1.Sodium-Glucose Cotransporter 2 Inhibitors as Emerging Anticancer Agents
Yun Kyung CHO ; Chang Hee JUNG
Diabetes & Metabolism Journal 2026;50(1):1-18
Sodium-glucose cotransporter 2 (SGLT2) inhibitors are established treatments for type 2 diabetes mellitus, heart failure, and chronic kidney disease, with well-documented metabolic and cardiorenal benefits. Emerging evidence indicates that these agents may also exert anticancer effects through mechanisms independent of glucose lowering. Preclinical studies have demonstrated functional SGLT2 expression in tumors such as prostate, pancreatic, breast, colorectal, and bone cancers. Inhibition of SGLT2 decreases tumor glucose uptake, disrupts mitochondrial respiration with subsequent adenosine monophosphate-activated protein kinase activation, and induces endoplasmic reticulum stress and autophagy. Immunomodulatory effects, including programmed death-ligand 1 (PD-L1) degradation and stimulator of interferon genes (STING)–interferon regulatory factor 3 (IRF3)–interferon-β (IFN-β) pathway activation, further illustrate their pleiotropic effects. Observational cohort studies, particularly from nationwide Korean databases, report reduced risks of pancreatic and prostate cancer among new users of SGLT2 inhibitors. In contrast, randomized controlled trials and meta-analyses focused on cardiovascular outcomes demonstrate neutral effects on overall cancer risk, providing reassurance regarding safety. Early translational studies suggest that combining SGLT2 inhibitors with chemotherapy is feasible and tolerable. In this review, we summarize the biological rationale and mechanistic insights underlying the anticancer effects of SGLT2 inhibitors, highlight preclinical and clinical evidence across different cancer types, and discuss challenges and future directions for their integration into oncology.
2.New Users of Sodium-Glucose Cotransporter 2 Inhibitors Are at Low Risk of Prostate Cancer: A Nationwide Cohort Study
Yun Kyung CHO ; Sehee KIM ; Myung Jin KIM ; Woo Je LEE ; Ye-Jee KIM ; Chang Hee JUNG
Diabetes & Metabolism Journal 2026;50(1):90-100
Background:
Preclinical studies have reported anticancer properties of sodium-glucose cotransporter 2 inhibitors (SGLT2is). We aimed to elucidate the association between the use of SGLT2is and the risk of prostate cancer among male patients with type 2 diabetes mellitus (T2DM).
Methods:
An active-comparator, new-user cohort design using a nationwide database between September 2014 and June 2020 was conducted on 45,601 new SGLT2i users and 205,395 new users of other glucose-lowering medications (oGLMs). In the following 1:1 propensity score matched (PSM) analysis, 35,371 SGLT2i users matched with an equivalent number of oGLM users were assessed. The hazard ratios (HRs) and 95% confidence intervals (CIs) for prostate cancer were calculated.
Results:
Among the cohort, prostate cancer was diagnosed in 210 out of 45,601 SGLT2i users, corresponding to a cumulative incidence of 1.0%, in contrast to 1,880 cases among 205,395 users of oGLMs, with a cumulative incidence of 1.5%. The use of SGLT2is was significantly correlated with a reduced risk of prostate cancer based on a multivariable-adjusted HR of 0.83 (95% CI, 0.71 to 0.98). PSM analysis affirmed 18% reduction in prostate cancer risk associated with SGLT2i use (HR, 0.82; 95% CI, 0.67 to 0.99). Subgroup analyses revealed that body mass index (BMI) significantly influenced the effect of SGLT2i on prostate cancer risk, with a more pronounced reduction in the subgroup with a BMI <25 kg/m2 (P=0.037).
Conclusion
The use of SGLT2is in Korean male patients with T2DM is associated with a lower risk of prostate cancer.
3.Early Onset, High Comorbidity Burden, and Regional Disparities of CADASIL:A Nationwide Cohort Study in South Korea
Ju-Yeun LEE ; Minwoo LEE ; Jae-Sung LIM ; Mi Sun OH ; Kyung-Ho YU ; Young Eun KIM ; Hyeo-Il MA ; Yun Jin KIM ; Jong Ho PARK ; Young Hee JUNG
Journal of Clinical Neurology 2026;22(2):172-182
Background:
and Purpose To compare the epidemiological and clinical features of the rare patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) with age- and sex-matched controls in a nationwide cohort from South Korea.
Methods:
This observational cohort study analyzed newly diagnosed CADASIL patients aged at least 20 years and matched controls using data from the National Health Information Database for 2004–2022. The cumulative incidence of CADASIL was assessed by age and sex, and compared between regions. Neurologic and systemic diseases were compared between the CADASIL and control groups.
Results:
The study analyzed 816 CADASIL patients and 816 age- and sex-matched controls aged 56.8±15.2 years (mean±standard deviation), among whom 48.3% were male. The cumulative incidence of CADASIL was 1.86 per 100,000 people (95% confidence interval [CI]=1.85– 1.87 per 100,000), and peaked at 60–69 years of age. In terms of regional distribution, the incidence was highest for Jeju, at 39.67 per 100,000 (95% CI 37.84–41.49 per 100,000). Neurologic diseases were more frequent in CADASIL patients, including Alzheimer’s disease (33.1% vs.20.0%), vascular dementia (84.9% vs. 5.0%), epilepsy (34.6% vs. 15.9%), stroke (70.7% vs. 27.6%), parkinsonism (18.9% vs. 11.0%), and depression (60.8% vs. 44.9%). Systemic diseases such as diabetes mellitus (78.9% vs. 68.9%) were also more common in CADASIL patients, while cancer (27.9% vs. 38.7%) and myocardial infarction (10.0% vs. 13.6%) were less common than in controls. The onset ages of all diseases were lower in CADASIL patients.
Conclusions
This study has provided a precise nationwide estimate of the CADASIL incidence and its regional distribution in South Korea. CADASIL patients showed higher incidence rates and earlier onsets of diverse clinical manifestations.
4.Engineered nutrient-stimulated hormonal multi-agonists for precision targeting of obesity and metabolic disorders
Yun Kyung CHO ; Chang Hee JUNG
Clinical and Molecular Hepatology 2026;32(2):464-486
Obesity and its related metabolic comorbidities, including type 2 diabetes, metabolic dysfunction-associated steatotic liver disease, and cardiovascular disease, are increasingly recognized as heterogeneous and multisystemic disorders. Despite the significant benefits in glycemic control and weight loss exhibited by GLP-1 receptor agonists (GLP-1RAs), their limitations have initiated the development of engineered multi-agonist therapies targeting additional nutrient-stimulated hormonal (NUSH) pathways. Dual and triple peptide-based co-agonists combining glucagon-like peptide-1 (GLP-1) with glucose-dependent insulinotropic polypeptide (GIP), glucagon, amylin, or peptide YY have demonstrated superior metabolic efficacy in preclinical and clinical studies. Tirzepatide (GLP-1/GIP dual agonist), CagriSema (GLP-1/amylin dual agonist), and retatrutide (GLP-1/GIP/glucagon triple agonist) have achieved unprecedented levels of weight loss and glycemic improvement, with certain agents also demonstrating hepatic, cardiovascular, and inflammatory benefits. Non-peptidyl oral GLP-1 RAs such as orforglipron, offer novel formulation strategies to enhance treatment accessibility and adherence. Multi-agonist incretin-based therapies represent a paradigm shift in the management of obesity and metabolic diseases. These agents offer broad clinical utility beyond glucose lowering by mimicking the pleiotropic hormonal responses observed after bariatric surgery. These therapies are poised to emerge as key components of precision metabolic medicine. This review article explores the mechanistic basis, pharmacological characteristics, and clinical data supporting the use of engineered NUSH-based peptide therapies for obesity and its related metabolic disorders, with particular emphasis on recent progress in the development and clinical application of dual and triple agonists.
5.Nationwide Trends in Coronary Artery Bypass Grafting in the Republic of Korea, 2005–2022: A Comparison with International Data
Min Ho JU ; Jun Ho LEE ; Yun Jin KIM ; Ho Jin KIM ; Ho Young HWANG ; Sang Yoon YEOM ; Hee Jung KIM ; Young-Nam YOUN ; Wook Sung KIM ; Man-Jong BAEK ; Hyun Keun CHEE ;
Journal of Chest Surgery 2026;59(1):7-16
Coronary artery bypass grafting (CABG) remains a key revascularization strategy for ischemic heart disease; however, nationwide trends in the Republic of Korea have not been thoroughly investigated. Using data from the Korean National Health Insurance Service, we analyzed adult patients who underwent isolated CABG between 2005 and 2022. We evaluated surgical volume, patient demographics, procedural strategies (off-pump vs. onpump), and outcomes. International comparisons were conducted using national cardiac surgery registry data. A total of 51,923 CABG cases were identified. Annual surgical volume declined until 2013 but gradually increased thereafter, reaching 3,717 cases in 2022. Despite this recovery, Korea’s per capita CABG rate remains among the lowest worldwide.In contrast, more than 60% of procedures were performed off-pump—the highest rate worldwide. Over time, the average patient age and prevalence of diabetes increased, whereas in-hospital mortality showed a modest decline. Compared with other countries, the Republic of Korea demonstrated a uniquely low procedural volume and a strong preference for off-pump CABG. This nationwide analysis highlights Korea’s distinctive CABG practice patterns and provides valuable insights for optimizing future clinical and policy decisions in cardiac surgical care.
6.Establishing an Active Vaccine Safety Surveillance System Using Large Scale Databases in Korea: Lessons and Scalable Insights for Global Application
Jin Gu YOON ; Eliel NHAM ; Yu Jung CHOI ; Min Joo CHOI ; Won Suk CHOI ; Young Kyung YOON ; Yu Bin SEO ; Hakjun HYUN ; Jung Yeon HEO ; Jin-Soo LEE ; Chung-Jong KIM ; Ji Yun NOH ; Joon Young SONG ; Hee Jin CHEONG
Journal of Korean Medical Science 2026;41(1):e47-
Vaccines are highly effective, but rare or delayed adverse events following immunization (AEFIs) require post-licensure surveillance beyond clinical trials. Korea lacks a comprehensive, active, database-based framework, yet key assets exist: nationwide claims databases (National Health Insurance Service/Health Insurance Review and Assessment Service), the national immunization registry (Korea Disease Control and Prevention Agency’s Immunization Registry Information System) for National Immunization Program (NIP) and non-NIP vaccines, and increasingly standardized hospital electronic health records.We propose a federated, code to data architecture with data linkages between these data.Implementation should adopt a common data model (CDM), standardized case definitions, latency accounting, and transparent public reporting under strong privacy governance. Major challenges include multi step administrative approvals for data linkage, incomplete capture of adult non-NIP vaccinations, heterogeneous hospital data structures, and strict data protection constraints. Strategic priorities are to streamline statutory and administrative processes for public health use, mandate or enable claims-based capture of adult vaccinations, enhance CDM based interoperability, and develop secure hubs for aggregated outputs. With these measures, Korea will be well positioned to establish a scalable active surveillance system capable of detecting rare AEFIs, supporting transparent and evidence-based communication, and ensuring equitable injury compensation grounded in domestic data.
7.Remission of diabetes with glutamic acid decarboxylase antibody positivity that developed after the administration of olanzapine: a case report
Kyuho KIM ; Soo Hyun SEO ; Yun Ji HONG ; Woojae MYUNG ; Bomi KIM ; Chang Ho AHN ; Sung Hee CHOI ; Hak Chul JANG ; Tae Jung OH
Precision and Future Medicine 2026;10(1):51-56
Olanzapine is a second-generation antipsychotic drug associated with the development of type 2 diabetes. However, the development and remission of diabetes with glutamic acid decarboxylase (GAD) antibody (Ab) positivity related to olanzapine treatment have not been reported. Here, we present the case of a 33-year-old man taking olanzapine who was diagnosed with diabetes with GAD Ab positivity complicated by diabetic ketoacidosis (DKA). After discontinuation of the drug and tight glycemic control, his diabetes remitted, and the GAD Ab became negative spontaneously after 18 months. The classification of diabetes is challenging because of overlapping autoimmune and metabolic features. Olanzapine may have contributed to pancreatic β-cell apoptosis, which could potentially trigger autoimmunity and the development of type 1 diabetes-like features (DKA as the initial presentation, a low C-peptide level, and GAD Ab positivity). The rapid amelioration of hyperglycemia and weight reduction may be responsible for the remission of diabetes after the discontinuation of olanzapine.
8.The Recommendation of the Neuropathic Pain Special Interesting Group of the International Association for the Study of Pain: A Comparison of Systematic Reviews and Meta-analyses between 2015 and 2025
Kyomin CHOI ; Kyung Min KIM ; Byung-Su KIM ; Hee-Jin KIM ; Seung Woo KIM ; Kyoungwon BAIK ; Jin Myoung SEOK ; Jun-Sang SUNWOO ; In-Uk SONG ; Ho Geol WOO ; Eek-Sung LEE ; Jin-Man JUNG ; Yun Ho CHOI ; Kwang Ik YANG ;
Journal of the Korean Neurological Association 2026;44(1):1-7
Neuropathic pain markedly impairs quality of life and imposes a substantial socioeconomic burden, while available treatments often provide only partial relief and are limited by safety concerns. The Neuropathic Pain Special Interest Group of the International Association for the Study of Pain (NeuPSIG-IASP) first published pharmacologic recommendations in 2007, followed by a major update in 2015 and a new guideline in 2025. This narrative review specifically compares the 2015 and 2025 NeuPSIG-IASP guidelines, outlining key methodological changes and therapeutic shifts. The 2025 guideline is based on a larger, more rigorous meta-analysis, maintains α2δ-ligands (adds mirogabalin), serotonin-noradrenaline reuptake inhibitors, and tricyclic antidepressants as first-line drugs, downgrades tramadol into the opioid third-line group. It also introduces high-frequency motor-cortex repetitive transcranial magnetic stimulation as a weakly recommended third-line option and discusses implications for Korean clinical practice.
9.Congenital Contractures of the Limbs and Face, Hypotonia, and Developmental Delay (CLIFAHDD) Associated with a De Novo Missense Variant in NALCN: The First Korean Case Report
Yoon Hee JO ; Yoo Jung LEE ; Juhyun KONG ; Yun-Jin LEE ; Sang Ook NAM ; Young Mi KIM
Annals of Child Neurology 2026;34(1):108-108
10.High-Intensity Statin Therapy and Functional Independence after Acute Ischemic Stroke in Adults Aged 75 years and Older: A Retrospective, Single-Center Cohort Study
Hyerim CHOI ; Eung-Joon LEE ; Mee Jee KIM ; Ga Hyun KIM ; Shinwoong KIM ; Namhee KIM ; Jeong Yeon SEOK ; A Jeong KIM ; Yun Hee JO ; Yoonsook CHO ; Keun-Hwa JUNG
Annals of Geriatric Medicine and Research 2026;30(2):170-179
Background:
Older patients aged ≥75 years are underrepresented in major statin trials, leaving the optimal statin intensity after acute ischemic stroke (AIS) undefined. We aimed to compare functional outcomes and short-term safety between high-intensity statin therapy (HIST) and moderate-intensity statin therapy (MIST) in patients aged ≥75 years with AIS or transient ischemic attack.
Methods:
Using a prospective stroke registry at a single tertiary center (2019–2022), we retrospectively analyzed 337 patients aged ≥75 years with AIS or transient ischemic attack who maintained statin therapy for 3 months (HIST n=117; MIST n=220). The primary outcome was a favorable 3-month functional outcome (modified Rankin Scale score 0–2). Secondary outcomes included stroke recurrence, adverse effects, and statin discontinuation. Multivariable logistic regression with pre-specified sensitivity analyses was performed.
Results:
Favorable outcomes at 3 months were more frequent with HIST (70.9% vs. 55.9%; p=0.010). After multivariable adjustment, HIST was independently associated with a favorable outcome (adjusted odds ratio [aOR]=2.03, 95% confidence interval [CI] 1.17–3.53), consistent across sensitivity analyses: per-protocol (aOR=3.48, 95% CI 1.97–6.17) and atrial fibrillation-adjusted (aOR=2.21, 95% CI 1.26–3.89). No significant differences were observed in statin discontinuation, stroke recurrence, or adverse effects.
Conclusion
In older patients with AIS, HIST was independently associated with better functional outcomes without evidence of increased harm, broadly consistent with current guideline recommendations for HIST when tolerated. Prospective studies are needed to confirm a causal relationship.

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