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PubMed2026

Efficacy and Safety of the Dual Glucagon-Like Peptide-1 and Glucagon Receptor Agonist Mazdutide in Predominantly Chinese Adults With Obesity and/or Type 2 Diabetes: A Systematic Review and Meta-Analysis.

AIM: To assess the effects of mazdutide on body weight, HbA1c, metabolic outcomes, and adverse events in adults with overweight/obesity and/or type 2 diabetes (T2D). METHODS: This systematic review and meta-analysis included randomized controlled trials (RCTs) comparing mazdutide with placebo or active comparators in adults with overweight/obesity and/or T2D, identified through PubMed, Scopus, Web of Science, and ClinicalTrials.gov to 20 February 2026. Co-primary outcomes were percent change in body weight and change in HbA1c. Secondary outcomes included other weight-related and metabolic outcomes, as well as safety. Random-effects models were used to generate pooled mean differences (MDs) or risk ratios with 95% confidence intervals, and the certainty of the evidence (COE) was assessed using GRADE. RESULTS: Nine RCTs (N = 2292; most with low risk of bias) were included. In overweight/obesity without diabetes, mazdutide 3, 4, and 6 mg reduced body weight more than placebo (MDs -6.56%, -9.92%, and -11.1%, respectively; very low COE due to substantial heterogeneity and few trials). In T2D, mazdutide 4 and 6 mg reduced body weight and HbA1c versus placebo (moderate COE) and also outperformed dulaglutide for both outcomes. Mazdutide also improved waist circumference, lipids, liver enzymes, and uric acid levels. Gastrointestinal adverse events were more frequent, but serious adverse events and treatment discontinuation rates were comparable with those of the comparators. CONCLUSIONS: Mazdutide was associated with dose-dependent reductions in body weight and HbA1c, with broader metabolic benefits in predominantly Chinese adults with obesity and/or T2D. Longer-term, multi-ethnic studies are needed to confirm durability, generalizability, and cardiovascular safety.

Humans↗

PubMed2026

Construction of precision clinical-proteomics risk model based on machine learning for predicting heart failure in type II diabetes mellitus.

BACKGROUND AND AIMS: Heart failure (HF) is a severe complication in type 2 diabetes mellitus (T2DM), but current risk stratification scores have limited predictive accuracy. We aimed to develop novel prediction tools integrating clinical variables with proteomics to improve risk stratification of hospitalization for HF in T2DM. METHODS AND RESULTS: In this study, we included 2111 UK Biobank participants with T2DM but no prior HF, and profiled 2920 proteins to predict 10-year incident HF hospitalization. Participants were randomly divided into training (70%), tuning (10%), and validation (20%) sets.Three prediction models were developed: a Clinical model based on demographic characteristics, comorbidities, medication use, and laboratory indices; a Protein model based on 40 proteins selected by the Light Gradient Boosting Machine (LGBM); and the Clinical OMics and Protein ASSessment for Heart Failure (COMPASS-HF) model, which integrated both clinical variables and the LGBM-selected proteins. Models were evaluated for area under the curve (AUC), sensitivity, and specificity. During follow-up, 168 participants (7.96%) developed incident HF. The COMPASS-HF model showed better discrimination than the Clinical model, with an AUC of 0.897 (95% CI: 0.850-0.945) versus 0.790 (95% CI: 0.723-0.856). It also demonstrated higher sensitivity (0.882; 95% CI: 0.725-0.967) and consistent performance in subgroups. COMPASS-HF effectively stratified risk of hospitalization for HF, with cumulative incidence rates of 31.9% in the high-risk group and 1.2% in the low-risk group. CONCLUSIONS: By combining clinical and proteomic variables, we developed a high-performance HF prediction model for T2DM, enabling precise risk stratification and informing early intervention strategies.

Humans↗

PubMed2026

Premeal insulin administration lowers postprandial blood glucose and increases myocardial microvascular blood flow in people with type 1 diabetes: a randomised, crossover clinical trial.

AIMS/HYPOTHESIS: We aimed to evaluate whether prandial insulin timing affects vascular function in people with type 1 diabetes. Our hypothesis was that premeal insulin administration would lead to greater myocardial microvascular blood flow (MBF) via blunting postprandial hyperglycaemia. METHODS: People with type 1 diabetes between 18 and 35 years of age with BMI <30 kg/m2 underwent two protocols with a 1:1 randomised crossover design wherein prandial insulin was injected either 15 min before or 15 min after meal intake began. To provide a physiological comparison, age-, sex- and BMI-matched control participants completed one study where they consumed the same meal but received no exogenous insulin. Glucose, insulin, vascular function (including ultrasound measures of myocardial and skeletal muscle microvascular perfusion, aortic stiffness, brachial artery endothelial function) and biomarkers of systemic inflammation and endothelial dysfunction were assessed at baseline and then 2 h after meal ingestion within each protocol. The primary outcome was change in myocardial MBF within each protocol. Study personnel assessing outcomes were masked to group assignment. RESULTS: Eighteen people with type 1 diabetes and 18 matched control participants were analysed within each protocol. Glucose area under the curve was significantly greater (p=0.015) in the postmeal insulin study compared with the premeal insulin study in participants with type 1 diabetes. Myocardial microvascular flow velocity significantly increased (p=0.031) with premeal insulin administration in people with type 1 diabetes and this consequently led to greater myocardial MBF (p=0.044). There were no changes in myocardial MBF within the other protocols. Changes in vital signs were similar between all protocols. CONCLUSIONS/INTERPRETATION: Appropriately timed premeal insulin led to lower postprandial blood glucose along with increased myocardial MBF in people with type 1 diabetes. Further work is needed to determine the underlying aetiology of these changes. TRIAL REGISTRATION: ClinicalTrials.gov NCT04730882.

Humans↗

PubMed2026

Financial incentives and social messaging for repeat SARS-CoV-2 antibody testing among the underserved: A randomized trial.

Financial incentives may influence health behavior beyond their expected monetary value, and their effectiveness may depend on how the behavior is framed. Behavioral theories of decision making suggest that individuals may value protection against small-stakes losses more than expected utility predicts, while theories of family-centered health behavior suggest that messages emphasizing benefits to family members may strengthen participation in preventive health activities. We tested these ideas in a 2×2 factorial randomized trial involving 625 households recruited from a Federally Qualified Health Center serving low-income Latino/Hispanic communities. Participants completed repeat SARS-CoV-2 antibody testing. The trial crossed two messaging strategies (Family vs. Personal) with two incentive structures (Loss Protection vs. Lottery) that offered equivalent expected monetary value. Family Messaging emphasized protecting one's family from COVID-19, whereas Personal Messaging emphasized protecting oneself. Loss Protection allowed participants to secure an at-risk reward through repeat testing, whereas the Lottery condition offered a chance of a large reward. Repeat testing was approximately 8 percentage points higher under Family Messaging and 7 percentage points higher under Loss Protection. Baseline trust in medical providers, financial barriers to vaccination, and risk aversion were associated with initial testing, whereas household characteristics were not associated with repeat testing. Incentive design may matter beyond expected monetary value and that framing health behaviors in terms of family welfare may increase participation in repeated healthy activities. Broadly, the results support behavioral theories emphasizing loss aversion, anticipated regret, and family-centered motivations, and suggest practical approaches for improving engagement in repeat health behaviors. CLINICALTRIALS.GOV REGISTRATION NUMBER:: NCT01901624.

Adult↗

PubMed2026

Effects of intensive lifestyle interventions with calorie-carbohydrate-restricted diet versus time-restricted eating on appetite and binge eating in type 2 diabetes: A randomized controlled trial.

The impact of intensive lifestyle interventions on appetite regulation and binge eating in individuals with type 2 diabetes (T2D) remains unclear. This study evaluated the effects of combined lifestyle interventions on appetite responses and binge eating in overweight or obese adults with T2D. In a randomized trial, 120 participants with T2D were allocated to three groups (n = 40 each): (1) Calorie-carbohydrate restriction (CCR), (2) Time-restricted eating with CCR (TRE + CCR), or (3) Control. Intervention groups received structured exercise and behavioral education based on the Information-Motivation-Behavioral Skills model. Appetite perceptions (hunger, satiety, desire to eat, and prospective food consumption) and binge eating (Binge Eating Scale; BES and objective binge episodes) were evaluated at baseline, week 12, and week 24 using linear mixed models. Both CCR and TRE + CCR significantly improved subjective appetite compared with the control group at 12 and 24 weeks (all p < 0.01). At 24 weeks, hunger decreased by -24.1 mm (95% CI: -35.8, -12.5) in the CCR group and -32.7 mm (95% CI: -44.2, -21.3) in the TRE + CCR group. Satiety also increased by 21.7 mm (95% CI: 9.46, 33.9) and 29.4 mm (95% CI: 17.4, 41.4), respectively. Significant reductions were observed for desire to eat and prospective food consumption. In contrast, changes in BES and objective binge episodes were not significantly different between groups at any time point. No significant differences were detected between the CCR and the TRE + CCR groups. Intensive lifestyle interventions incorporating CCR or TRE + CCR effectively reduced appetite in adults with T2D but did not significantly affect binge eating. Future research should target individuals with higher baseline BES scores to clarify potential benefits for binge eating behavior.

Humans↗

PubMed2026

Apoptosis protein markers in comorbid type 2 diabetes mellitus and depression; relationships with cognitive performance, incident dementia, and white matter hyperintensities.

Type 2 diabetes mellitus (T2DM) and major depressive disorder (MDD) are reciprocal risk factors, and both elevate dementia risk. Dysregulation of programmed cell death is implicated in T2DM, MDD, and neurodegeneration, but proteomic markers of apoptosis have yet to be studied as dementia predictors in people with T2DM and/or MDD. This study examines apoptosis markers in comorbid T2DM and MDD, and their associations with cognitive, dementia, and neuroimaging outcomes. The retrospective sample (n = 15,765) consisted of UK Biobank participants (MDD only n = 1230; T2DM only n = 3644; comorbid T2DM + MDD n = 721). Individuals with T2DM + MDD comorbidity had poorer cognitive performance, and a higher 15-year dementia incidence (HR = 4.44, 95% CI = [3.23,6.11]). Among 60 apoptosis-related proteins identified by Kyoto Encyclopedia of Genes and Genomes pathway enrichment, 41 were significantly up-regulated in comorbid T2DM + MDD relative to controls, and 4 were higher in the comorbid group than both T2DM alone and MDD alone. Tumor necrosis factor ligand superfamily member 10 (TNFSF10), growth arrest and DNA damage-inducible protein GADD45 beta, tumor necrosis factor ligand superfamily member 6, and RAC-gamma serine/threonine-protein kinase were associated with dementia risk. Nine proteins (e.g. apoptosis-inducing factor 1, mitochondrial, caspase-2, mitogen-activated protein kinase kinase kinase 5, TNFSF10), were associated with white matter hyperintensity volumes in comorbid T2DM + MDD after FDR correction, but none were associated with cognitive performance, atrophy, or white matter microstructural changes. These findings identify peripheral apoptosis markers that were further elevated in comorbid T2DM + MDD compared to either alone, pointing to an important pathophysiological element underlying adverse outcomes in the context of mood and metabolic comorbidity.

Humans↗

PubMed2026

Effect of a 6-month low-carbohydrate diet on the circulating fatty acid composition in patients with type 2 diabetes: a secondary analysis of an open-label randomized controlled trial.

BACKGROUND: Circulating fatty acid profiles are linked to cardiovascular disease risk and mortality. Short-term interventions suggest that low-carbohydrate diets (LCDs) promote cardioprotective shifts in circulating fatty acids in obesity. OBJECTIVES: We examined whether a 6-mo, non-calorie-restricted, LCD high in fat similarly improves circulating fatty acid composition in adults with type 2 diabetes. METHODS: In an open-label, randomized, controlled trial, 71 individuals with type 2 diabetes were randomly assigned 2:1 to an LCD [maximum of 20 E% (energy per cent) carbohydrates] or a control diet (50-60 E% carbohydrates) for 6 mo with no restriction in energy intake. The prespecified secondary outcomes were the mean difference in change between groups in serum phospholipid fatty acids in weight percentage (wt%) measured by gas chromatography and reported as 95% confidence intervals (CIs) and significance adjusted for multiple comparisons (q value). RESULTS: LCD reduced total saturated [-0.6 (CI: -0.9, -0.2)] and monounsaturated fatty acids [-0.9 (CI: -1.4, -0.3)] and increased total polyunsaturated fatty acids [1.3 (CI: 0.6, 2.0)] compared with the control diet (all q < 0.05). Importantly, LCD reduced palmitoleic acid (16:1n-7) [-0.13 (CI: -0.21, -0.06)], a marker of de novo lipogenesis, by 23% and dihomo-γ-linolenic acid (20:3n-6) [-0.38 (CI: -0.67, -0.09)] by 12%, whereas it increased arachidonic acid (20:4n-6) [1.1 (CI: 0.3, 2.0)] by 9% compared with the control diet (all q < 0.05). Moreover, the LCD improved estimated desaturase activities by lowering stearoyl-coenzyme A desaturase 1 [-0.5 (CI: -0.7, -0.2)] and Δ6 desaturase [-0.6 (CI: -0.9, -0.2)] and increasing Δ5 desaturase [1.05 (CI: 0.3, 1.79)] activities, respectively (all q < 0.01). These changes occurred despite a 2.6-fold higher intake of saturated fatty acids in the LCD group. CONCLUSIONS: A 6-mo, non-calorie-restricted LCD modified the circulating composition of fatty acids in adults with type 2 diabetes in a manner consistent with a potentially favorable cardioprotective profile. This trial was registered at www. CLINICALTRIALS: gov as NCT03068078.

Humans↗

PubMed2026

Safety and efficacy of recombinant botulinum toxin type A (Eveotox®) in patients with post-stroke upper limb spasticity: Results from a Phase Ib/II clinical trial.

Upper limb spasticity is a common and disabling complication of stroke. Botulinum toxin type A (BoNT-A) is widely used for focal spasticity treatment, but naturally derived products may present limitations related to immunogenicity and manufacturing variability. Recombinant botulinum toxin type A, produced by genetic engineering without complexing proteins, may provide improved product consistency. This Ib/II study evaluated the safety, tolerability, and preliminary efficacy of recombinant botulinum toxin type A in adults with post-stroke upper limb spasticity. This multicenter, seamless Ib/II clinical study included an open-label dose-escalation Ib phase and a randomized, double-blind, placebo-controlled II phase. Adult patients with post-stroke upper limb spasticity received a single intramuscular injection of recombinant botulinum toxin type A or placebo. The primary endpoint in Phase II was the change from baseline in the Modified Ashworth Scale (MAS) score of the primary target muscle group at Week 4. Secondary endpoints included MAS and Tardieu scale changes in individual muscle groups, Disability Assessment Scale (DAS), Physician's Global Assessment (PGA), and immunogenicity. The Ib phase showed improvements in MAS, DAS, and PGA, indicating an early efficacy signal. In Phase II, recombinant botulinum toxin type A produced a significant reduction in MAS score of the primary target muscle group at Week 4 compared with placebo, with effects sustained through Week 12. At Week 4, the PGA score in the Eveotox® group showed a statistically significant improvement compared with the placebo group. While MAS and PGA scores showed significant improvement, DAS functional scores did not differ statistically from the placebo group at week 4. The treatment was generally well tolerated, and low incidence of antibodies were observed. Recombinant botulinum toxin type A was safe and effective in reducing post-stroke upper limb spasticity after a single administration. These results support further Phase III clinical evaluation.

Humans↗

PubMed2025

Treatment preference for once-weekly versus once-daily DPP-4 inhibitors in patients with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND/OBJECTIVE: Although once-weekly and once-daily DPP-4 inhibitors have gained widespread market recognition, patient preference differences remain a key focus. This meta-analysis compares treatment preferences for once-weekly versus once-daily DPP-4 inhibitors in T2DM, offering evidence to guide clinical decisions and healthcare policies. METHODS: PubMed, OVID, EBSCO, Web of Science, CNKI, Wanfang, and clinical trial registries were searched up to June 30, 2025. After screening literature against predefined criteria, a systematic review was conducted to compare the effects of once-weekly and once-daily DPP-4 inhibitors on the treatment preferences of patients with T2DM. RESULTS: 8 RCTs with 1,575 participants were analyzed. No significant difference in medication adherence and DTSQ total score between the once-weekly and once-daily groups (p > 0.05). HbA1c percentage (MD = -0.21, 95% CI [-0.42, -0.01], p < 0.05) decreased significantly with once-weekly dosing, while GA and FPG showed no change (p > 0.05), this suggests greater improvement in HbA1c percentage levels following a switch to once-weekly DPP-4 inhibitors. Once-weekly DPP-4 inhibitors showed higher musculoskeletal/connective tissue disorder risk (RR = 2.63; 95% CI [1.18, 5.83]), but no significant differences in other adverse events (p > 0.05). No significant differences in treatment burden between both groups (p > 0.05). CONCLUSION: No statistically significant association between treatment preferences for once-weekly versus once-daily DPP-4 inhibitors among T2DM patients and medication adherence, treatment satisfaction, glycemic level changes, safety, or treatment burden for these two dosing regimens. Further research is needed to elucidate the influence of physician prescribing behavior on these preferences.

Humans↗

PubMed2025

Influence of soil types with different soil-forming process on the qualitative and quantitative detection of microplastics by near-infrared spectroscopy.

Microplastics (MPs) have become a pressing global environmental threat, with soils-acting as sinks for MPs from multiple sources-gaining increasing attention. Near-infrared (NIR) spectroscopy offers a promising tool for MPs detection due to its rapid, non-destructive, and field-applicable features. Although previous studies have focused on the effects of individual soil components on the NIR detection performance of MPs, there is still a lack of systematic research on how the complex background-formed by the coupling of multiple physicochemical properties in natural soils-affects detection performance. This study focuses on soil types with different soil-forming processes, selected five representative agricultural soils to systematically evaluate how the combinations of physicochemical properties they represented affect the performance of NIR-based qualitative and quantitative analysis of MPs in soils. The results demonstrated that soil type significantly affected both the spectral response and detection performance of MPs. Brown Pedocals and Brown Earth exhibited clearer characteristic absorption and stronger linear responses, achieving higher identification accuracy under low (<1.5 %) or zero MPs concentrations and the best quantitative performance (R2 ≥ 0.988, prediction set root mean square error (RMSEP) ≤ 0.110 %). In contrast, Phaeozem and Red Soil were more prone to misclassification at low concentrations, while Fluvo-aquic Soil showed the poorest quantitative performance. This study is the first to reveal, at a holistic level, the critical constraints posed by natural soil complexity on the NIR detection of MPs, offering targeted empirical evidence to support the application of NIR technology in real-world soil environments.

Soil↗

PubMed2026

Acute mild cold exposure with shivering reduces 24 h glucose levels in individuals with type 2 diabetes but not prediabetes.

AIMS/HYPOTHESIS: Repeated cold exposure with shivering has been proposed as a potential strategy to enhance glucose metabolism by increasing energy expenditure and substrate utilisation. However, acute effects/benefits of cold-induced shivering on glucose homeostasis in metabolically compromised individuals are unknown. Here, we aimed to determine whether cold exposure at two different intensities improves 24 h glucose homeostasis in individuals with prediabetes and type 2 diabetes. METHODS: In a randomised crossover trial conducted in the South Limburg/Maastricht region of the Netherlands, men and postmenopausal women with prediabetes (n=12) and stable type 2 diabetes (n=12), aged 40-75 years, body mass index ≥27 and ≤35 kg/m2, non-smoking and sedentary, underwent two whole-body cold exposure sessions using a water-perfused suit. Session order was randomised using an online randomisation tool (randomizer.org); participants were masked to the cold exposure intensity received, but investigators were not. Sessions were designed to elicit ~1.5-fold (mild, 15°C) and ~2.5-fold (moderate, 4°C) increases in resting metabolic rate (RMR). Continuous glucose monitoring assessed interstitial glucose concentrations over 24 h periods before and after each intervention, with controlled diet and activity. Shivering was confirmed via indirect calorimetry and electromyography. RESULTS: In both study groups and periods, RMR increased significantly vs baseline (p<0.001 for all). In prediabetes, the increase in the final 1 h of cold was 1.53 × RMR in mild and 1.94 × RMR in moderate cold. In type 2 diabetes, the increase was 1.57 × RMR and 2.09 × RMR in the final 1 h of mild and moderate cold, respectively. In prediabetes, neither mild nor moderate cold exposure altered mean 24 h glucose levels. In contrast, after mild cold exposure the type 2 diabetes group exhibited a significant reduction in mean 24 h glucose levels (-0.6 ± 0.5 mmol/l, p=0.003) and fasting glucose (-0.6 ± 0.8 mmol/l, p=0.019), as well as an increase in time in normal range (+8.8 ± 10.3%, p=0.013) and reduced time in hyperglycaemia (-10.9 ± 12.9%, p=0.014). Moderate cold did not significantly affect any of the glucose outcomes in type 2 diabetes. Baseline fasting glucose, age and ALT levels were predictors of the glucose-lowering response, suggesting greater benefits in individuals who have higher baseline glucose levels, are younger and/or have more optimal liver health, i.e. lower ALT. CONCLUSIONS/INTERPRETATION: Acute mild cold exposure with shivering reduced 24 h glucose levels in individuals with type 2 diabetes. No changes were observed in prediabetes. The observed effects appear to depend on baseline metabolic status rather than acute substrate utilisation during cold exposure. These findings support the potential of cold exposure as an adjunct non-pharmacological therapy for type 2 diabetes, although further mechanistic studies and validation in larger cohorts are warranted. TRIAL REGISTRATION: ClinicalTrials.gov NCT05576025 FUNDING: Dutch Organisation for Knowledge and Innovation in Health, Healthcare and Well-being (ZonMw): 09120012010062.

Humans↗

PubMed2026

Efficacy of dapagliflozin on hepatic steatosis and fibrosis in patients with type 2 diabetes mellitus and metabolic dysfunction-associated steatotic liver disease: a pre-specified single-arm analysis from a randomized controlled trial.

AIM: To evaluate the association of dapagliflozin therapy with changes in hepatic steatosis and non-invasive fibrosis surrogate markers in patients with type 2 diabetes mellitus (T2DM) and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) over 12 months. METHODS: This is a pre-specified single-arm analysis from a randomised, open-label, parallel-group trial. Of 54 participants randomised to dapagliflozin 10 mg daily, 50 (92.6%) completed the 12-month follow-up and were included in the per-protocol analysis. Assessments at baseline, 3, 6, and 12 months included transient elastography (CAP and LSM), ultrasonography, and biochemical tests. Primary endpoints were changes in hepatic steatosis (CAP) and non-invasive fibrosis surrogates (LSM). RESULTS: Significant reductions were observed in hepatic steatosis (CAP: 316.7 to 245.7 dB/m; mean change - 71.02 dB/m, 95% CI: -63.4 to - 78.6; p < 0.001) and in liver stiffness as a non-invasive fibrosis surrogate (LSM: 8.59 to 7.28 kPa; mean change - 1.31 kPa, 95% CI: -0.92 to - 1.70; p < 0.001). Improvements were also observed in glycaemic control, body weight, lipid profile, liver enzymes, ultrasonographic steatosis grading, and serum fibrosis markers. Genitourinary infections were the most frequently reported adverse events (32%); no serious adverse events were recorded. CONCLUSIONS: Dapagliflozin was associated with significant improvements in hepatic steatosis, non-invasive fibrosis surrogate markers, metabolic parameters, and liver function in T2DM patients with MASLD over 12 months. These findings provide region-specific evidence for an Indian population and support further controlled investigation. However, these findings should be interpreted in light of the pre-specified single-arm design of this analysis, the open-label methodology, relatively small sample size, and the absence of liver biopsy confirmation.

Humans↗

PubMed2026

Reported exposure to news portrayals about mental health problems and their impact: Findings from the 2025 National Survey of Stigma and Discrimination.

OBJECTIVE: Media portrayals of people with mental illness have the power to mitigate or perpetuate stigma related to mental health. This study aimed to investigate reported real-world exposure to news media portrayals about people with mental health problems in the past 12 months and the impact of these. METHODS: Data were from a nationally representative survey of 6032 Australians exploring attitudes towards people with mental health problems. Participants were asked about their exposure to positive news stories about a person with a mental health problem, as well as negative portrayals, in which someone was harmed by a person with a mental health problem. Further questions covered the sources (traditional or social media) and impact of these exposures. RESULTS: Regression models were used to explore sociodemographic predictors of impact. Most participants reported exposure to negative news portrayals (68.4%, 95% confidence interval = [66.9, 69.8]), while fewer reported exposure to positive news stories (33.7%, 95% confidence interval = [32.3, 35.2]). Most people exposed to the negative news stories reported a negative impact (69.0%, 95% confidence interval = [67.2, 70.7]), and most exposed to positive news stories reported a positive impact (80.2%, 95% confidence interval = [77.6, 82.5]). Age and gender were associated with reported impact but not lived experience of mental illness. CONCLUSIONS: Exposure to negative news stories about mental health problems was prevalent. Given their impact on news audiences broadly, negative news stories need to be accurate and responsible to mitigate negative impacts. A renewed focus on generating and promoting positive and stigma-challenging news stories is needed to increase subsequent positive impacts.

Humans↗

PubMed2026

Efficacy and Safety of iGlarLixi Versus IDegAsp by Baseline Age, Disease Duration and HbA1c in Chinese People With Type 2 Diabetes: Post Hoc Analyses of the Soli-D Study.

AIMS: To compare the efficacy and safety of insulin glargine 100 U/mL plus lixisenatide (iGlarLixi) with insulin degludec plus insulin aspart (IDegAsp) by baseline age, Type 2 diabetes (T2D) duration and glycated haemoglobin (HbA1c) in the Soli-D study. MATERIALS AND METHODS: In Soli-D, Chinese adults with T2D suboptimally controlled on oral antidiabetic drugs (OADs) were randomized to iGlarLixi or IDegAsp for 24 weeks. These post hoc analyses evaluated glycaemic efficacy, insulin dose, body weight and hypoglycaemia outcomes in subgroups defined by baseline age (< 65, ≥ 65 years), T2D duration (< 10, ≥ 10 years) and HbA1c (≥ 7% to ≤ 8% [≥ 53 to ≤ 64 mmol/mol], > 8% to ≤ 9% [> 64 to ≤ 75 mmol/mol], > 9% [> 75 mmol/mol]). RESULTS: Among 582 participants (iGlarLixi n = 291; IDegAsp n = 291), baseline age was < 65 years in 442 and ≥ 65 years in 140; T2D duration was < 10 years in 366 and ≥ 10 years in 216; and HbA1c was ≥ 7% to ≤ 8% in 205, > 8% to ≤ 9% in 209 and > 9% in 168. At Week 24, HbA1c reductions were greater with iGlarLixi versus IDegAsp, with no treatment-by-subgroup interactions for baseline age, T2D duration or HbA1c. Change in other glycaemic outcomes, insulin dose and body weight generally showed no interaction across subgroups. Total insulin daily doses during treatment and hypoglycaemia event rates were consistently lower with iGlarLixi versus IDegAsp in all subgroups. CONCLUSIONS: iGlarLixi provides improved glycaemic control at lower insulin doses with reduced risk of hypoglycaemia in Chinese adults with suboptimally controlled T2D on OADs, regardless of baseline age, disease duration or HbA1c.

Humans↗

PubMed2026

Digital Structured Education With Behavioral Nudge Tools for Adults With Type 2 Diabetes: Multicenter Randomized Controlled Trial.

BACKGROUND: Digital interventions offer scalable alternatives to traditional face-to-face diabetes education, but often face challenges related to inconsistent clinical effectiveness, and declining user engagement. However, whether a digital structured education program integrated with behavioral nudge tools can improve metabolic, behavioral, and psychological outcomes in adults with type 2 diabetes remains unclear. OBJECTIVE: This study aimed to evaluate the effectiveness of a digital structured education program integrated with behavioral nudge tools in improving metabolic, behavioral, and psychological outcomes among adults with type 2 diabetes. METHODS: This multicenter randomized controlled trial was conducted in the endocrinology departments of 4 hospitals in China. Adults with type 2 diabetes were randomly assigned to an intervention group receiving a digital structured education program integrated with behavioral nudge tools (n=146) or a control group receiving standard digital diabetes education (n=147). Assessments were conducted at baseline and 12-week follow-up. The primary outcome was hemoglobin A1c (HbA1c) at 12 weeks, adjusted for baseline HbA1c, and study center. Secondary outcomes included fasting blood glucose (FBG), weight, BMI, waist circumference, blood pressure, lipid profiles, self-management behaviors, self-efficacy, and habit strength. RESULTS: Among 293 participants (mean age 49.19, SD 10.02 y), 287 (97.9%) completed follow-up. At 12 weeks, the intervention group demonstrated significantly greater improvements than the control group in HbA1c (adjusted mean difference -0.38%, 95% CI -0.68% to -0.09%; P=.01), FBG (adjusted mean difference -0.75, 95% CI -1.27 to -0.44 mmol/L; P<.001), weight (adjusted mean difference -0.84, 95% CI -1.61 to -0.07 kg; P=.03), BMI (adjusted mean difference -0.38, 95% CI -0.65 to -0.11 kg/m²; P=.01), systolic blood pressure (adjusted mean difference -2.71, 95% CI -4.62 to -0.79 mm Hg; P=.01), diastolic blood pressure (adjusted mean difference -2.92, 95% CI -4.47 to -1.37 mm Hg; P<.001), and total cholesterol (adjusted mean difference -0.27, 95% CI -0.48 to -0.05 mmol/L; P=.02). The intervention was also associated with significantly greater improvements in self-management behaviors, self-efficacy, and habit strength (all P<.05). CONCLUSIONS: Digital structured education integrated with behavioral nudge tools improved metabolic outcomes and strengthened psychological and behavioral determinants of self-management among adults with type 2 diabetes over a 12-week period. These findings suggest that a digital structured education program integrated with behavioral nudge tools may enhance diabetes self-management beyond standard digital diabetes education. Further studies with longer follow-up and real-world implementation are warranted to evaluate the sustainability, generalizability, and long-term clinical impact of this integrated intervention.

Humans↗

PubMed2026

Efficacy and Hypoglycaemia Outcomes With Once-Weekly IcoSema Versus Comparators in Individuals With Type 2 Diabetes by Kidney and Liver Function: A Post Hoc Analysis of the COMBINE 1-3 Trials.

AIMS: This post hoc analysis of COMBINE 1-3 assessed efficacy and hypoglycaemia outcomes with IcoSema (once-weekly combination therapy of basal insulin icodec and semaglutide [a glucagon-like peptide-1 analogue]) versus comparators in adults with type 2 diabetes (T2D) by kidney and liver function subgroups. MATERIALS AND METHODS: Treatment outcomes were analysed by trial according to kidney (estimated glomerular filtration rate ≥ 90; 60-< 90; 30-< 60; < 30 mL/min/1.73 m2) and liver (total bilirubin ≤ 21 μmol/L or aspartate aminotransferase [AST] ≤ 31/≤ 37 [female/male] U/L; total bilirubin > 21 μmol/L or AST > 31/> 37 [female/male] U/L) function subgroups. RESULTS: In COMBINE 1-3, across kidney and liver function subgroups, there were no statistically significant treatment by subgroup interactions for change in glycated haemoglobin (HbA1c) (baseline to week 52), change in body weight (baseline to week 52) or rates of combined clinically significant or severe hypoglycaemia (not assessed by kidney function for COMBINE 2) (all p > 0.05). There were statistically significant treatment by kidney function subgroup interactions for the achievement of HbA1c < 7.0% without weight gain and without clinically significant or severe hypoglycaemia in COMBINE 3 (p < 0.05) but not COMBINE 1 or 2, and statistically significant treatment by liver function subgroup interactions in COMBINE 1 (p < 0.05) but not COMBINE 2 or 3. For COMBINE 1 and 3, there were statistically significant treatment by kidney function subgroup interactions for mean weekly total insulin dose, but not statistically significant treatment by liver function subgroup interactions. CONCLUSIONS: Efficacy and hypoglycaemia outcomes with IcoSema versus comparators were generally consistent among adults with T2D with mild to moderate kidney impairment or impaired liver function. TRIAL REGISTRATION: The COMBINE 1-3 trials were sponsored by Novo Nordisk and are registered with ClinicalTrials.gov (NCT05352815; NCT05259033; NCT05013229).

Humans↗

PubMed2026

Sodium-glucose cotransporter-2 inhibitors and gastrointestinal neoplasm risk in type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials.

The potential carcinogenic effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors in patients with type 2 diabetes mellitus (T2DM) remain controversial, particularly regarding site-specific gastrointestinal (GI) neoplasms. This systematic review and meta-analysis aimed to determine the relationship between SGLT2 inhibitors and the risk of GI neoplasms in patients with T2DM. We searched PubMed, EMBASE, Cochrane CENTRAL, Scopus, and Web of Science through March 17, 2025, for RCTs in T2DM comparing SGLT2 inhibitors with placebo or active comparators. Two reviewers independently screened studies, extracted data, and assessed the risk of bias. The primary outcome was GI neoplasms reported in publications, supplementary materials, or trial registries, usually as adverse events rather than centrally adjudicated cancer endpoints. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated in Stata 17.0. In 48 RCTs (n = 48,765), SGLT2 inhibitor therapy was not associated with overall GI neoplasm risk (OR = 1.10, 95% CI: 0.84-1.44; p = 0.46; I² = 0%). Site-specific analyses showed no statistically significant association for esophageal (OR = 1.12, 95% CI 0.37-3.45), gastric (1.20, 0.65-2.23), hepatic (0.62, 0.31-1.22), pancreatic (0.91, 0.51-1.64), colonic (1.28, 0.78-2.08), colorectal (0.76, 0.27-2.17), and rectal neoplasms (0.98, 0.49-1.97), with all p-values > 0.05. Subgroup analyses by agents (e.g., canagliflozin, dapagliflozin, empagliflozin), baseline age, body mass index (BMI), HbA1c, treatment duration, and dose were also non-significant (all p > 0.05). Approximately half of the trials had follow-up of one year or less, limiting our ability to evaluate long-term risk. Available RCT evidence does not show a clear increase in GI neoplasm risk with SGLT2 inhibitors in T2DM. However, limited follow-up, low event counts, and non-cancer-specific outcome ascertainment, the findings should be interpreted as reassuring but not definitive evidence of long-term oncologic safety.Systematic review registration: PROSPERO No. CRD42024619019.

Humans↗

PubMed2026

Genome-wide characterisation of the myosin light chain gene family in Chinese perch (Siniperca chuatsi) and its expression patterns in muscle fibre types and injury response.

The Class II myosin light chain (myl) genes in Chinese perch (Siniperca chuatsi) have not yet been systematically characterised, and relationships with muscle fibre specification, development, and injury-associated remodelling remain unclear. In this study, fast and slow muscle fibres were initially distinguished using myofibrillar ATPase histochemistry. Subsequently, genome-wide mining identified 16 Class II myl genes, comprising eight essential and eight regulatory light-chain subunits. Their conserved-domain features, chromosomal distribution, phylogenetic relationships and expression profiles were analysed. Transcriptomic profiling showed that summed myl transcript abundance was higher in fast muscle than in slow muscle, accounting for 67.2% of the pooled myl transcript pool across the two muscle types (paired t-test, raw P = 0.036). mylpfa, myl1 and mylz3 were the major fast-muscle-associated genes, whereas myl10, myl2b and myl13 were preferentially expressed in slow muscle at the transcript level. These patterns support these genes as candidate fibre-type-associated expression markers. Developmental profiling identified stage-associated myl expression patterns, including a possible expression shift between mylpfb and mylpfa. In the descriptive injury-repair time course (d0-d7), FPKM profiles indicated that fast-muscle-associated genes (mylpfa, mylz3 and myl1) were lower at d1 and recovered by d3, whereas several slow-muscle-associated genes showed biphasic transcript-level increases. The slow-muscle-associated RLC gene mylpfb showed a delayed expression peak at d7. Notably, the embryonic isoform myl6l showed a modest increase from approximately 2 FPKM at d0 to 4-5 FPKM after injury, suggesting a possible injury-associated expression pattern that requires further validation. Together, these findings provide a genome-wide description of the Chinese perch myl gene family and identify candidate fibre-type-associated genes and descriptive injury-associated isoform expression patterns.

Animals↗