Introduction: Metformin is the first-line oral therapy for type 2 diabetes mellitus (T2DM), but its pharmacokinetics and therapeutic response show high interindividual variability. Genetic polymorphisms in organic cation transporters (OCTs) significantly influence metformin's absorption, distribution, and elimination. OCT1 (SLC22A1), OCT2 (SLC22A2), and OCT3 (SLC22A3) mediate metformin transport across enterocytes and renal epithelial cells. Understanding these polymorphisms is crucial for optimizing therapy and advancing precision medicine.

Aim: To investigate the prevalence of OCT1, OCT2, and OCT3 genetic polymorphisms and evaluate their effect on the pharmacokinetics of metformin using a pharmacometrics approach.

Methods: The study was conducted in three phases. First, genotyping was performed to determine allele and genotype frequencies of select OCT variants. Second, plasma metformin concentrations were quantified using LC-MS/MS. Finally, a pharmacokinetic analysis was conducted using Non-Compartmental Analysis (NCA) and population pharmacokinetic (PopPK) modeling with FOCEI in PUMAS® v.1.40.1. Unpaired t-tests compared pharmacokinetic parameters between wild-type and mutant genotypes. Covariates were incorporated to explain interindividual variability.

Results: Among 230 samples, rs628031 (OCT1) showed 10% homozygous wild, 41% heterozygous, and 48.7% homozygous mutant genotypes. rs622342 (OCT1) had 22.6% wild, 53.7% heterozygous, and 23.5% mutant; rs316019 (OCT2) had 10.9% wild, 38.6% heterozygous, and 50.4% mutant; rs2076828 (OCT3) had 63.8% wild, 22.7% heterozygous, and 13.4% mutant. Metformin clearance was estimated at 97.4 L/hr and volume of distribution at 186.8 L. Incorporation of OCT2 genotype as a covariate reduced clearance variability from 55.7% to 20.2%, indicating significant influence on drug elimination.

Conclusions: OCT2 polymorphisms are significantly associated with reduced metformin clearance and volume of distribution, unlike OCT1 variants. These findings support the clinical relevance of OCT genotyping for individualized metformin therapy and warrant further validation through therapeutic drug monitoring.

Keywords: Genetic Polymorphism, Organic cation transporter, Metformin

Introduction: Paediatric ICUs have a high DRP risk due to polypharmacy, age-related pharmacokinetics and complex regimens in critically ill children.
Aims: The study aimed to evaluate the impact of clinical pharmacist (CP) interventions on DRPs, clinical & cost outcomes for provision of pharmaceutical care services in critically ill patients.
Methods: A prospective interventional study was conducted in the PICU in two phases—pre-intervention and post-intervention. Outcomes were assessed by using odds ratio & cost benefit analysis.
Results: A total of 449 pediatric patients were included (n=231, pre-phase; n=218, post-phase). DRP occurrence significantly reduced from 0.66 to 0.49 per patient (p=0.007). The average PICU stay was decreased from 3.90 to 2.81 days (p=0.001), and the number of drugs prescribed reduced from 9.01 to 7.06 (p=0.000). DRPs pertaining to treatment efficacy (74.93%) and safety (15.91%) were most common prevalent. Clinical pharmacist interventions led to complete resolution of 70% of identified DRPs, with 91% intervention acceptance rate and 65% fully implemented. Economically, pharmacist-led interventions result in a cost savings of INR 8,675 and cost avoidance of INR 31,813.54. After deducting service costs (INR 33,333), the net benefit was INR 7,155.54. The benefit-cost ratio was 1.24, with INR 268.13 saved per intervention and INR 185.72 per patient, reflecting cost-neutral but clinically impactful service.
Conclusion: Clinical pharmacist interventions in the PICU significantly enhanced medication safety, reduced DRP rates, shortened ICU stays, and cost benefit. Integrating pharmacists as ca key member of ICU care teams improves therapeutic outcomes and enhanced pediatric critical care delivery.
Key words: Clinical pharmacist, drug related problems, cost benefit analysis.

Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with increased risks of brain-related diseases such as dementia, Parkinson’s disease, and ischemic stroke. Sodium-glucose cotransporter-2 inhibitors (SGLT2Is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) have shown protective effects against these conditions, but evidence in patients with MASLD remains limited.
Aims: To compare the effects of SGLT2Is and GLP-1RAs with dipeptidyl peptidase-4 inhibitors (DPP-4Is) on the risk of brain-related outcomes in patients with MASLD.
Methods: We conducted an active-comparator new-user cohort study using the Korean healthcare database (2012-2023) among patients with MASLD, identified using a validated definition. The outcomes of interest were incident Parkinson’s disease, dementia, and ischemic stroke. Two cohorts were established: one comparing SGLT2Is with DPP-4Is, and another comparing GLP-1RAs with DPP-4Is. Patients were followed from drug initiation until the earliest of outcome occurrence, death, or 31 December 2023. 1:1 propensity score matching was applied to balance covariates, and hazard ratios (HRs) with 95% confidence interval (CI) were estimated using Cox proportional hazard models.
Results: A total of 125,903 and 3,641 patient pairs were included in the SGLT2Is (mean age 52; male 72.1%) and GLP-1RAs (mean age 49; male 61.3%) cohorts, respectively, following propensity score matching. Compared with DPP-4Is, SGLT2Is were associated with lower risks of dementia (HR 0.69, 95% CI 0.64–0.74) and ischemic stroke (0.92, 0.85–0.99), with a non-significant trend for Parkinson’s disease (0.83, 0.68–1.01). Similarly, GLP-1RAs were linked to a reduced risk of dementia (0.64, 0.43–0.96), but not with Parkinson’s disease (0.98, 0.37–2.60) or ischemic stroke (1.05, 0.67–1.67).
Conclusion: In patients with MASLD, SGLT2Is may provide broad protection against neurodegenerative and cerebrovascular outcomes, while GLP-1RAs appear to confer outcome-specific benefits, particularly against dementia. Further studies are needed to confirm the robustness and generalizability of our findings.
Keywords: Antidiabetic medications; MASLD; Brain-related diseases.

Introduction: Nephrolithiasis is a multifactorial disease with many contributing factors varying across races, ethnicities, and sociocultural backgrounds. Diabetes is a significant independent risk factor for nephrolithiasis potentially leading to more severe complications.
Aims: We aimed to investigate the association between sodium-glucose co-transporter-2 inhibitors (SGLT2is) and the risk of nephrolithiasis in Thai patients with type 2 diabetes (T2D).
Methods: This retrospective cohort study of T2D patients used real-world data from Ramathibodi Hospital, Bangkok, Thailand. Adult T2D patients who received SGLT2is, sulfonylureas, thiazolidinediones, dipeptidyl peptidase 4 inhibitors, or glucagon-like peptide-1 receptor agonists were included. Patients who developed nephrolithiasis before or within one month of initial antihyperglycemic medication prescription were excluded. Inverse probability weighting with regression adjustment and Cox proportional hazards models were applied to estimate the effect of SGLT2is on the risk of nephrolithiasis.
Results: A total of 24,679 patients were identified between January 2015 - December 2023, of whom 5,754 received an SGLT2i. The median follow-up time was 2.2 years. Thirteen covariates associated with SGLT2i assignment (i.e., age, sex, diabetes duration, body mass index, HbA1c, eGFR, dyslipidemia, cardiovascular diseases, peripheral vascular diseases, diabetic retinopathy, renin-angiotensin system inhibitors, number of other antihyperglycemic drugs currently used, and healthcare coverage scheme) were selected for propensity score calculation. The incidence rate of nephrolithiasis was 8.4 per 1000 person-years in the SGLT2i group and 17.5 per 1000 person-years in the non-SGLT2i group. The risk of nephrolithiasis was significantly lower in patients who received an SGLT2i compared to those who did not, with a HR = 0.51; 95% CI: 0.39, 0.67.
Conclusions: Our real-world study suggested a lower risk of nephrolithiasis in Thai patients with T2D who were prescribed SGLT2is. These real-world findings provide an additional benefit related to prescribing SGLT2is in T2D patients to prevent nephrolithiasis.
Keywords: nephrolithiasis, sodium-glucose co-transporter-2 inhibitors, type 2 diabetes

Introduction:
Sodium–glucose cotransporter-2 (SGLT2) inhibitors are increasingly recommended as first-line treatment for type 2 diabetes mellitus (T2DM), but head-to-head data comparing them with metformin, the canonical biguanide, remain sparse in Japan.
Aims:
To compare the long-term effectiveness and cost of initiating treatment with a biguanide versus an SGLT2 inhibitor, excluding the alternative class for 12 months but permitting other antidiabetic drugs, on a composite of major cardio-cerebrovascular events and all-cause death, and a composite of diabetic complications.
Methods:
We emulated a new-user cohort trial using the Shizuoka Kokuho Database (2012–2021). Patients initiating treatment with either a biguanide or an SGLT2 inhibitor, while avoiding the alternative class during the first 12 months but allowing other glucose-lowering agents, were included. Follow-up began at treatment initiation; those who received the comparator drug within 12 months were excluded. After 1:1 propensity-score matching on demographic, clinical, laboratory, and lifestyle variables, cause-specific Cox models estimated hazard ratios (HRs). Daily medication costs were compared.
Results:
After matching, 1,246 patients (623 per group) were followed for a median of 4.0 years (maximum 8.5). Cardio-cerebrovascular composite: 44/623 biguanide users (7.1%) and 35/623 SGLT2-inhibitor users (5.6%) experienced a first event (HR 0.80, 95% CI 0.51–1.24). Diabetic complications: 86/623 (13.8%) vs. 78/623 (12.5%) (HR 0.88, 95% CI 0.70–1.13). Median daily drug cost was 124.7 JPY for biguanides and 184.0 JPY for SGLT2 inhibitors (P < 0.001).
Conclusions:
Using a large-scale regional database from Japan, we found that among adults with type 2 diabetes without prior major cardiac or renal disease, first-line treatment with an SGLT2 inhibitor did not reduce risks of cardio-cerebrovascular events, mortality, or complications compared with metformin, and cost about 50% more.

The prevalence of US childhood obesity rose from 13.9% in 2000 to 19.7% in 2024, resulting in increased risks of severe comorbidities in adulthood. The 2024 randomized clinical trial (‘SCALE Kids’) demonstrated once-daily liraglutide injection (a GLP-1) efficaciously reduced BMI compared to placebo among children aged 6-11 years.

We aim to estimate the population-level effect of liraglutide use among children 6-11 years at the ≥95th percentile of age- and sex-specific obesity. We hypothesized greater uptake of liraglutide would result in greater BMI reduction and reduced effectiveness of liraglutide would result in lower BMI reduction.

We developed a population-level estimation model that varied the assumption of uptake and the effectiveness of liraglutide, after accounting for demographic, medical, and behavioral characteristics using R version 4.5.1. We utilized nationally-representative data from the 2021-2023 US National Health and Nutrition Examination Survey (NHANES) to estimate the age- and sex-specific prevalence of obesity among 6-11 year olds. We applied similar exclusion criteria to the trial: diabetes, suicidal ideation, and secondary causes of obesity.

The model estimated an overall 0.6% decrease in BMI (95% confidence interval [CI]: -1.8% to 0.6%) at 30% uptake and an overall 1.3% decrease in BMI (95% CI: -2.4% to -0.3%) at 40% uptake. Conversely, as the effectiveness of liraglutide diminished, we observed smaller reductions in BMI. The model estimated an overall 1.4% decrease in BMI (95% CI: -2.4% to -0.5%) when liraglutide effectiveness is reduced by 6% and an overall 0.8% decrease in BMI (95% CI: -1.8% to 0.2%) when liraglutide effectiveness is reduced by 4.3%.

In conclusion, a substantial number of obese children could benefit from the widespread uptake of liraglutide if its effectiveness in the real world is similar to its efficacy observed in the SCALE Kids trial. Liraglutide use among obese children could result in a population health benefit.

Introduction: Diabetes Mellitus (DM) is a chronic condition requiring long-term care, making self-management challenging. Medication Therapy Management (MTM) is a patient-centered approach provided by pharmacists. Although assessment of the MTM practices by pharmacists (their attitudes, interests, and challenges) is needed, the lack of validated instruments hinders evaluation of pharmacists’ roles.

Aims: To develop, validate, and assess the reliability of a questionnaire evaluating community pharmacists’ practices, attitudes, and interest in MTM provision for type 2 DM in Karnataka, India.

Methods: A 20-item questionnaire was developed based on literature and expert input. Content validity was evaluated by eight experts (an endocrinologist, two community medicine specialists, a public health specialist, a community health nurse, a statistician, an academic pharmacist, and a pharmacoepidemiologist) for relevance and accuracy of the questionnaire. Item- and scale-level content validity indices (I-CVI and S-CVI) were calculated. The user testing method was employed to measure internal consistency (N=44) using Cronbach’s alpha, and test-retest reliability (N=26) was assessed using intraclass correlation coefficients (ICC) at two time points with SPSS version 28.0.

Results: All 20 items had I-CVI values above 0.87, and the S-CVI was 0.98, indicating strong content validity. Internal consistency was acceptable across all domains: interest (Cronbach’s alpha = 0.797), practice (0.811), and attitude (0.713). The overall Cronbach’s alpha for the tool was 0.871. Test-retest reliability showed good consistency over time: interest (ICC = 0.821, 95% CI: 0.696–0.908), practice (ICC = 0.849, 95% CI: 0.750–0.921), and attitude (ICC = 0.833, 95% CI: 0.722–0.913). The overall ICC for the questionnaire was 0.708 (95% CI: 0.511–0.839, p < 0.001).
Conclusions: The questionnaire demonstrated strong validity and reliability. In the future, this tool can be used to identify training needs among pharmacists and to evaluate improvements following MTM-focused training, supporting capacity-building and quality improvement in diabetes care.

Keywords: Pharmacoepidemiology, Pharmaceutical care, Questionnaire, Diabetes.