Background: We assessed the efficacy and safety of enavogliflozin (0.3 mg), a newly developed SGLT-2 inhibitor, in patients with type 2 diabetes mellitus based on kidney function via pooled analysis of two 24-week, randomized, double-blind phase III trials. Methods: Data from 470 patients were included (enavogliflozin: 0.3 mg/day, n = 235; dapagliflozin: 10 mg/day, n = 235). The subjects were classified by mildly reduced (60 ≤ eGFR < 90 mL/min/1.73 m², n = 247) or normal eGFR (≥ 90 mL/min/1.73 m², n = 223). Results: In the mildly reduced eGFR group, enavogliflozin significantly reduced the adjusted mean change of HbA1c and fasting plasma glucose levels at week 24 compared to dapagliflozin (− 0.94% vs. −0.77%, P = 0.0196). Enavogliflozin exhibited a more pronounced glucose-lowering effect by HbA1c when combined with dipeptidyl peptidase-4 inhibitors than that observed in their absence. Enavogliflozin showed potent blood glucose-lowering effects regardless of renal function. Conversely, dapagliflozin showed a significant decrease in the glucose-lowering efficacy as the renal function decreased. Enavogliflozin showed a higher urinary glucose excretion rate in both groups. The homeostatic model assessment showed that enavogliflozin markedly decreased the insulin resistance. The blood pressure, weight loss, or homeostasis model assessment of beta-cell function values did not differ significantly between enavogliflozin and dapagliflozin. Adverse events were similar between both drugs. Conclusions: The glucose-lowering efficacy of enavogliflozin is superior to that of dapagliflozin in patients with type 2 diabetes mellitus with mild renal function impairment; this is attributed to its potent urinary glucose excretion-promoting ability. The emergence of new and potent SGLT-2 inhibitors is considered an attractive option for patients with inadequate glycemic control and decreased renal function. Trial registration: Not applicable (pooled analysis).

Background: Extended-spectrum β-lactamase (ESBL)–producing Enterobacterales are an increasing cause of complicated urinary tract infections (UTIs). Reliance on carbapenems to treat these infections accelerates resistance, underscoring the urgent need for effective oral transition options to preserve last-line agents and lessen healthcare burden. Methods: We conducted a multicenter, open-label, randomized, noninferiority trial at four tertiary hospitals in South Korea (November 2022–June 2025). Adults hospitalized with complicated UTIs due to ESBL-producing Enterobacterales who improved after 3–7 days of intravenous antibiotics were randomized (1:1) to either continue intravenous carbapenem or β-lactam/β-lactamase inhibitor therapy or switch to oral fosfomycin trometamol (3 g once daily). The primary outcome was clinical cure, defined as resolution of urinary tract infection–related symptoms and signs within 4 days after completion of treatment. Secondary outcomes included microbiological cure, readmission, adverse events, and 30-day recurrence. Results: Of the 344 screened patients, 299 were randomized (152 oral fosfomycin; 147 intravenous therapy). Clinical cure occurred in 92.8% of the oral fosfomycin group and 95.2% of the intravenous group (risk difference, −2.47%; 95% CI −7.84 to 2.89), confirming noninferiority. Microbiological cure was similarly high in both groups: urine (98.0% vs 96.6%) and blood (97.3% vs 97.5%). Safety profiles and 30-day outcomes were also comparable. Conclusions: Oral fosfomycin was noninferior to continued intravenous therapy when used as oral transition therapy for complicated UTIs caused by ESBL-producing Enterobacterales. These findings provide evidence to support oral fosfomycin transition as a carbapenem-sparing antibiotic stewardship strategy for patients with complicated UTIs caused by ESBL-producing Enterobacterales. Clinical Trials Registration: KCT0007669.

Purpose: To investigate the safety and effectiveness of naltrexone-bupropion in Korean adults with obesity. Patients and methods: This was a prospective, observational multicenter study from April 29, 2016, to April 28, 2022. Individuals with obesity with a body mass index of ≥ 30 kg/m² or ≥ 27 kg/m² who had obesity-related comorbidities were included. The naltrexone-bupropion dose was gradually titrated weekly from 8/90 to 32/360 mg and maintained at the maximum tolerated dose. In total, 612 and 300 individuals were evaluated for safety and effectiveness, respectively. Results: In total, 41.34% individuals reported drug-related adverse reactions, such as nausea (19.12%), headache (7.68%), and dizziness (5.23%). Older age and comorbidities were significantly associated with adverse events. At 12 weeks after reaching the maintenance dose, naltrexone-bupropion 32/360 mg resulted in the greatest weight reduction (− 7.21%) compared with other doses, which persisted at week 24 (− 7.69%). The naltrexone-bupropion 16/180 mg resulted in significant weight reduction, achieving − 5.99% and − 9.18% reductions at weeks 12 and 24, similar to that with naltrexone-bupropion 32/360 mg. Young age and no comorbidities were significantly associated > 5% weight reduction. Conclusion: Naltrexone-bupropion demonstrated marked stability and weight loss effectiveness, particularly in young individuals with obesity without comorbidities. Therefore, individualized treatment is necessary when prescribing naltrexone-bupropion.

Background: Sodium–glucose cotransporter-2 (SGLT2) inhibitors are widely used to manage type 2 diabetes mellitus (T2DM) because of their glucose-lowering and cardioprotective effects. However, euglycemic diabetic ketoacidosis (euDKA) is an uncommon but serious adverse event. EuDKA is characterized by metabolic acidosis and ketosis with only mild-to-moderate hyperglycemia, making diagnosis challenging. The risk of this interaction may be increased with the concurrent use of glucagon-like peptide-1 receptor agonists (GLP-1RAs), particularly during periods of reduced caloric intake or the presence of gastrointestinal symptoms. Case: A 38-year-old woman with newly diagnosed T2DM presented with five days of fatigue, poor oral intake, nausea, and vomiting. She had recently initiated semaglutide (GLP-1RA) for weight loss and practiced prolonged intermittent fasting. One week prior, she had started metformin and enavogliflozin, a selective SGLT2 inhibitor. Laboratory results showed a glucose level of 137 mg/dL, urine ketones (+++), lactate level of 4.87 mg/dL, HbA1c of 9.3%, C-peptide of 0.88 ng/mL, and high anion gap metabolic acidosis. She was diagnosed with euDKA and treated with IV fluids, insulin infusion, dextrose, and potassium supplementation. Her symptoms resolved, and she was discharged in a stable condition. Conclusion: This case highlights the importance of recognizing euDKA in patients using SGLT2 inhibitors and GLP-1RAs, particularly those with fasting or gastrointestinal symptoms. Clinicians should suspect euDKA even without significant hyperglycemia to enable prompt diagnosis and management, thereby preventing complications.

The metabolic benefits of sodium-glucose co-transporter 2 inhibitors in clinical application are well established; however, there is dearth of knowledge on their impact on adipokine regulation. This study investigated the effect of enavogliflozin on adiponectin and leptin in patients with type 2 diabetes. This secondary analysis of a phase III randomized, double-blind, placebo-controlled trial evaluated changes in serum adiponectin and leptin over 24 weeks. Analysis of covariance was used with baseline values and weight change as covariates to examine whether the effects of enavogliflozin persisted after adjusting for weight change. Correlations between adipokine changes and key metabolic parameters were also assessed. Over the 24 weeks, the enavogliflozin group showed increased adiponectin levels with a least squares (LS) mean difference of 0.98 mg/L compared with the placebo group, while leptin levels showed a significant decrease with an LS mean difference of −2.99 µg/L. Enavogliflozin significantly reduced leptin levels over 24 weeks after adjusting for weight change; however, adiponectin changes were not significant after adjusting for weight change. Adiponectin levels significantly increased across weight loss categories, but leptin showed no significant differences. Leptin changes over 24 weeks significantly were positively correlated with changes in homeostasis model assessment of insulin resistance and homeostasis model assessment of β-cell function but significantly negatively correlated with changes in serum ketone and urinary glucose-to-creatinine ratio. Enavogliflozin treatment decreased leptin over 24 weeks in patients with type 2 diabetes, and this effect remained significant after adjusting for weight change, suggesting an improved adipokine profile. Reductions in leptin were also associated with improvements in insulin resistance and increases in serum ketone levels. These results highlight enavogliflozin as a potential treatment beyond glycemic control, offering additional benefits in managing metabolic dysregulation associated with type 2 diabetes. Not applicable (post hoc analysis).

We aimed to examine the correlation between periodontitis and body size phenotypes in 7301 participants without diagnosed chronic diseases in the Korean National Health and Nutrition Examination Survey 2013–2015. The participants were categorized into the following body size phenotype groups based on body mass index and the presence of metabolic syndrome: metabolically healthy normal weight (MHNW), metabolically abnormal normal weight (MANW), metabolically healthy obese (MHO), and metabolically abnormal obese (MAO). The prevalence rates of mild and severe periodontitis were 18.1% and 7.5%, respectively. Patients with periodontitis were older, current smokers, had a lower family income, were less likely to engage in regular tooth brushing or exercise, and had a higher body mass index and glucose levels. Periodontitis was more prevalent in the MANW and MAO groups than in the MHNW and MHO groups. Compared with the MHNW phenotype, the MAO and MANW phenotypes were significantly associated with mild and severe periodontitis, and the MHO phenotype was significantly associated with mild periodontitis. The MANW and MAO phenotypes are independent risk factors for periodontitis in adults without diagnosed chronic diseases. To enhance public health, a greater focus and effective approaches for identifying metabolic disease phenotypes among individuals with periodontal disease may be clinically relevant.