Natural AAV serotypes often lack specificity and efficiency, leading to off-target effects and a low therapeutic index. To overcome these limitations of naturally occurring serotypes, there has been a keen interest in the field to engineer novel capsids to enhance tissue and cell-specific targeting, resulting in a high number of published literature reports over the past few years. To ensure a systematic review and illustrate advances in engineered capsids that enhance specificity and efficiency, we used Natural Language Processing with Linguamatics i2E to identify neurotropic and ocular AAV capsids tested in non-human primates. By querying PubMed abstracts for specific mentions of AAVs, administration routes, and organ/tissue/species, we obtained 5907 hits, refined through an optimized process to 36 relevant and unique abstracts. Notable findings include numerous novel capsids summarized by route of administration: (1) systemic administration, targeting the central nervous system (e.g., AAV-PHP.eB, AAV X1.1, and AAV.PAL2), (2) direct central nervous system injection (e.g., AAV2.Retro, Olig001, and AAV2.1A), and (3) ocular administration (e.g., AAV.44.9 (E531D), rAAV2tYF, and Anc80L65). Such engineered capsids exhibit enhanced tissue specificity, improved pharmacokinetics and pharmacodynamics, or reduced off-target effects compared to the parent serotypes. Our study provides insight into state-of-the-art translational and drug-development considerations for engineered neurotropic and ocular capsids. We also highlight the effectiveness of Natural Language Processing and Large Language Models as tools in identifying and characterizing engineered neurotropic and ocular AAV capsids to summarize this rapidly growing class of drugs and area of therapeutics.

Proteomics can identify pharmacodynamic (PD) biomarkers by detecting protein changes in response to drug treatment, providing insights into drug mechanism and biological effects. In this study, we profiled over 7000 plasma proteins to identify potential PD biomarkers for the interleukin-5 (IL-5) inhibitors mepolizumab and reslizumab, which are approved for treating eosinophilic asthma. We used longitudinal plasma samples from healthy participants treated with a single dose of mepolizumab (n = 8, 24 mg) or reslizumab (n = 8, 0.8 mg/kg), or placebo (n = 8) to identify differentially expressed proteins. We then characterized PD biomarker candidates by their magnitude of response, area under the effect curve (AUEC), dose-response, variability, and replication of response at a lower dose for mepolizumab (n = 8, 12 mg) or reslizumab (n = 8, 0.4 mg/kg) compared to placebo. Eosinophil major basic protein (EMBP) and proteoglycan-3 (PRG3) were differentially expressed in response to mepolizumab and reslizumab, respectively, achieving Bonferroni-adjusted statistical significance (p-value < 6.86E-06) and nominal significance (p-value < 5.0E-05) with the other IL-5 inhibitor. EMBP showed a > 20% fold change difference with mepolizumab (24 mg) versus placebo at peak time, and PRG3 demonstrated a > 20% fold change with reslizumab (0.8 mg/kg) versus placebo at peak time. Both proteins had significant AUEC with both drug doses, with EMBP AUEC only significant (absolute AUEC high > low dose) at the higher mepolizumab dose. Both biomarkers showed dose-response trends and comparable variability to placebo. Our study identified EMBP and PRG3 as promising plasma PD biomarkers for IL-5 inhibitors, warranting further validation for early phase trials and biosimilar development programs.

There has been growing interest in precision dosing of beta-lactam antibiotics in recent years. At our institution, a quaternary children's hospital, we launched a new PK consult service utilizing a model-informed precision dosing (MIPD) approach to provide personalized dosing recommendations for cefepime. This consult service leveraged the infrastructure of an existing PK consult service at our institution for other drugs, such as immunosuppressants. In this manuscript, we describe the challenges in the development of a beta-lactam PK consult service due to fundamental differences between the new service and the existing PK consult service, such as varying levels of evidence for target goals for beta-lactam antibiotics versus immunosuppressants, and how they were addressed. We then present the workflow and infrastructure of our beta-lactam PK consult service to provide guidance for other institutions who may be interested in launching a similar service. Lessons learned throughout the process of building the service, including the importance of engaging multiple, diverse stakeholders early on and starting with one drug at a time, are provided.

We assessed the predictive value of MAdCAM-1 expression on response to vedolizumab in patients with inflammatory bowel disease. This was a retrospective, single-center, cohort study including 109 patients with pretreatment inflammation who completed at least three doses of vedolizumab. We described clinical and endoscopic outcomes of patients based on MAdCAM-1 expression. There was no significant difference in MAdCAM-1 expression when stratified by histology. Patients in clinical remission at 14 weeks had significantly lower median baseline MAdCAM-1 expression (37425.3 vs. 46278.9, p < 0.015). There was no difference in pretreatment MAdCAM-1 expression among patients who later achieved endoscopic or biologic response. In the posttreatment cohort, lower MAdCAM-1 expression was associated with an increased likelihood of endoscopic or biologic response (36719.5 vs. 44229.9, p < 0.038). However, posttreatment MAdCAM-1 expression did not significantly differ when stratified for clinical remission at 14 weeks. Ultimately, MAdCAM-1 immunohistochemistry has limited utility as a predictive biomarker but may provide insights into vedolizumab-associated bowel healing.

This first-in-human study investigated the safety, pharmacokinetics, and pharmacodynamics of the long-acting fibroblast growth factor 21 (FGF21) analog zalfermin. Healthy male participants (n = 56) with body mass index 25.0-34.9 kg/m were randomized to single ascending doses (2, 6, 12, 24, 48, 96, and 180 mg) of subcutaneous zalfermin or placebo. In a second study, a single dose of 12, 30, or 96 mg was administered to Japanese (n = 24) and non-Asian (n = 18) healthy males to confirm a consistent safety and pharmacokinetic profile across ethnicity. Overall, 98 participants were enrolled across both studies and followed for 36 days. Blood samples were obtained for safety and for pharmacokinetic and pharmacodynamic assessments. The primary endpoint for both studies was the number of adverse events from treatment initiation to the end of follow-up, which was greater in the highest zalfermin dose cohorts in both studies. Adverse events were non-serious, mainly gastrointestinal-related, and mostly mild to moderate in severity; no deaths occurred. In both studies, dose proportionality was established for maximum serum concentration and area under the curve from time 0 to infinity. Time to maximum serum concentration ranged from 24 to 54 h. The serum half-life of zalfermin was ~120 h in both studies, compatible with once-weekly dosing. Significant improvements in plasma lipids were observed. Zalfermin had an acceptable safety profile across all single ascending doses, consistent with the FGF21 class. Further investigations into multiple ascending doses of zalfermin and treatment duration are warranted to assess the potential treatment of steatohepatitis and cardiometabolic disease. Trial Registration: ClinicalTrials.gov (NCT03015207 and NCT04722653).

Rivaroxaban is an oral anticoagulant that requires food intake at high doses (15 and 20 mg) due to a pronounced food effect. AD-109 is a novel formulation of rivaroxaban 18 mg, designed to enhance oral bioavailability and mitigate the food effect. This study aimed to evaluate the pharmacokinetics (PKs) of AD-109 compared to the conventional formulation, Xarelto (Xarelto, rivaroxaban 20 mg) and the effect of food on the PK of AD-109. Two open-label, single-dose, two-period, two-sequence crossover studies were conducted. In Study 1, participants received a single dose of AD-109 and Xarelto under fed state, while in Study 2, participants received a single dose of AD-109 under fed and fasted state. Serial blood samples were collected up to 34 h post-dose and PK parameters were calculated by non-compartmental method. In both studies, 33 out of 36 volunteers completed the study. The geometric mean ratios (GMRs) and their 90% confidence intervals (CIs) for the maximum plasma concentration (C) and area under the curve until the last measurable concentration (AUC) of rivaroxaban for AD-109 to Xarelto were 1.0466 (0.9961-1.0996) and 0.9450 (0.9094-0.9819), falling within the bioequivalence range of 0.8-1.25. The corresponding values of AD-109 in the fed to fasted state were 1.0475 (0.9789-1.1209) and 0.9795 (0.9371-1.0238), suggesting the systemic exposure was not substantially influenced by food intake. AD-109 (rivaroxaban 18 mg) demonstrated a PK profile comparable to that of Xarelto (rivaroxaban 20 mg) and effectively minimized the food effect on drug exposure.

Chronic kidney disease is a progressive condition with limited therapeutic options in its advanced stages. Adipose-derived stem cell therapy has shown potential in preclinical studies for renal repair. This study evaluated the short-term stability of renal function in patients with moderate to severe chronic kidney disease who received adipose-derived stem cell therapy, using a matched control group derived from real-world clinical data for comparison. A total of 34 treated patients were matched in a one-to-five ratio with 170 control patients based on key clinical characteristics. The primary outcomes included the mean percentage change in estimated glomerular filtration rate and the incidence of renal function decline exceeding defined thresholds. To enhance the robustness of treatment effect estimation, real-world data were utilized to construct an external control group that closely resembled the clinical trial population. This approach allowed indirect treatment comparisons and strengthened the internal validity of findings in the absence of randomization. Results demonstrated that the treated group exhibited a more stable renal function trajectory and a significantly lower risk of deterioration compared to the control group, particularly in patients with more advanced disease. Among dose groups, the low-dose group showed the greatest stability in renal function. These findings support the feasibility of using real-world data to construct external comparators and suggest that stem cell therapy may offer a short-term stabilizing effect on renal function. Further research is needed to validate these findings and explore their long-term clinical implications. Trial Registration: ClinicalTrials.gov identifier: NCT02933827 (registered October 13, 2016. https://clinicaltrials.gov/study/NCT02933827).

To investigate if a newly developed tadalafil oral soluble film (OSF) was bioequivalent to the approved tadalafil tablets, a clinical study was conducted in healthy Chinese male volunteers under fasting conditions. In this study, 36 volunteers were randomized into three groups and received one tadalafil tablet, one tadalafil OSF with water, or one OSF without water in each period. The dosages were all 10 mg. Blood samples were collected and centrifuged. Plasma concentrations of tadalafil were determined by liquid chromatography tandem mass spectrometry. Pharmacokinetic (PK) parameters including maximum plasma concentration (C), area under the concentration versus time curve (AUC) from dosing to the last sampling time (AUC), AUC from administration to infinity (AUC), time to C, half-life and terminal elimination rate constant were calculated. Primary PK parameters including C, AUC, and AUC were logarithmically transformed and an analysis of variance was applied to determine the bioequivalence between the reference and test formulation, as well as bioequivalence between tadalafil OSF administered with or without water. Safety was assessed by adverse events (AEs), serious adverse events (SAEs) and results of laboratory tests and examinations. The 90% confidence intervals of geometric mean ratios of primary PK parameters were all within the bioequivalence range of 80.00%-125.00%. AEs were mild or moderate and no SAEs were reported. Under fasting conditions, the test OSF formulation was bioequivalent to the reference tablets, and the test OSF administered with water was bioequivalent to that without water. All investigational formulations were well tolerated in the study. Trial Registration: chinadrugtrials.org.cn (CTR20181044).

Photoreceptor transplantation is being studied to restore visual function in retinal diseases causing blindness, including age-related macular degeneration, hereditary eye diseases, and traumatic retinopathy. Preclinical studies often involve delivering exogenous human photoreceptor cells into animal models' retinas. A key readout in such experiments is distinguishing donor cell integration from artificial labeling secondary to material transfer of cytosolic or nuclear labels. Recognizing donor (human) versus animal photoreceptor nuclei is key, but purely immunohistology discrimination is challenging due to antigenic species overlap or intercellular antigen transfer. To address this, we sought to develop and validate a computational technique to discriminate between photoreceptor cells of different animal species based on machine learning of nuclear morphology. We aim to evaluate the feasibility of computer-assisted nuclear detection combined with random forest classification to automate species differentiation in DAPI-stained photoreceptors after xenotransplantation into mouse and pig retinas. Our models were trained on single-species samples and validated with mixed-species samples. We then transplanted human embryonic stem cell-derived retinal organoid cells into rodent and pig retinal degeneration models. The random forest model accurately determined cell identity post-xenotransplantation, validated by histological assessment using an antihuman nuclear antibody. Our results support the potential efficacy of employing machine learning image analysis and classification techniques that may promote experimental rigor, minimize observer bias, and enable high throughput semiautomated workflows for transplantation outcomes analysis. The methodological framework reported here may enable a more nuanced and precise analysis of the behavior of transplanted photoreceptors for the purposes of human retinal regeneration.

Artificial Intelligence (AI) is transforming drug development and regulatory submission by enabling advanced data analytics, predictive modeling and intelligent decision support systems. Beyond efficiency gains, AI establishes a translational bridge between model-informed drug development (MIDD) and clinical implementation, turning regulatory evidence into actionable insights that enhance therapeutic precision and patient outcomes. This perspective paper explores AI's current applications, regulatory integrations, and future prospects in accelerating data-driven, patient-centered drug development.

Enzalutamide and abiraterone are hormonal treatments that improve survival in metastatic castration-resistant prostate cancer. Identifying genetic variants associated with the clearance of these drugs may aid in improved dosing and outcomes. We performed genetic association studies of enzalutamide and abiraterone oral clearance in the Alliance A031201 clinical trial. Genome-wide genotyping was performed with the primary analysis limited to European-descent participants. Pharmacogene metabolic phenotypes were estimated using PyPGx and Stargazer. Associations of metabolic activity groups for CYP3A4, CYP3A5, CYP2C19 and SLCO1B1 with enzalutamide clearance (N = 706) and CYP3A4, SLCO2B1 and UGT1A4 with abiraterone clearance (N = 323) were tested by linear regression. Targeted SNP associations were assessed for abiraterone clearance at loci proximal to major metabolizing genes. Full genome-wide association studies were performed for both sets of clearance values. No significant associations were identified between metabolic phenotypes and enzalutamide or abiraterone oral clearance SNPs in the SULT2A1 5' flanking region were significantly associated with lower abiraterone clearance, (rs296373, minor allele frequency = 0.15, β = -0.457, p = 3.2E-06). Liver protein and liver and adrenal gland gene expression QTL databases indicated significantly lower SULT2A1 expression patterns for individuals carrying associated alleles, likely explaining the lower abiraterone oral clearance. CYP2C8*3 was associated with higher enzalutamide clearance (p = 0.012), but this was not significant after correction for multiple testing. This study is the first to identify the genetic association of SULT2A1, known to be involved in the metabolism of steroids in the liver and adrenal glands, with abiraterone clearance. Genetic variation in SULT2A1 may be useful to inform personalized dosing of abiraterone. ClinicalTrials.gov Identifier: NCT01949337.

Cell and gene therapies (CGTs) are transforming medicine by offering potential cures for diseases previously considered untreatable. Despite rapid advancements, challenges remain in optimizing efficacy and safety and ensuring patient accessibility and preference due to high costs and clinical uncertainties, particularly for rare diseases and one-time administration. The American Society of Clinical Pharmacology & Therapeutics (ASCPT) held a CGT satellite conference in 2025, titled "Cell and Gene Therapy: Transforming Treatment Paradigms for Patient-Centric Care." This manuscript summarizes the conference, covering gene therapies and T-cell immunotherapies from scientific, clinical, and patient-centered perspectives. Key topics on gene therapy included "platformization" to streamline development, lessons from adeno-associated virus-based gene therapies for hemophilia from patient and clinical perspectives, clinical pharmacology, and model-informed drug development (MIDD) considerations. The conference also highlighted T-cell immunotherapies including chimeric antigen receptor T therapy (CAR T), focusing on factors affecting cellular kinetics, efficacy, and safety, as well as emerging allogeneic CAR T for autoimmune diseases and MIDD strategies to optimize therapy design and clinical outcomes.

Pharmacogenomic (PGx) testing using multi-gene panels (mgPGx) is documented to improve clinical outcomes; however, real-world data on its economic impact remain limited. This study aimed to evaluate the utility and economic value of mgPGx testing among Medicare patients within a community-based health system. We identified Medicare Advantage patients within the primary care setting of a community-based health system hospital who were taking ≥ 1 PGx-guided medication using a stratification algorithm. In total, 1042 patients participated in mgPGx testing. We evaluated the prevalence of PGx medications, polypharmacy involving PGx medications, and actionable results (i.e., a phenotype with PGx guidance and a relevant PGx medication). A Total Cost of Care (TCOC) analysis was performed for a subset of patients (n = 548) who underwent PGx testing and were matched to a control group that did not undergo PGx testing using propensity score matching. Total medical expenses over 12 months, both before and after testing, were compared. Forty-four percent (n = 454/1042) of patients were ≥ 3 PGx-guided medications. Over one-third of patients who were on ≥ 3 PGx medications had ≥ 2 actionable results (35.5%, n = 161/454). The TCOC analysis demonstrated a trend toward a net cost savings of $1827 per member per year (PMPY), with $1582 in medical savings and $245 in pharmacy savings. Polypharmacy with PGx medications is prevalent, and mgPGx led to cost savings. Further research with a larger sample size is needed to replicate the results and assess the long-term impact on healthcare utilization and costs.

Prognostic assessment of chronic thromboembolic pulmonary hypertension (CTEPH) remains challenging. Stress hyperglycemia, a condition where glucose metabolism is regulated during stress, has been regarded as an indicator of acute hyperglycemia. The stress hyperglycemia ratio (SHR) serves as a more precise marker for this state. This research intended to investigate the prognostic function of SHR in CTEPH, as its link to poor outcomes is uncertain. Clinical deterioration events were the primary endpoint. LASSO regression was utilized for variable selection and dimensionality reduction to identify key features and mitigate overfitting. Kaplan-Meier analysis, multivariable Cox regression, and restricted cubic splines were primarily used to investigate the link between SHR and adverse clinical outcomes. Internal validation was performed using bootstrap resampling. Sensitivity analysis was performed to assess the robustness of the findings. The study included a sum of 451 patients with CTEPH; over a median follow-up of 21 months, 89 (19.7%) patients encountered adverse outcomes. Kaplan-Meier analysis indicated that patients having elevated SHR levels exhibited a markedly higher overall incidence of adverse events. Restricted cubic spline analysis showed a linear relationship between SHR and adverse events. Multivariable Cox regression analysis indicated that higher SHR independently predicts adverse outcomes, whether treated as continuous (hazard ratio, 1.541; 95% confidence interval, 1.252-1.896, p < 0.001) or categorical (hazard ratio, 2.419; 95% confidence interval, 1.268-4.616, p = 0.007). Internal validation demonstrated that the original C-index was 0.693, with a bias-corrected C-index of 0.675 after bootstrap validation. In patients with CTEPH, higher SHR is independently associated with clinical worsening. The prognostic significance of SHR remained robust across internal validation and multiple sensitivity analyses.

Janus kinase inhibitors (JAKIs) are immunomodulatory drugs used for autoimmune and inflammatory conditions. Their potential impact on pregnancy and fetal development remains a concern due to placental transfer and potential disruption of cytokine and growth factor signaling, with limited human data. This study analyzed VigiBase, the World Health Organization global pharmacovigilance database of individual case safety reports (ICSRs), to assess signals of disproportionate reporting (SDRs) for pregnancy-related adverse drug reactions (ADRs) reported with systemic JAKIs, including abrocitinib, baricitinib, deucravacitinib, fedratinib, filgotinib, itacitinib, momelotinib, pacritinib, peficitinib, ritlecitinib, ruxolitinib, tofacitinib, and upadacitinib. As of May 26, 2024, 163 ICSRs met inclusion criteria, mainly from North America (41.7%) and Europe (39.3%). The most frequently reported JAKIs were tofacitinib (44.8%) and upadacitinib (34.4%), primarily indicated for rheumatoid arthritis (29.4%). Among 213 pregnancy-related ADRs, spontaneous abortion was the most frequently reported event (47.9%) without representing an SDR compared with other drugs in the database (reporting odds ratio [ROR] 0.37, 95% confidence interval [CI] 0.30-0.46). Congenital anomalies were reported in 16.0% of ICSRs (43 events), but no specific organ-related patterns were identified. Prematurity occurred in 9.2% of ICSRs, without SDR compared to the full database (ROR 0.07, 95% CI 0.04-0.11). Current pharmacovigilance data from VigiBase do not indicate SDRs for spontaneous abortion or prematurity following JAKI exposure during pregnancy. Findings should be interpreted cautiously given the limitations of spontaneous reporting systems and the exploratory nature of the analysis. Further studies are needed to better characterize the JAKI safety in pregnancy.

N,N-dimethylacetamide (DMA) is an organic solvent, used in busulphan, iv-formulation, (Busulfex). DMA is metabolized primarily to N-methylacetamide (MMA) via CYP2E1. In the present study, we investigated the pharmacokinetics and toxicity of DMA and MMA in patients, mice and cell lines. In pediatric patients (6 months to 18 years) undergoing hematopoietic stem cell transplantation, the pharmacokinetics of DMA and MMA were followed during the 4-days Busulfex conditioning (3.2-4 mg/kg, b.i.d). No accumulation of DMA was found; however, a significant increase in clearance and a significant decrease (p < 0.005) in half-lives by the end of treatment were observed which might indicate CYP2E1 autoinduction. Furthermore, continuous increases in plasma concentration of MMA were observed during treatment and a terminal half-life of 15.2 ± 1.7 h was detected. Moreover, ALT was significantly (p = 0.04) increased in > 61% of the patients after conditioning. Additionally, mice were treated with either dimethyl sulfoxide (DMSO), DMA, busulphan in DMSO, Busulfex or saline for 4 days. DMA-treated mice showed elevated ALT and AST values. Interestingly, Busulfex administration did not alter mice liver enzymes. Busulphan in DMA showed higher cytotoxicity compared to busulphan in DMSO in HepG-2, Huh-7 and HL-60 cells. The combination Bu-DMA-MMA exhibited increased cytotoxicity in a concentration-dependent manner. In conclusion, Busulfex administration to pediatric patients resulted in an accumulation of MMA during the 4-days treatment. Busulfex is less toxic compared to Bu dissolved in DMA. MMA addition to Bu in DMA showed higher cytotoxicity. Therefore, MMA with a relatively long half-life may induce hepatotoxicity and/or interaction with subsequently administered drugs; thus further investigations are urgently warranted.

The onset of the global COVID-19 pandemic created an urgent need for therapeutic monoclonal antibody (mAb) development, while the rapid mutation of the SARS-CoV-2 virus and emergence of new variants presented a moving target for validation of efficacy. Since it is virtually impossible to conduct randomized controlled trials in the context of a continually evolving variant landscape, other sources of data can inform ongoing effectiveness and appropriate dosing of existing treatments against new variants. This may include data from in vitro neutralization testing, real-world studies, and clinical pharmacology studies. There are various clinical pharmacology approaches available to aid in dose selection of COVID-19 mAbs, and the approach used for initial dose selection may differ from that used to justify dose modifications in light of new variants. At present, there is no universally accepted approach that has been shown to work in all circumstances, and most of the available methods lack validation against clinical data. Here, we provide an overview of the different pharmacological approaches available for mAb dose selection or dose adjustments, outlining advantages and limitations of each as well as assumptions, data requirements, and key learnings for each method based on experiences with COVID-19 mAb development over the last 4 years. Future mAb development programs for COVID-19 or other viral infections with pandemic potential should take into consideration lessons learned from the COVID-19 pandemic and devise clinical development programs that generate data to help address new emerging variants of concern in a rapidly evolving virus landscape.

Breast cancer is among the most common cancers in U.S. women. Epidermal growth factor receptor inhibitors (EGFRIs) target pathways driving tumor growth but frequently cause dermatologic toxicities that impact quality of life and treatment adherence. This review summarizes the clinical features, mechanisms, and management of EGFRI-related skin adverse effects. A comprehensive PubMed search yielded 134 studies that discussed EGFRI treatment in breast cancer patients. Studies were included if they published over the past 10 years (between 2014 and 2024), reported data on females treated with EGFRI for active breast cancer, and included cutaneous side effects. Ninety articles met this inclusion criteria. Findings indicate that the severity of skin toxicity is influenced by patient-specific factors such as age, nutrition, lifestyle, genetics and ethnicity, as well as treatment-related factors including drug dosage and combination therapies. Common toxicities include papulopustular rashes, xerosis, pruritus, alopecia, and severe reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis. The specific type of EGFRI (monoclonal antibodies or tyrosine kinase inhibitors) also affects the nature of dermatological reactions. Management strategies include prophylactic skin care, symptomatic treatments, and emerging therapies such as laser therapy. Chemotherapy-induced skin toxicities from EGFRI in breast cancer treatment significantly impact patient quality of life and treatment adherence. This study underscores the need for proactive management as well as conversations with patients regarding the cutaneous adverse effects prior to starting EGFR treatment to enhance patient awareness.

Malnutrition implies a decline in the systemic status and organ function, which is closely related to sarcopenia, frailty, osteoporosis, and prognosis. Diabetes medications work in a multifaceted manner on various tissues, such as the pancreas, muscle, liver, and adipose tissue; these medications affect metabolism, which in turn affects nutritional status. This study aimed to determine the effect of diabetes medications on the scores of the Geriatric Nutrition Risk Index (GNRI) and Controlling Nutritional Status (CONUT) nutritional indices, both cross-sectionally and longitudinally. This cross-sectional study included 2146 individuals who were prescribed diabetes medications. Multivariate analysis showed that both GNRI and CONUT scores tended to be improved in patients using sodium-glucose cotransporter 2 inhibitors (SGLT2i), dipeptidyl peptidase 4 inhibitors (DPP4i), or biguanide (BG). Additionally, propensity score matching of nutrition-related laboratory values was performed to assess the variation in nutritional indices over time, which resulted in less deterioration of the GNRI in the SGLT2i and BG groups. In conclusion, this study suggests that SGLT2i and BG prevent the progression of malnutrition and may help in selecting drugs that consider the nutritional status of patients.