remogliflozin etabonate + vildagliptin (Remozen V / Remo V)

Longitudinal Changes in Corneal Epithelial and Central Corneal Thickness in Type 2 Diabetes Assessed by AS-OCT: A Real-World Study.

Boyacı İhsan İ, Demirci Göktuğ G

To evaluate longitudinal changes in central corneal epithelial thickness (CCET) and central corneal thickness (CCT) using anterior segment optical coherence tomography (AS-OCT) over 12 months in adults with type 2 diabetes receiving one of two routinely prescribed oral antidiabetic regimens, and to explore their association with glycemic changes. In this retrospective observational cohort study, 40 adults with type 2 diabetes receiving one of two routinely prescribed treatment regimens (vildagliptin-metformin, n=19; empagliflozin-metformin, n=21) underwent AS-OCT at baseline, 3 months, and 12 months. Glycated hemoglobin and fasting plasma glucose were assessed at each visit. Precision analysis indicated detectable between-group differences of 4.7 µm for CCT and 6.1 µm for CCET. Both groups showed significant within-group glycated hemoglobin improvement (mean reduction: -2.28% and -2.88% in the vildagliptin-metformin and empagliflozin-metformin groups, respectively; p<0.05) without between-group differences. CCT and CCET showed no statistically detectable longitudinal change over 12 months, with no significant differences in longitudinal change between groups. Glycated hemoglobin change showed a modest independent association with CCT change (β = 0.81 µm per 1% glycated hemoglobin; 95% CI 0.20-1.42; p=0.011; n=32). Corneal structural parameters showed no statistically detectable longitudinal change or between-group difference over 12 months. Given the modest sample size and observational design, these findings should be considered hypothesis-generating and require confirmation in larger prospective studies.

In Silico Identification of Novel Leads as Potential DPP-IV Inhibitors as Antidiabetic Agents Using Virtual Screening.

Turkar Milendra Kumar MK, Ahirwar Rahul R, Sahu Rishika R, Bhadane Rajendra R et al.

Purpose: Dipeptidyl peptidase-IV (DPP-IV) is a validated therapeutic target for type 2 diabetes mellitus due to its role in incretin hormone degradation. This study aimed to identify novel small-molecule DPP-IV inhibitors from the ECBD database using an integrated virtual screening and molecular dynamics (MD) approach, acknowledging that experimental validation is necessary to confirm biological activity. Methods: Structure-based virtual screening of 5,500 ECBD compounds was performed using molecular docking to identify high-affinity ligands, followed by interaction analysis with key catalytic residues. Pharmacokinetic suitability was evaluated through in-silico ADMETox profiling. The top-ranked hits were further subjected to 100 ns MD simulations to assess complex stability and conformational effects on the DPP-IV active site. Binding free energies were calculated using the MM/GBSA method, and docking reliability was validated through redocking experiments. Results and Discussion: Five compounds EOS34295, EOS4915, EOS9480, EOS2567, and EOS62725 exhibited stronger noncovalent binding affinities than vildagliptin and formed stable interactions with essential residues, including GLU205, GLU206, ASN710, and PHE357. ADMETox predictions indicated favorable oral drug-likeness. MD simulations revealed stable protein-ligand complexes, with lower RMSD values for the hit ligands (1.20-1.51 Å) compared with vildagliptin (1.90 Å). RMSF analysis showed consistent flexibility without destabilizing fluctuations. Additional hydrogen-bond interactions with PHE357 emerged during MD simulations, indicating enhanced binding persistence. MM/GBSA analysis confirmed stronger binding energies for EOS34295 (-56.58 kcal/mol), EOS62725 (-37.90 kcal/mol), and EOS2567 (-31.27 kcal/mol) relative to vildagliptin (-23.88 kcal/mol). Conclusion: This study identifies EOS34295, EOS2567, and EOS62725 emerged as promising DPP-IV inhibitory hits with superior binding stability, supporting their potential as antidiabetic leads for future experimental validation.

Vildagliptin-Induced Leukocytoclastic Vasculitis: A Case Report and Review of Published Cases.

Zouaoui Nour Elhouda NE, Hamza Imen I, Charfi Ons O, Debbeche Sana S et al.

Remogliflozin attenuates thioacetamide-induced nephrotoxicity: association with Nrf2/HO-1, SIRT1/AMPK, and TLR4/NF-κB pathway modulation.

Qadri Marwa M, Almarghalani Daniyah A DA, Alarifi Abdulaziz A, Mohamed Bassim M S A BMSA et al.

Thioacetamide (TAA) induces renal injury via oxidative stress and inflammation. Remogliflozin (Remo), an SGLT2 inhibitor, was evaluated for potential renoprotection. Twenty-four male Wistar rats were assigned to control, TAA (100 mg/kg IP twice weekly), TAA + Remo 25 mg/kg, or TAA + Remo 50 mg/kg (oral daily). Outcomes included renal function, oxidative stress (GSH, SOD, MDA), antioxidant biomarkers (Nrf2, HO-1), inflammatory mediators (TLR4/NF-κB, TNF-α, IL-1β), metabolic/kinase biomarkers (SIRT1, AMPK, PI3K, AKT), and histopathology/immunohistochemistry (mTOR, MYD88, Nrf2). Remogliflozin was associated with lower serum creatinine, urea, and uric acid, with endpoint-specific differences between doses. Remo was associated with higher renal Nrf2, HO-1, SIRT1, and p-AMPK, and lower MDA, TLR4, NF-κB, TNF-α, IL-1β, PI3K, and AKT. Histopathology and IHC showed associations with reduced tissue injury, lower mTOR and MYD88 immunoreactivity, and increased Nrf2 staining. While the 50 mg/kg group showed changes in more markers, this does not establish uniform dose superiority or a formal dose-response relationship; at 25 mg/kg, effects differed among AMPK-related endpoints. Direct 25-versus-50 mg/kg comparisons were included in the Tukey-Kramer analysis for each endpoint. No pharmacokinetic measurements or formal dose-response analyses were performed. In this exploratory model, remogliflozin was associated with attenuation of TAA-induced renal injury and modulation of related biomarkers. Causal mechanisms remain to be confirmed by targeted intervention studies. Findings are limited to young male Wistar rats and should not be generalized to other populations or clinical settings. Remogliflozin warrants further preclinical investigation in TAA-associated renal injury.