Introduction: Dipeptidyl peptidase-4 inhibitors (DPP-4i) are widely prescribed for type 2 diabetes mellitus, yet their safety profile regarding cellular immunity remains controversial. Theoretically, inhibiting the DPP-4 enzyme (CD26) on T lymphocytes could compromise T-cell activation, which might increase the risk of herpes zoster (HZ) recurrence. However, some laboratory safety data demonstrate conventional gliptins preserve T-cell proliferation and do not adversely impact cell-mediated immune responses.

Aim: This study aimed to evaluate the risk of HZ in patients with type 2 diabetes initiating DPP-4i compared to those initiating SGLT2i.

Methods: We used TriNetX U.S. Network (2016-2025) to conduct a retrospective cohort analysis under target trial emulation framework. Adults aged ≥ 18 years with type 2 diabetes were included. The index date was defined as the date of the first DPP-4i or SGLT2i prescription. Patients with prior exposure to either class within 1 year before the index date were excluded. This 1-year pre-index period also defined covariate assessment, with groups balanced via propensity score matching. The primary outcome was 5-year HZ incidence. The follow-up period extended from index date to HZ occurrence, death, attrition, or study end. Subgroup analyses were conducted based on age, sex, baseline corticosteroid use, and HbA1c level. Cox proportional hazards models and Kaplan-Meier curves estimated hazard ratios and 95% confidence intervals.

Results: Among 136,751 propensity score-matched pairs, DPP-4i initiation was not associated with significantly higher risk of HZ compared to SGLT2i (HR = 1.044; 95% CI, 0.980–1.113). Generally, results were consistent across most subgroups. However, there was a slightly elevated risk of HZ among female DPP-4i initiators (HR = 1.097; 95% CI, 1.007–1.194).

Conclusions: DPP-4i therapy is generally not associated with an increased risk of HZ compared to SGLT2i, while the potential risk observed in female patients warrants closer clinical monitoring.

Key words: DPP-4inhibitors, Herpes zoster, Type 2 diabetes

Introduction:
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) such as semaglutide and tirzepatide are used to treat type 2 diabetes and obesity. Recent case reports have linked these medications with myopathy and rhabdomyolysis.

Aims:
To systematically review case reports linking semaglutide or tirzepatide with myopathy/rhabdomyolysis and investigate associated reporting in the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS).

Methods:
We systematically searched PubMed and Embase for reports of semaglutide- or tirzepatide-associated myopathy/rhabdomyolysis and inferred the Naranjo score. FAERS reports from 2018-2025 were analysed to estimate reporting odds ratios (RORs) for semaglutide- and tirzepatide -associated myopathy/rhabdomyolysis using three comparator frameworks: other GLP-1RAs; active comparators (other GLP-1RAs, SGLT2 inhibitors, and DPP-4 inhibitors); and all other medications. Interaction with statin was assessed using additive and multiplicative interaction models and Ω shrinkage.

Results:
The systematic review identified 13 semaglutide- or tirzepatide-associated myopathy/rhabdomyolysis case reports, 12 involving weight-loss use and six had a probable association by the Naranjo scale. In FAERS, 1,378 semaglutide-associated and 916 tirzepatide-associated myopathy reports were identified, including 103 and 41 rhabdomyolysis reports, respectively. Compared with other GLP-1RAs, semaglutide showed higher reporting odds of myopathy (ROR 1.80, 95%CI 1.67-1.95) and rhabdomyolysis (1.89, 1.41-2.52), whereas tirzepatide showed lower reporting odds. Neither medication showed higher reporting odds when compared with active comparators or all other medications. Statin co-use occurred in 449 semaglutide and 126 tirzepatide myopathy cases, and 47 and 20 rhabdomyolysis cases, respectively. Tirzepatide showed weak statin interaction signal for myopathy and rhabdomyolysis in Ω shrinkage (Ω025=0.57; 0.50) and multiplicative models (ROR 1.31, 95%CI 1.08-1.60; 2.79, 1.52-5.11). Semaglutide only showed weak interaction in Ω shrinkage analyses for myopathy and rhabdomyolysis (Ω025=1.06; 0.70).

Conclusion:
Although case reports suggest myopathy and rhabdomyolysis, inconsistent signals across comparison groups were noted. Prospective studies are needed to clarify this association.

Keywords: GLP-1 receptor agonists, Disproportionality Analysis, Rhabdomyolysis

Introduction: Type 2 diabetes mellitus (T2DM) patients have twice the self-harm risk compared to the general population.The association between sodium-glucose cotransporter 2 inhibitors (SGLT-2i) and self-harm is unclear.

Aims: This study aimed to assess whether SGLT-2i use is associated with a lower risk of self-harm in T2DM patients.

Methods: Through the Shenzhen Public Health Data Platform, we constructed two cohorts (SGLT-2i versus dipeptidyl peptidase-4 inhibitors [DPP-4i], SGLT-2i versus glucagon-like peptide-1 receptor agonists [GLP-1RA]) via a target trial emulation framework with an active comparator, new-user design. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using overlapping weighting Cox regression models.

Results: The SGLT-2i versus DPP-4i cohort included 85,789 SGLT-2i users and 53,810 DPP-4i users. After a median follow-up of 1.85 years (interquartile range: 0.91-2.70), 567 (0.66%) cases of self-harm occurred in the SGLT-2i group and 567 (1.05%) in the DPP-4i group. After overlapping weighting, SGLT-2i was associated with a lower risk of self-harm compared with DPP-4i (HR: 0.86, 95%CI: 0.76-0.98), and this result was consistent across various sensitivity analyses. In the SGLT-2i (n=130,330) versus GLP-1RA (n=5,126) cohort, a lower risk of self-harm (HR: 0.76, 95% CI: 0.59-0.99) was associated with SGLT-2i compared with GLP-1RA. However, in some sensitivity analyses, no statistically significant difference was observed between SGLT-2i and GLP-1RA users.

Conclusions: SGLT-2i use is associated with a lower risk of self-harm in T2DM patients. These findings provide supportive evidence for the safety of SGLT-2i and highlight their potential role in mental health management of T2DM patients.

Keywords: type 2 diabetes mellitus, self-harm, sodium-glucose cotransporter-2 inhibitors, glucagon-like peptide-1 receptor agonists, target trial emulation

Introduction: Rapid use of GLP-1RAs, including semaglutide and tirzepatide, has raised concerns regarding a potential association with non-arteritic anterior ischemic optic neuropathy (NAION). However, evidence among non-diabetic individuals with obesity remains limited.

Aims: To assess the association between NAION and GLP-1RAs in non-diabetic individuals with obesity.

Methods: The retrospective cohort study used TriNetX global network, including individuals aged ≥20 years with BMI ≥30 kg/m² and no prior diagnosis of DM within 3 years who initiated tirzepatide, semaglutide, or traditional anti-obesity medications (AOMs) between January 1, 2022, and March 31, 2025. We defined index date as the date of first prescription. Individuals with prior study-drug exposure, optic nerve disorders, relevant systemic diseases, or contraindications one year before the index date were excluded. The primary outcome was incident NAION. To mimic randomization, we applied 1:1 propensity score matching using baseline characteristics, including metabolic parameters, comorbidities, and co-medications. We used the Cox proportional hazards models to generate hazard ratios (HR) and 95% confidence intervals. Sensitivity analyses included HbA1c <6.0% restriction, and conjunctivitis as a negative control outcome.

Results: We identified 163,790 tirzepatide initiators, 420,543 semaglutide initiators, and 153,187 AOMs initiators. Baseline characteristics were well balanced after PS matching. Compared with AOMs, tirzepatide (HR, 2.97;1.66-5.31) and semaglutide (HR, 3.42;2.10-5.58) were associated with an increased risk of NAION. These associations were attenuated toward the null (HR, 1.36;0.62–2.96 for tirzepatide; HR, 1.76;0.91–3.41 for semaglutide) following PS matching, including age, sex, comorbidities, and HbA1c. Findings were consistent after HbA1c restriction.

Conclusions: Both tirzepatide and semaglutide were associated with an increased risk of NAION among non-diabetic individuals with obesity, though the association attenuated toward the null after PS matching. This suggested residual differences in baseline health status, such as age, sex, comorbidities, or abnormal metabolic profiles, may partially explain the observed association between GLP-1RAs and NAION.

Introduction: Glycemic control among patients with type 2 diabetes mellitus (T2DM) is heterogeneous, and average HbA1c values may not adequately reflect long-term glycemic patterns. Identifying HbA1c trajectories and associated factors may support individualized diabetes management.

Aims: To identify distinct HbA1c trajectory patterns among Thai patients with newly diagnosed T2DM and evaluate factors associated with longitudinal HbA1c levels.

Methods: This retrospective population-based cohort study used the Thai Ministry of Public Health 43-file national health database from 2017 to 2025. Adults newly diagnosed with T2DM during 2017–2019 with at least four HbA1c measurements and five years of follow-up were included. Group-based trajectory modeling was used to identify longitudinal HbA1c patterns. A time-lagged generalized estimating equation model with robust standard errors evaluated demographic, clinical, and treatment-related factors associated with repeated HbA1c levels. Missing BMI and blood pressure values, accounting for approximately 3.8% of repeated observations in the longitudinal dataset, were handled using multiple imputation with 20 imputed datasets.

Results: Among 106,005 patients, three HbA1c trajectories were identified: stable glycemic control (80.4%), poor glycemic control with partial improvement (16.1%), and persistently very poor glycemic control (3.5%). In the time-lagged GEE analysis, female sex, younger age, smoking, high comorbidity burden, higher diastolic blood pressure, and prior insulin use were associated with higher longitudinal HbA1c levels. Greater antidiabetic medication burden at the previous visit, higher BMI, higher systolic blood pressure, and alcohol use were associated with lower HbA1c levels.

Conclusions: Distinct HbA1c trajectories were identified among Thai patients with newly diagnosed T2DM, with approximately one-fifth showing poor or persistently very poor glycemic control. Demographic, clinical, and treatment-related factors were associated with longitudinal HbA1c levels, supporting early risk stratification and individualized follow-up.

Keywords: Type 2 diabetes mellitus; HbA1c; glycemic control; trajectory analysis; Thailand

Introduction: The risk of type 2 diabetes mellitus (T2DM) regarding finasteride and tamsulosin remains controversial.

Aims: To investigate the incidence of T2DM in finasteride and tamsulosin users among China and UK populations.

Methods: Using Exchange Xiamen PLatform Of Resident E-health Records (EXPLORER) in China and UK Biobank (UKB), this study included men aged 40-80 years diagnosed with benign prostatic hyperplasia. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using Cox models, incorporating propensity score-based overlap weighting and inverse probability of censoring weighting. The covariates included age, race, smoking status, alcohol consumption, physical activity, socioeconomic status, educational attainment, marital or cohabitation status, dietary habits, healthcare utilization, comorbidities, and medication use.

Results: The EXPLORER cohort comprised 34,075 patients, with 21,399 untreated, 2,122 on finasteride alone, 5,012 on tamsulosin alone, and 5,542 on combination. The UKB cohort comprised 11,905 patients, with 7,050 untreated, 492 on finasteride alone, 3,105 on tamsulosin alone, and 1,258 on combination. Both cohorts showed satisfactory group balance post-weighting (standardized mean differences [SMD]<0.1). Compared to patients receiving tamsulosin alone, those receiving finasteride alone showed a higher T2DM risk (HR = 1.36 [95% CI 1.15-1.60] in EXPLORER; 1.32 [0.96-1.82] in UKB). When compared to non-treatment, finasteride monotherapy was not associated with an elevated T2DM risk (1.00 [0.89-1.13] in EXPLORER; 1.04 [0.77-1.41] in UKB), whereas tamsulosin monotherapy and combination therapy were associated with a reduced T2DM risk (0.71 [0.64-0.80] and 0.44 [0.40-0.49] in EXPLORER; 0.67 [0.56-0.81] and 0.45 [0.34-0.59] in UKB).

Conclusions: Tamsulosin treatment, with or without finasteride, was associated with a lower risk of developing T2DM. In contrast, finasteride users showed a higher T2DM risk than tamsulosin users, particularly among the Asian population. The potential benefits of tamsulosin against T2DM require further investigation, and clinicians may consider regular assessment of T2DM risk in patients using finasteride.