Diabetes, Obesity & Metabolism最新文献

Continuous glucose monitoring (CGM) is now central to diabetes management, yet variation in how respective medical products are evaluated limits meaningful comparison between CGM systems. Three barriers currently constrain reliable interpretation of glucose-derived measures. The first is limited transparency: in several regulatory settings, particularly those using Conformité Européenne marking, clinical-study reports, reference-method information and analytical documentation required for market authorisation are not publicly accessible. The second barrier is heterogeneity in study procedures. Existing evaluations use different reference-glucose methods, sampling strategies, glucose-manipulation protocols and participant characteristics, leading to accuracy estimates that cannot be interpreted consistently across systems. The third barrier is calibration alignment. Even with full transparency and aligned procedures, CGM systems may differ because their calibration algorithms are trained on distinct reference-glucose datasets, influencing reported glucose ranges, automated insulin-delivery behaviour and interpretation during device transitions. A modified Delphi process involving clinicians, laboratory scientists, and researchers identified these issues as the principal determinants of comparability. During this process, the International Federation of Clinical Chemistry and Laboratory Medicine released a validated framework for performance evaluation of CGM systems, providing a unified approach to reference-method selection, dynamic in-clinic testing, and structured reporting. Adoption would reduce procedural variability but does not resolve calibration-alignment differences. This international clinical opinion proposes a pathway towards internationally interpretable CGM evaluation: immediate transparency of clinical evidence, routine declaration of calibration alignment, and progressive adoption of validated standardised procedures. These steps provide a foundation for reliable interpretation and globally comparable assessment of CGM technologies.

Introduction: With new advancements in obesity medicine, clarity on goals and expectations for successful disease management is limited. This post hoc analysis assessed application of proposed treat-to-target (TtT) thresholds for obesity to the outcome measures of SURMOUNT-5, which randomised participants with obesity to tirzepatide or semaglutide.

Methods: The proportion of participants in each treatment group reaching proposed TtT thresholds for waist to height ratio (WHtR) <0.53, body mass index (BMI) <27 kg/m², or a combination was evaluated. The associations between the thresholds and achieving low disease activity to remission (meeting goals for at least four of five defined cardiometabolic risk parameters) and normalisation or improvement in SF-36v2 physical component score (PCS) from baseline to week 72 were explored.

Results: About 23.1%-33.9% of participants treated with tirzepatide and 14.2%-20.7% treated with semaglutide reached the TtT thresholds, with greater weight reduction than the overall population. About 77% of participants who reached WHtR <0.53 achieved low disease activity to remission, with an odds ratio of 2.31 (p < 0.001) compared to those who did not reach this target. The BMI threshold was not statistically associated with the assessed outcomes for SF-36v2 PCS.

Conclusion: In this post hoc analysis of SURMOUNT-5, most participants who reached the proposed TtT thresholds achieved the goal of low disease activity to remission defined by cardiometabolic risk parameters. These data suggest that TtT thresholds in obesity medicine may clarify goals in shared decision-making and improve clinical outcomes.

Aim: Coronary artery calcium (CAC) scoring is observed to improve risk stratification for major adverse cardiovascular events (MACE). Semaglutide, a recently introduced anti-obesity drug, is very effective, but wider use is limited due to high costs. Hence, this study investigated the cost-effectiveness (CEA) of semaglutide across CAC groups.

Materials and methods: CAC scores for 38 058 CLARIFY registry participants meeting SELECT criteria were included. They were stratified into four CAC groups: 0, 1-99, 100-399, ≥400. To determine MACE (composite of myocardial infarction, heart failure, stroke or all-cause mortality) risk across CAC groups, hazard ratios (HR) were estimated from multi-variable adjusted Cox proportional hazard models. Next, lifetime-horizon Markov models were created to simulate semaglutide therapy and the potential clinical benefit (reported as number needed to treat [NNT]) and CEA (estimated with incremental cost-effectiveness ratio [ICER]) were examined for CAC groups. Multiple scenarios to mimic real-world experience were fitted for robust sensitivity analyses.

Results: Compared to CAC = 0, MACE risk was higher for CAC ≥400 (HR: 1.97 [95% CI: 1.66-2.35]), heart failure (HR: 1.76 [95% CI: 1.36-2.28]), mortality (HR: 1.62 [95% CI: 1.21-2.17]). Modelling 3.3 years of semaglutide use resulted in potential MACE NNT values of 151 (95% CI: 108-302) and 34 (95% CI: 25-69) for CAC = 0 and CAC ≥400. Markov modelled ICER for semaglutide use reduced across CAC groups ($625 863/QALY [CAC = 0] vs. $168 666/QALY [CAC ≥400]).

Conclusions: CAC scores have potential use as a tool to estimate potential clinical benefit and cost for lifetime semaglutide therapy among obese individuals.

Aims: To assess characteristics associated with earlier (≤2 years since diagnosis) versus later (>2 years) insulin pump initiation among new type 1 diabetes applicants to the publicly funded insulin pump program in Ontario, and whether timing of pump initiation is associated with cumulative glycaemic exposure.

Materials and methods: A retrospective population-based cohort study was conducted using administrative healthcare databases in Ontario, Canada. All pump program applicants prior to 31 March 2021 were included. An adjusted log-binomial regression model using generalized estimating equations assessed associations between patient- and physician-level characteristics and earlier versus later pump initiation. A linear regression model examined differences in cumulative HbA1c over time between earlier versus later pump initiators.

Results: Among 4899 individuals, 62.6% were earlier pump initiators. Greater social disadvantage was associated with lower likelihood of earlier pump initiation [adjusted relative risk (RR) 0.81 (95% confidence interval {CI} 0.75-0.88)] for most versus least disadvantaged quintile. Compared to paediatrician care, endocrinologist [RR 0.85 (95% CI 0.79, 0.91)], general internist [0.73 (0.64-0.83)], and family physician care [0.28 (0.21-0.37)] were associated with less earlier pump initiation. Older age at diagnosis and physician training prior to publicly funded pump therapy were associated with less earlier pump initiation. Earlier pump initiators had a significantly lower annual rate of increase in cumulative HbA1c compared with later initiators (-0.33% per year; 95% CI -0.45 to -0.20; p < 0.001), although cumulative HbA1c at 10 years did not differ significantly between groups (mean difference -1.50; p = 0.112).

Conclusions: Social disadvantage and physician characteristics are associated with less earlier pump initiation, which may have negative long-term effects on glycaemic management. Barriers to earlier pump initiation should be removed to promote equitable access and optimize glycaemic outcomes.

Aims: Prognostic markers for microvascular complications in type 1 diabetes are needed because factors beyond hyperglycaemia contribute to this risk. The triglyceride-glucose (TyG) index is an established marker of vascular complications in type 2 diabetes; however, its clinical significance in type 1 diabetes remains unknown. We aimed to investigate the association between the TyG index and long-term renal outcomes in a nationwide cohort of adults with type 1 diabetes.

Materials and methods: In this nationwide cohort study of 14 782 adults with type 1 diabetes from the Korean National Health Insurance Service database, we used Cox proportional hazards models to evaluate the risk of incident chronic kidney disease (CKD) and end-stage renal disease (ESRD) across quartiles of the baseline TyG index during a median follow-up of 7.04 years.

Results: A significant dose-response relationship was observed between the TyG index and adverse renal outcomes. After multivariable adjustment, the highest TyG quartile (Q4) had a 2.15-fold (95% confidence interval, 1.87-2.48) and a 2.90-fold (95% confidence interval, 2.25-3.75) higher risk of developing CKD and ESRD, respectively, than the lowest quartile (Q1) (p for trend <0.001 for both). These associations remained significant in a competing-risk analysis that included all-cause mortality. Additionally, higher TyG quartiles were associated with a progressively worsening distribution of 5-year CKD stages.

Conclusions: The TyG index may serve as a valuable clinical indicator to identify individuals with type 1 diabetes at high risk for developing incident CKD and ESRD.

Aims: Magnetic resonance imaging (MRI) provides the most accurate assessments of site-specific fat accumulation, but is not readily available. Less-accurate methods, such as Dual-energy x-ray absorptiometry (DXA), bioelectrical impedance analysis (BIA), and anthropometry, have been widely used to measure overall and regional adiposity. However, the extent to which these approaches reflect MRI-derived fat depots is not fully understood.

Materials and methods: We included 18 622 White participants from the UK Biobank imaging visit. A total of 27 indices from DXA, BIA, and anthropometry were selected to characterise overall and regional adiposity, and all indices were standardised. In subgroups stratified by age and sex, Pearson correlation coefficients were used to assess the degree of linear association between these indices and MRI-determined subcutaneous, visceral, liver, and pancreas fat. Intraclass correlation coefficients (ICC) were further calculated to evaluate the absolute agreement between the corresponding fat measures.

Results: Generally, correlations of adiposity indices from DXA (total, trunk, android, gynoid, arm, and leg fat), BIA (total, trunk, arm, and leg fat), and anthropometry (body mass index (BMI), waist and hip circumference) with MRI measures were strongest for subcutaneous fat, followed by visceral fat, and weakest for liver and pancreas fat. The correlation coefficients with MRI-based visceral fat were larger for indices reflecting abdominal adiposity (e.g., DXA-based visceral, android, and trunk fat, BIA-based trunk fat, and waist circumference) and for measures of total adiposity (e.g., DXA- and BIA-derived total fat). The absolute agreement with MRI-based visceral fat was highest for DXA-based visceral, trunk, and android fat (ICC = 0.73-0.94), followed by waist circumference (ICC = 0.73-0.77), and then the remaining indices.

Conclusions: Indices of abdominal adiposity (as indicated by DXA-derived visceral, trunk, and android fat and waist circumference) appeared highly reflective of MRI-determined visceral fat. Considering cost and accessibility, waist circumference may serve as the most appropriate surrogate for assessing visceral fat.

Aims: Mixed evidence exists on whether metformin adds to or attenuates the insulin-sensitising effects of exercise. To date, no studies have tested whether metformin differentially impacts exercise training intensity-mediated insulin sensitivity. We tested the hypothesis that metformin would blunt metabolic insulin sensitivity and carbohydrate oxidation in an intensity-based manner among adults with metabolic syndrome (MetS) risk.

Materials and methods: In a double-blind, placebo-controlled trial, participants were randomised to low-intensity exercise plus placebo (~55% VO₂max 5 days/week, LoEx + PL, n = 22) or metformin (2000 mg/day, LoEx + Met, n = 21) and high-intensity exercise plus placebo (~85% VO₂max 5 days/week, HiEx + PL, n = 24) or metformin (HiEx + Met, n = 24) for 16 weeks. A 120-min euglycaemic-hyperinsulinemic clamp (40 mU/m²/min, 90 mg/dL) was conducted pre- and post-treatment to assess metabolic insulin sensitivity (M-value/insulin). Fasting and insulin-stimulated carbohydrate oxidation was also assessed using indirect calorimetry. Adipokines (leptin, high molecular weight (HWM), and total adiponectin) were measured at 0 and 120 min of the clamp. Aerobic fitness (VO₂max) and body composition (DXA) were also analysed.

Results: HiEx + PL increased metabolic insulin sensitivity (p = 0.017) while HiEx + Met, LoEx + PL, or LoEx + Met did not. HiEx + PL also raised insulin-stimulated carbohydrate oxidation and decreased fat oxidation compared with LoEx + Met (both, p = 0.008). Increased metabolic insulin sensitivity related to reductions in fasting glucose (r = -0.41, p = 0.025), VO₂max (r = 0.55, p = 0.002), fasting leptin (r = -0.54, p = 0.01), and weight loss (r = -0.60, p < 0.001) after exercise and placebo, but not exercise and metformin.

Conclusions: Metformin attenuated metabolic insulin sensitivity and insulin-stimulated carbohydrate oxidation after high-intensity exercise training in adults at risk for MetS.

Aim: Heart failure with preserved ejection fraction (HFpEF) presents a therapeutic challenge, characterised by a paucity of validated treatments. Emerging data suggest that targeting adiposity is central to HFpEF pathogenesis. We conducted an updated network meta-analysis to compare the efficacy of emerging and established HFpEF therapies.

Materials and methods: We systematically searched PubMed, Embase and Cochrane Library from inception to April 2025 for randomised controlled trials enrolling patients with HFpEF and evaluating pharmacotherapies, including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta blockers, mineralocorticoid receptor antagonists (MRAs), digoxin, angiotensin receptor-neprilysin inhibitor, sodium-glucose transporter 2 inhibitors (SGLT2is), glucagon-like peptide-1 receptor agonists (GLP-1 RAs), nitrates and nitrites. The primary outcome was a composite of cardiovascular death and heart failure (HF) hospitalisation. The secondary outcomes included cardiovascular death, all-cause mortality, worsening HF events, change in the 6-min walk test (6MWT) distance, Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) and N-terminal pro-B-type natriuretic peptide levels. A frequentist random-effects NMA was conducted.

Results: Thirty-nine trials with 78 treatment arms and 48 235 patients were enrolled. Compared with placebo, GLP-1 RAs (HR: 0.73, 95% CI 0.61-0.88) and SGLT2is (HR: 0.79, 95% CI 0.70-0.90; P-score: 0.807) significantly reduced the risk of cardiovascular death and HF hospitalisation. GLP-1 RAs showed the highest probability of ranking first (P-score: 0.871). GLP-1 RAs elicited the greatest improvement in functional outcomes, including the 6MWT (mean difference: +17.60 m, 95% CI 8.53-26.67) and KCCQ-CSS (mean difference: +7.38 points, 95% CI 5.51-9.26). No statistically significant differences in cardiovascular death or all-cause mortality were observed among the treatments.

Conclusions: In patients with HFpEF, GLP-1RA, SGLT2i and MRA significantly reduced the risk of cardiovascular death and HF hospitalisation, while GLP-1RA additionally improved the functional and quality-of-life outcomes. GLP-1RA and SGLT2i significantly reduced HF morbidity, and GLP-1RA uniquely improved functional status, positioning adiposity modulation as a central therapeutic target in HFpEF.

Aims: Real-world medication use varies across clinical trial and healthcare settings; therefore, we evaluated GLP-1 receptor agonist (GLP-1RA) persistence and dose titration among adults with type 2 diabetes in UK primary care, stratified by agent, obesity status, cardiovascular disease (CVD) history, and sex assigned at birth.

Materials and methods: Adults with type 2 diabetes initiating GLP-1RAs between 1 March 2018 and 30 June 2023, with follow-up ≥1-year, were identified using the IQVIA Medical Research Data (IMRD) incorporating data from THIN, A Cegedim Database. The absolute 1-year risk of discontinuation was estimated using the Aalen-Johansen estimator, while multivariable cause-specific Cox models assessed associations with patient characteristics. Dosing trajectories were characterised across individual prescriptions during the first therapy year.

Results: Among 8200 GLP-1RA initiators (46.5% dulaglutide, 38.7% semaglutide), the 1-year discontinuation risk was 41.1% (95% CI 40.1-42.2), higher among those without obesity (BMI <30 kg/m²: 49.2%, 46.5-52.0) versus with BMI ≥30 kg/m² (BMI 30-<35/≥35 kg/m²: 40.4%/37.2%, 38.4-42.4/35.4-39.1). Discontinuation was lower with dulaglutide (36.9%, 35.4-38.4) than with subcutaneous/oral semaglutide (46.4%/55.8%, 44.4-48.4/52.3-59.4). Only 58% of subcutaneous/oral semaglutide initiators reached recommended maintenance doses after 4 weeks, while 21% remained on starting doses. At prescription 10, most common doses were 0.5/1 mg subcutaneous semaglutide (44.0%/48.6%), 7/14 mg oral semaglutide (50.2%/36.6%), and 0.75/1.5/3 mg dulaglutide (20.4%/71.5%/6.7%). Faster dose escalation occurred with higher BMI and subcutaneous semaglutide (1 mg at prescription 5: 20.8%/25.9%/33.2% with BMI <30/30-<35/≥35 kg/m²). Additional analyses (e.g., by CVD history) revealed no further heterogeneity.

Conclusions: In UK primary care, GLP-1RA persistence was suboptimal and dose escalation was frequently delayed across all patient stratifications, including individuals with established CVD.

Aims: To evaluate the cardiovascular efficacy of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in Asian, Black or African American, and White populations, and to assess whether the magnitude of cardiovascular risk reduction differs across these populations.

Materials and methods: PubMed and EMBASE were searched to 11 November 2025 for randomized placebo-controlled GLP-1RA trials in adults with type 2 diabetes or overweight/obesity that reported race-stratified major adverse cardiovascular events (MACE; cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke). Hazard ratios (HRs) for MACE were extracted for Asian, Black or African American, and White populations. Random-effects meta-analyses were used to obtain pooled HRs and ratios of HRs (RHRs) comparing treatment effects between populations.

Results: Nine trials, including the recent SOUL trial, were included, comprising 8164 Asian, 4036 Black or African American, and 62 503 White participants. GLP-1RAs reduced MACE risk in Asian (HR 0.73; 95% CI 0.63-0.85; p < 0.001) and White populations (HR 0.86; 95% CI 0.81-0.91; p < 0.001). In Black or African American populations, the effect was similar to that in White populations (HR 0.88; 95% CI 0.67-1.15; p = 0.34) but did not reach statistical significance. The pooled RHR for Asian versus White populations was 0.84 (95% CI 0.71-0.98; p = 0.027), indicating a significantly greater risk reduction in Asian populations. The RHR for Asian versus Black or African American populations was 0.81 (95% CI 0.57-1.16; p = 0.25), with point estimates favouring Asian populations.

Conclusions: GLP-1RAs reduced MACE risk across populations, with greater relative risk reduction in Asian populations and broadly similar benefits in Black or African American and White populations.