This study evaluated the efficacy and safety of generic semaglutide compared with innovator Semaglutide in Indian adults with type 2 diabetes mellitus (T2DM).

This Phase 3, multicenter, randomized, active-controlled, non-inferiority trial enrolled 320 adults with T2DM inadequately controlled on metformin. Participants were randomized 1:1 to receive either generic semaglutide (Alkem laboratories Ltd.) or innovator Inj. semaglutide (Novo Nordisk) for 24 weeks in step-wise dose escalation from 0.25 mg/week to 2 mg/week. The primary endpoint was change in HbA1c from baseline to Week 24. Secondary endpoints included changes in fasting and post-prandial glucose, body weight, and proportion of patients achieving HbA1c < 7.0%. Safety assessments included adverse events, hypoglycemia, various laboratory parameters.

Of 320 participants randomized, 313 completed the study. Baseline demographic and clinical characteristics were comparable between groups. At Week 24, both treatments achieved significant HbA1c reductions (mean - 2.20%), with generic semaglutide demonstrating non-inferiority to the reference. Reductions in body weight, fasting and post-prandial glucose were similar between arms. A total of 86.62% of participants achieved HbA1c < 7.0%. Safety profiles were comparable, with predominantly mild-to-moderate adverse events and no treatment-related serious adverse events.

Generic semaglutide demonstrated non-inferior efficacy and comparable safety to innovator Semaglutide in Indian adults with T2DM inadequately controlled on metformin, offering an effective and accessible therapeutic option in resource-limited settings.

Diabetes mellitus is strongly associated with peripheral arterial disease and foot ulceration, frequently requiring revascularisation to promote wound healing. Percutaneous transluminal angioplasty (PTA) is widely used for infrapopliteal arterial disease; however, its effectiveness for ulcer healing compared with alternative strategies remains uncertain.

To assess the effects of PTA in infrapopliteal arterial disease for diabetic ulcer healing.

We conducted a systematic review of randomised controlled trials identified through MEDLINE, Embase, LILACS, CENTRAL, CINAHL, ClinicalTrials.gov, the World Health Organisation International Clinical Trials Registry Platform, and grey literature sources. Study selection and data extraction were performed independently. Risk of bias was assessed using the Cochrane Risk of Bias tool. Meta-analyses were undertaken where appropriate, and certainty of evidence was evaluated.

Of 34 542 records screened, six randomised controlled trials (945 total participants) were included. Compared with venous bypass, PTA was associated with a higher likelihood of ulcer healing (risk ratio 1.20; 95% confidence interval 1.07-1.33; p = .0001; low-certainty evidence). No statistically significant differences were observed between revascularisation strategies for mortality or major amputation. Similarly, no significant differences were identified in comparisons of PTA versus drug-coated balloon or drug-coated stent interventions.

PTA may be associated with improved arterial ulcer healing compared with venous bypass in patients with diabetes, without clear differences in mortality or amputation rates. However, the certainty of evidence is low, and these findings should be interpreted with caution. Further adequately powered randomised trials are required to clarify the comparative effectiveness of infrapopliteal revascularisation strategies.

Adults with diabetes mellitus (DM) and poor social vulnerability index (SVI) have been shown to have worse clinical outcomes with uncontrolled DM. Patient assistance programs (PAPs), free clinics, and charitable medication programs have been shown to improve hemoglobin A1C (HbA1c) for uninsured adults.

The primary objective of this study was to evaluate the impact of a charitable medication program on HbA1c as well as other clinical outcomes [blood pressure (BP), low-density lipoprotein (LDL) and body mass index (BMI)] in adults with type 2 diabetes mellitus (T2DM). Secondly, this study aimed to evaluate the impact of SVI on patient follow-up practices.

This retrospective chart review evaluated patients who were dispensed any T2DM-related medication from the Healthy Connections Medication (HCM) program at Hackensack Meridian Health (HMH) pharmacies from January 1st, 2023, to December 31st, 2024. Clinical outcomes were measured at baseline (30 days within fill date) and again within 6 months from baseline. All included and excluded patients' SVI were measured to determine vulnerability.

Of 624 patients with T2DM medications, 87 met inclusion criteria. Statistically significant improvements were observed in HbA1c (11.30% to 9.60%; p < 0.001) and BP (SBP: 128 to 123 mmHg, p = 0.002; DBP: 78 to 75 mmHg, p = 0.005). Median LDL and BMI also decreased from baseline but missed statistical significance. Patients who did not have a repeat HbA1C within 6 months had a higher SVI (0.51 vs 0.45, p=0.01).

Healthy Connections Medications improved all clinical outcomes with statistically significant reductions in HbA1c and BP within 6 months. Patients who did not obtain a repeat HbA1c had a higher SVI which may indicate a greater vulnerability among those patients who did not follow-up. Future studies should examine the implications of SVI and patient follow-up.

To evaluate the association of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) use on macrovascular and microvascular outcomes in patients with type 2 diabetes (T2D) and diabetic retinopathy (DR)-a high-risk group often excluded from clinical trials.

Retrospective, population-based cohort study.

Adults aged ≥18 years with T2D (with hemoglobin A1c of ≥6.5%) and a pre-existing diagnosis of DR from the TriNetX research network database between January 1, 2015, and December 31, 2022.

The study included 173,216 adults with T2D, all of whom had DR, adjusted for baseline characteristics through propensity score matching (PSM) based on whether the individuals received at least two prescriptions of a GLP-1 RA (semaglutide, dulaglutide, liraglutide, exenatide, tirzepatide, or lixisenatide) at least six months apart.

Cox proportional hazard regression models were used to evaluate the association between GLP-1 RAs and the risk of incident macrovascular and microvascular complications over a two-year follow-up period.

After PSM, 30,613 individuals (mean [SD] age, 61.6 [11.4] years; 53.2% were females) were prescribed GLP-1 RAs. Patients on GLP-1 RAs had a decreased risk of myocardial infarctions (MIs; hazard ratio [HR], 0.65; 95% CI, 0.61-0.69), coronary artery revascularization procedures (HR, 0.75; 95% CI, 0.67-0.84), heart failure exacerbations (HR, 0.78; 95% CI, 0.76-0.81), ischemic strokes (HR, 0.78; 95% CI, 0.74-0.83), lower extremity amputations (HR, 0.78; 95% CI, 0.69-0.88), acute kidney injuries (AKI; HR, 0.68; 95% CI, 0.66-0.71), or the need for renal replacement therapy (RRT; HR, 0.40; 95% CI, 0.36-0.43). Fewer individuals also progressed to proliferative diabetic retinopathy (HR, 0.78; 95% CI, 0.71-0.86), experienced retinal vein occlusions (RVOs; HR, 0.70; 95% CI, 0.61-0.80), or developed neovascular glaucoma (HR, 0.65; 95% CI, 0.47-0.89); no association was observed for retinal artery occlusions (RAOs; HR, 0.85; 95% CI, 0.57-1.26) or cases of non-arteritic ischemic optic neuropathy (NAION; HR, 0.88; 95% CI, 0.54-1.44).

In patients with T2D and pre-existing DR, the use of GLP-1 RAs was associated with a reduced risk of major macrovascular and microvascular complications, including those directly affecting the retina. Future studies are needed to assess the extent to which GLP-1 RAs benefit long-term outcomes.

Comorbid major depressive disorder (MDD) and type 2 diabetes mellitus (T2DM) are associated with accelerated cognitive impairment, potentially involving shared immunometabolic and inflammatory mechanisms. The triglyceride-glucose (TyG) index, a surrogate of insulin resistance, has been linked to inflammation. This study examined whether peripheral inflammation statistically mediates the association between TyG and cognitive impairment in patients with comorbid MDD and T2DM.

In this cross-sectional study, 256 patients with MDD and T2DM were enrolled. Cognitive impairment was defined as MoCA <26. Peripheral inflammatory markers (CRP, IL-6, TNF-α) and plasma Alzheimer's disease-related biomarkers (Aβ42/40 ratio, p-tau217) were measured. Multivariable logistic regression and mediation analyses were conducted with adjustment for relevant covariates.

Cognitive impairment was present in 59.37% of participants. Patients with impairment had higher TyG and inflammatory markers (all P < 0.001). TyG was independently associated with cognitive impairment (OR = 2.87, 95% CI: 1.68-4.91). TyG correlated with CRP, IL-6, and TNF-α (r = 0.35-0.42). Peripheral inflammation statistically mediated 28.41% of the TyG-cognition association. Impaired patients showed lower Aβ42/40 and higher p-tau217 (P < 0.001). Serial mediation suggested an indirect association via inflammation and p-tau217 (β = 0.10, 95% CI: 0.03-0.22), accounting for 12% of the total association.

Higher TyG index was statistically associated with cognitive impairment in comorbid MDD and T2DM, partly mediated by peripheral inflammation. While these cross-sectional findings highlight the potential of TyG as an accessible biomarker, longitudinal studies are needed to establish causality and directionality.

Exposure to individual neonicotinoids (NNIs) suggestively correlates with the type 2 diabetes mellitus (T2DM) risk in animals. However, existing systematic epidemiological investigations remain scarce and lack inclusion of predictive biological markers.

This study aimed to evaluate the associations between exposure to NNI and diabetes, and to identify potential biomarkers by developing predictive models.

We enrolled 1119 older individuals from community health screenings and categorized them into three groups: diabetes (n = 224), prediabetes (n = 184), and controls (n = 706). Serum levels of 15 NNIs and their metabolites were measured. Generalized linear models were used to assess correlations between the exposure to individual NNIs and T2DM and prediabetes (PDM). Quantile gcomputation (qgcomp), Bayesian kernel machine regression (BKMR) models, and weighted quantile sum regression were utilized to investigate the correlations between NNI mixtures and T2DM and PDM risks. Untargeted metabolomics was performed to examine relevant metabolites in the NNI-induced T2DM. Targeted metabolomics were then quantified. Mediation analysis was conducted to examine whether amino acid metabolism mediates the observed associations, and a prediction model was established to assess the risk of diabetes owing to NNI exposure.

The detection rates of most NNI pesticides exceeded 90%, with the highest reaching 99.55%. The qgcomp data showed that 6-chloronicotinic acid contributed most significantly to T2DM, whereas thiacloprid-amide (THD-A) showed the strongest contribution to PDM. BKMR models indicated that co-exposure to multiple NNIs increase the risk of developing both T2DM and PDM. Non-targeted metabolomics revealed that the tryptophan (Trp) metabolic pathway mediates the development of diabetes mellitus, with kynurenine (KYN)-mediated THD association with T2DM showing the largest proportion of mediation at 24.93%. A predictive model for NNI-diabetes was developed by incorporating KYN, tryptamine, xanthurenic acid, and the body mass index. An 80.4% consistency rate was determined between predicted and actual probabilities.

This study reveals a dose-dependent association between neonicotinoid exposure and diabetes in older adults, accompanied by disturbances in tryptophan metabolite profiles. These findings provide new evidence for global research on the metabolic toxicity of environmental neonicotinoids and international public health risk assessment.

Adolescence is marked by significant physiological and psychological changes that can lead to body image dissatisfaction and eating disorders (ED). Adolescents with type 1 diabetes mellitus (T1DM) may engage in restrictive dieting or insulin manipulation to control weight, risking severe complications. This study aims to identify adolescents with T1DM at risk for diabetes-specific eating behaviors using the Diabetes-Specific Eating Problems Scale-Revised (DEPS-R) and assess associated psychopathological factors, including diabulimia.

Adolescents (10-18 years) with T1DM who were under follow-up in our clinic within the past year were included. Patients were categorized into 3 metabolic control groups according to HbA1c levels: good (<7%), moderate (7-9%), and poor (>9%) based on the cumulative glycemic index that was calculated from the average HbA1c values over the past year. Eating behaviors were assessed using the DEPS-R scale, with scores≥20 indicating risk for ED. Individuals with high DEPS-R scores (at-risk group) were referred for psychiatric evaluation.

A total of 11.2% our of 80 adolescents, were identified as at risk for EDs. The mean DEPS-R score of the at-risk group was significantly higher vs the other group (25.8±3.5 vs 10.0±4.6, p<0.001). No significant differences were observed for age, gender, height SDS, and relative BMI. Although the at-risk group had a higher cumulative glycemic index and longer diabetes duration, there was no statistical significance (p=0.29, 0.28, respectively). Logistic regression analysis, adjusted for age, sex, diabetes duration, and comorbidities, did not identify statistically significant predictors of high DEPS-R scores. A weak positive correlation was found between high DEPS-R scores and basal-bolus insulin therapy (r=0.09, p=0.03). Psychopathology was observed in 55% of high-risk adolescents, with a higher prevalence in the poor metabolic control subgroup.

Although the DEPS-R scale is a valuable tool for identifying not only EDs but also early changes in eating behaviors in adolescents with T1DM, psychiatric evaluation is essential for confirming underlying psychopathology. Psychological factors play a key role in shaping eating behaviors, highlighting the need for integrated care combining diabetes management with psychological support.

To investigate whether cataract surgery is a risk factor for developing new-onset thyroid eye disease in patients with preexisting thyroid disorders using a large, population-level database.

The study utilized a large database of deidentified electronic health records. Patients who underwent cataract extraction were divided into 2 cohorts and were balanced using propensity score matching for demographic factors and comorbidities, including age, sex, race, diabetes mellitus, hyperlipidemia, and nicotine dependence. The incidence of thyroid eye disease-related outcomes was assessed at 3-time intervals following the surgery date: up to 3 months, 3-6 months, and 6-12 months. The need for orbital decompression surgery was also assessed. A secondary sensitivity analysis was conducted for patients with hyperthyroidism.

After propensity score matching, 87,179 pairs were analyzed. Patients with thyroid disease had a significantly higher risk for the composite thyroid eye disease outcome at all time intervals: 0-3 months (risk ratio [RR]: 1.30, 95% confidence interval [CI]: 1.12-1.51), 3-6 months (RR: 1.30, 95% CI: 1.12-1.51), and 6-12 months (RR: 1.51, 95% CI: 1.33-1.71). The risk was even more pronounced in the hyperthyroid subgroup (n = 8,381), reaching a 103% increased risk at 6-12 months (RR: 2.03, 95% CI: 1.39-2.95). While no significant difference was observed for orbital decompression surgery in the immediate postoperative period, a significantly increased risk emerged at the 6-12-month interval (RR: 1.59, 95% CI: 1.13-2.24).

Cataract surgery is associated with a significantly increased risk of developing thyroid eye disease-related outcomes in patients with underlying thyroid disease. While the overall incidence may be low, the potential consequences can be serious, highlighting the importance of clinical awareness, patient counseling, and close postoperative monitoring for this at-risk population.

Genetic mechanisms that predispose people to type 2 diabetes (T2D) and cardiovascular disease (CVD) remain poorly understood, partly because of a lack of sufficient data on non-European ethnic groups. Extending these evaluations to diverse cohorts is essential for gaining insights into the molecular pathways involved in disease development among human populations. In this study, we aimed to evaluate the genetic connection between the human lipidome and cardiometabolic disorders. We conducted a metabolite genome-wide association study (mGWAS) in a Punjabi population from India, along with multi-layer replication studies using the UK Biobank and other independent European and non-European cohorts.

We performed mGWAS using 516 lipid metabolites in 3,000 Punjabi Sikh individuals, and validation was performed in 1.13M Europeans and 15K individuals from Asian Indian ancestry using independent cohorts of the UK Biobank, GeneRISK, DIAMANT, PROMIS, and other studies. We identified 609 SNP-metabolite associations representing 236 SNP-metabolite pairs that attained genome-wide significance (p </= 5 × 10-8). Of the 36 SNP-lipid metabolite signals that survived multiple testing correction (p </= 1.92 × 10-10), 33 associations were not reported before, and 3 associations were confirmed to be ancestry-specific. Using colocalization analysis, polygenic risk scores, and mendelian randomization approaches, we identified a causal association of LPC O-16:0 with T2D, represented by a lead variant in CD45, a key regulator of T- and B-cell antigen receptor signaling, and is already used as a therapeutic target. Another possible causal relationship of PC 38:4 (C) in protecting against coronary artery disease risk in Asian Indians, attributed to a variant in the untranslated region in the FADS1/2 genes, may be specific to ancestry and/or could not be confirmed in Europeans because of extensive pleiotropy in this region. The main limitation of this study was the absence of an independent validation cohort of Asian Indians from India.

The mGWAS of Asian Indians offers new insights into the diverse molecular origins of cardiometabolic diseases and suggests potential pathways for innovative treatments. Our findings highlight the need for additional research on human lipidomics to better understand the downstream effects of the genome and its impact on cardiometabolic health.