 GLP1 RAs protect islet β cells, suppress appetite, improve cardiac and renal function and delay gastric emptying, leading to body weight loss.2 Consequently, GLP1 RAs are widely used in the treatment of type 2 diabetes mellitus and obesity. Flint et al. have published the results of a phase I trial of 72week daily subutaneous (sc) semaglutide, a GLP1 RA, on liver stiffness and fat quantified, respectively, by magnetic resonance elastography (MRE) and magnetic resonance imaging proton density fat fraction.3 Unfortunately, they failed to hit the primary endpoint (liver stiffness), but showed significant antisteatotic efficacy, which was in line with the recent phase II (sc daily) trial for biopsyproven NASH.4 Based on these results, a phase III (sc weekly) trial has recently been initiated. The strength was the use of noninvasive imaging biomarkers instead of liver biopsy as surrogate endpoints to evaluate changes in fibrosis and steatosis. In realworld settings, noninvasive biomarkers are more clinically relevant to patients with NASH than histological changes in terms of monitoring treatment response. Accumulating evidence has shown that changes in imaging biomarkers are highly correlated with histological changes.57 Multiparametric approaches have been developed to improve the noninvasive identification of highrisk NASH. A strategy combining two biomarkers into one index with single cutoffs for each, such as FibroscanAST (FAST) and MRE plus FIB4 (MEFIB), provides high diagnostic performance for highrisk NASH.810 It would be interesting to assess longitudinal changes in FAST or MEFIB with histological changes in the future NASH clinical trials. The drawback was that this trial was underpowered because of the small sample size with advanced fibrosis (15%), which might explain the failure to capture significant changes in liver stiffness. In addition, the predefined treatment duration of 72 weeks seemed to be insufficient to fulfil the primary endpoint, which was also confirmed by the phase II trial.4 It remains unclear whether the antisteatotic efficacy of semaglutide is a direct effect or an indirect effect mediated by weight loss. A mediation analysis to assess the extent to which changes in liver steatosis and stiffness are mediated via weight loss is needed to determine the causation/mediation. This trial demonstrates the metabolically beneficial effects of semaglutide in western NAFLD populations, who are mostly obese. However, it is unclear whether such effects would also be valid in relatively nonobese Asian populations who are rarely investigated in the setting of clinical trials.11 Moreover, nondiabetic NAFLD patients remain an uncertain target population for GLP1 RA treatment. In the future, more evidence will be needed for GLP1based therapies in the fight against advanced NASH despite their beneficial effects.

Background Seizure can be triggered by the non-ketotic hyperglycemia (NKH). Recently we analysed 18 cases of NKH induced seizure to identify the causes for NKH, seizure types, prognosis, and the differences of clinical presentation between the patient with chronic brain structural lesion (CBSL) and the patient without. Methods Eighteen patients with NKH induced seizure were selected from the database. Data regarding brain images, clinical symptoms, co-morbid illnesses, blood laboratories, and prognosis were collected. Patients were divided into two groups according to the presence of CBSL. Results The patients with CBSL showed more generalized tonic-clonic seizure (GTCS) than without. Focal seizures in this group appeared to be originated from the pre-existing lesion in many situations. The poor compliance to anti-diabetic treatment and physical stresses were most common causes for NKH. One year seizure remission without anti-epileptic drug treatment was achieved in 17 of 18 patients. Conclusions The patients with CBSL might have more GTCS than without. The impairment of inhibitory mechanism surrounding the focal irritative zone might be one of plausible explanation for this phenomenon. The prognosis was favorable. Further large studies are required. Key Words: Non-ketotic hyperglycemia, Seizure, Brain lesion, Generalized tonic-clonic seizure, Prognosis

The proportions of people with type 2 diabetes and obesity have increased throughout Asia, and the rate of increase shows no sign of slowing. People in Asia tend to develop diabetes with a lesser degree of obesity at younger ages, suffer longer with complications of diabetes, and die sooner than people in other regions. Childhood obesity has increased substantially and the prevalence of type 2 diabetes has now reached epidemic levels in Asia. The health consequences of this epidemic threaten to overwhelm health-care systems in the region. Urgent action is needed, and advocacy for lifestyle changes is the first step. Countries should review and implement interventions, and take a comprehensive and integrated public-health approach. At the level of primary prevention, such programmes can be linked to other non-communicable disease prevention programmes that target lifestyle-related issues. The cost of inaction is clear and unacceptable.