Cardiovascular diabetology. Endocrinology reports最新文献

{"title":"The interplay of insulin resistance and systemic inflammation on cancer history: a nationally representative cross-sectional study from NHANES.","authors":"Xiaorui Wang","doi":"10.1186/s40842-026-00335-y","DOIUrl":"https://doi.org/10.1186/s40842-026-00335-y","url":null,"abstract":"<p><strong>Aim: </strong>To investigate whether systemic inflammation, measured by the neutrophil-to-lymphocyte ratio (NLR), modifies the cross‑sectional association between insulin resistance (IR, assessed by HOMA-IR) and overall cancer history in a nationally representative population.</p><p><strong>Methods: </strong>We conducted a cross-sectional analysis utilizing data from the 2017-2018 National Health and Nutrition Examination Survey (NHANES), which employs a complex, multistage probability sampling design. All analyses accounted for the complex survey design and sampling weights to ensure national representativeness. Weighted multivariable logistic regression was used to assess the cross‑sectional association, with an interaction term between HOMA-IR and NLR.</p><p><strong>Results: </strong>Among 3,746 adults, after adjusting for age, sex, and BMI, HOMA-IR was not independently associated with cancer history (OR = 1.00, 95% CI 0.98-1.02). The HOMA-IR × NLR interaction term was not statistically significant (P for interaction = 0.359), indicating no significant effect modification by NLR.</p><p><strong>Conclusion: </strong>In this nationally representative sample, we found no evidence that systemic inflammation, as measured by NLR, amplifies the cross‑sectional association between IR and overall cancer history. The potential synergistic effect may be confined to specific high-risk subgroups or inflammatory pathways.</p>","PeriodicalId":521069,"journal":{"name":"Cardiovascular diabetology. Endocrinology reports","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149330136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multidomain Autonomic Dysfunction assessed with COMPASS-31 among patients with type 2 diabetes in Zanzibar: prevalence and associated factors.","authors":"Hassan Thabit Haji, Ramla Muhidin Ali, Ahmed Gharib Khamis, Kaushik Ramaiya, Patricia Munseri, Fredirick L Mashili","doi":"10.1186/s40842-026-00340-1","DOIUrl":"10.1186/s40842-026-00340-1","url":null,"abstract":"<p><strong>Background: </strong>Autonomic dysfunction is an important but frequently under-recognized complication of type 2 diabetes mellitus (T2DM), particularly in settings where objective autonomic testing is not routinely available. The Composite Autonomic Symptom Score-31 (COMPASS-31) provides a practical symptom-based approach for assessing autonomic dysfunction across multiple domains. This study compared socioeconomic, lifestyle, and clinical characteristics among adults with T2DM in Zanzibar according to COMPASS-31-defined autonomic dysfunction and examined factors associated with its presence.</p><p><strong>Methods: </strong>This hospital-based cross-sectional study included 665 adults with T2DM attending the diabetes clinic at Mnazi Mmoja Hospital, Zanzibar. Autonomic symptoms were assessed using COMPASS-31, including the orthostatic intolerance, gastrointestinal, and bladder domains. Participants were classified as having autonomic dysfunction when they met the prespecified threshold for dysfunction in at least one assessed domain. Cardiovascular autonomic neuropathy (CAN) was assessed separately using standardized cardiovascular autonomic reflex tests performed with an automated CAN Analyzer and was not included in the COMPASS-31 composite outcome. Modified Poisson regression with robust variance estimation was used to calculate adjusted prevalence ratios (aPRs) and 95% confidence intervals (CIs).</p><p><strong>Results: </strong>Overall, 309 participants (46.5%) had COMPASS-31-defined autonomic dysfunction. Orthostatic intolerance was the most common domain, affecting 271 participants (40.8%), followed by gastrointestinal dysfunction in 177 (26.6%) and urinary dysfunction in 123 (18.5%). Separately, 305 participants (45.9%) met the analyzer-based criteria for CAN. In the multivariable analysis, autonomic dysfunction was more prevalent among participants without a family history of diabetes (aPR = 1.37, 95% CI: 1.16-1.61; p < 0.001), those with diabetes duration of ≥ 10 years (aPR = 1.45, 95% CI: 1.14-1.75; p < 0.001), those not using oral hypoglycemic agents (aPR = 1.66, 95% CI: 1.39-1.97; p < 0.001), and those who rarely consumed vegetables or consumed one portion per day (aPR = 1.79, 95% CI: 1.37-2.34; p < 0.001).</p><p><strong>Conclusion: </strong>Approximately half of the adults with T2DM in this tertiary-care population had COMPASS-31-defined autonomic dysfunction. Higher prevalence was associated with no family history of diabetes, longer diabetes duration, non-use of oral hypoglycemic agents, and lower vegetable intake. These findings highlight the potential value of symptom-based autonomic assessment and support further prospective research to better understand the clinical and lifestyle factors associated with autonomic dysfunction among adults with T2DM in Zanzibar.</p>","PeriodicalId":521069,"journal":{"name":"Cardiovascular diabetology. Endocrinology reports","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13685298/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149229848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiometabolic diseases in transgender populations.","authors":"Mattia Fienga, Uwe J F Tietge","doi":"10.1186/s40842-026-00336-x","DOIUrl":"10.1186/s40842-026-00336-x","url":null,"abstract":"<p><p>The number of people seeking gender-affirming medical care and gender-affirming hormone therapy (GAHT) is increasing. As sex steroids shape cardiometabolic physiology, GAHT is expected to meaningfully alter cardiometabolic risk. The aim of this review was to systematically determine and narratively synthesize evidence on the cardiometabolic effects of GAHT and identify clinically relevant knowledge gaps. We searched PubMed for English-language primary human studies published through November 26, 2025. Of 346 screened records, 96 unique original investigations were included. Most studies had less than 3 years of follow-up, the longest being 20 years in one electronic health record-based study. In transgender women, BMI was often reported as stable with higher fat and lower lean mass compared to baseline; insulin resistance tended to increase while fasting glucose and HbA1c were usually longitudinally stable. Lipid changes often showed reductions in total and low-density lipoprotein cholesterol as well as triglyceride levels. Blood pressure generally remained stable or decreased. In transgender women, VTE incidence was higher than in both cisgender women and men, whereas stroke and MI incidence was higher primarily in comparison with cisgender women. In transgender men, BMI was increased or stable and lean mass increased with variable fat mass changes and some long-term increases in visceral and liver fat. Glucose usually remained stable while insulin resistance findings were mixed. Lipid profiles commonly shifted toward lower high-density lipoprotein cholesterol and higher low-density lipoprotein cholesterol and triglycerides. Blood pressure findings were mixed with some cohorts showing an increase. In transgender men, MI incidence was higher than in cisgender women but generally not higher than in cisgender men; evidence for other cardiovascular outcomes was limited and inconsistent. Overall, evidence on systemic inflammation, renal and hepatic outcomes is sparse. In conclusion, GAHT is associated with quantifiable cardiometabolic changes, but magnitude and clinical relevance vary by regimen, population, baseline risk and study follow-up duration. Heterogeneous regimens, study methods, and confounding contribute to mixed findings. Major gaps persist with limited long-term prospective data, sparse mechanistic insights, underrepresentation of adolescents and non-European ancestry populations, and insufficient information on cardiometabolic outcomes with ageing.</p>","PeriodicalId":521069,"journal":{"name":"Cardiovascular diabetology. Endocrinology reports","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13640212/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149123880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between the cumulative average triglyceride-glucose-waist circumference index and new-onset hypertension among Chinese middle-aged and older adults-a national prospective study.","authors":"Zihao Kuang, Beien Zhang, Siyin Lin, Chao Wang, Yanming Gao, Jiaxing Zheng, Guanhua Fan","doi":"10.1186/s40842-026-00334-z","DOIUrl":"https://doi.org/10.1186/s40842-026-00334-z","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Hypertension is one of the most important chronic diseases among middle-aged and older adults in China, characterized by high prevalence, low control rates, and a substantial burden of complications. Insulin resistance (IR) is considered a key metabolic pathway in the development and progression of hypertension; however, traditional IR measurements (e.g., the hyperinsulinemic-euglycemic clamp and HOMA-IR) have limited accessibility in large community-based samples. The triglyceride-glucose index (TyG) and its combinations with adiposity/central obesity indicators (e.g., TyG-WC) have been proposed as simple surrogate markers of IR, with advantages of low cost and easy availability. Nevertheless, prospective evidence remains relatively limited regarding the relationship between the cumulative average TyG-WC-an indicator of long-term exposure-and the risk of new-onset hypertension.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This prospective cohort study used data from the China Health and Retirement Longitudinal Study (CHARLS). We first excluded participants with hypertension at baseline (2011) and then excluded those who met hypertension criteria at the second exposure assessment in 2015 or lacked hypertension information in 2020; therefore, the final analytic cohort included 2571participants aged ≥ 45 years who were hypertension-free before the 2015 TyG-WC measurement. The exposure was the cumulative average TyG-WC, calculated as the mean of TyG-WC measured in 2011 and 2015. New-onset hypertension was ascertained at the 2020 follow-up after the second exposure measurement and was defined by self-reported physician diagnosis, antihypertensive treatment status, or measured blood pressure thresholds. Multivariable Cox proportional hazards models were used as the primary association analysis, and logistic regression models were used as complementary analyses of cumulative incidence because exact calendar dates of hypertension onset were unavailable. Restricted cubic spline (RCS), subgroup and interaction, and exploratory receiver operating characteristic (ROC) curve analyses were performed.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;By the 2020 follow-up, 226 participants (8.8%) developed new-onset hypertension after the exposure window. Compared with those who remained normotensive, participants with incident hypertension were older, more likely to reside in rural areas, and had significantly higher baseline BMI, waist circumference, fasting blood glucose, systolic/diastolic blood pressure, and cumulative average TyG-WC (all P &lt; 0.05). In the fully adjusted Cox proportional hazards model, each 1-IQR increase in cumulative average TyG-WC was associated with a higher risk of hypertension (HR = 1.40, 95% CI 1.13-1.73, P = 0.002); compared with the lowest quartile (Q1), the highest quartile (Q4) had the highest risk (HR = 2.00, 95% CI 1.27-3.14, P = 0.003). Logistic regression produced directionally consistent odds estimates (per 1-IQR increa","PeriodicalId":521069,"journal":{"name":"Cardiovascular diabetology. Endocrinology reports","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13632419/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149123911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phenotypic age metrics for risk stratification of chronic disease burden and all-cause mortality in adults.","authors":"Zihao Wang, Xinru Zhong, Yuzhou Cai, Jing Wang, Baojia Lin, Longlong Liu, Shuting Li, Haimei He, Dafu Yao, Chengzhi Yan, Yutong Zou, Yi Fu, Jiaduo Sun, Qingguo Zhang","doi":"10.1186/s40842-026-00331-2","DOIUrl":"10.1186/s40842-026-00331-2","url":null,"abstract":"<p><strong>Background: </strong>Phenotypic age gap (PAG) and phenotypic age acceleration (PhenoAgeAccel) are measures of biological ageing that have been linked to adverse health outcomes. However, their relationships with common chronic diseases and mortality in nationally representative populations remain incompletely understood. We investigated the associations of PhenoAge-based ageing metrics with chronic disease burden and all-cause mortality in U.S. adults.</p><p><strong>Methods: </strong>This retrospective study included 7,624 adults from NHANES 2005-2010 and 2015-2018. Phenotypic age was calculated using chronological age and nine clinical biomarkers. PAG was defined as phenotypic age minus chronological age, and PhenoAgeAccel was derived as a binary ageing-status variable. Cross-sectional analyses examined associations between common chronic diseases and ageing metrics, while machine-learning models were used to identify key predictive factors. Longitudinal analyses evaluated associations with all-cause mortality.</p><p><strong>Results: </strong>Obesity, hypertension, arthritis, diabetes, and malignancy were among the conditions most strongly associated with accelerated biological ageing. Among the evaluated machine-learning algorithms, LightGBM showed the best predictive performance, and SHAP analyses identified obesity, hypertension, arthritis, diabetes, and malignancy as the most influential predictive features. Positive PhenoAgeAccel was associated with increased all-cause mortality(HR 5.52, 95% CI 4.26-7.15). In addition, participants with cardiometabolic multimorbidity (CMM) and positive PAG had the poorest survival outcomes, suggesting that biological-age measures may provide additional risk stratification within multimorbid populations.</p><p><strong>Conclusions: </strong>Several common chronic diseases were strongly associated with greater biological-age burden, and accelerated phenotypic ageing was linked to higher mortality risk. These findings support the potential value of PAG and PhenoAgeAccel as practical tools for risk stratification in relation to chronic disease burden and mortality.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":521069,"journal":{"name":"Cardiovascular diabetology. Endocrinology reports","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13595699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149019490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Type 1 diabetes and cardiovascular medicine.","authors":"Alicia J Jenkins, Michael Huang, Madeleine Hemphill, David Chen, Jeffrey T Ha, Yusuke Sata, Andrew Sindone, Sonali R Gnanenthiran, Nick S R Lan","doi":"10.1186/s40842-026-00338-9","DOIUrl":"10.1186/s40842-026-00338-9","url":null,"abstract":"<p><p>There are an estimated 9.5 million people living with type 1 diabetes (T1D) globally, with cardiovascular disease (CVD) remaining a major cause of morbidity and mortality despite advances in care. Atherosclerosis occurs earlier in people with T1D and those with T1D-onset in early childhood are at particularly high lifetime risk of CVD. Multiple traditional risk factors (e.g., glycaemia, lipids, blood pressure, obesity and smoking) and novel risk factors (e.g., social determinants of health, inflammation and genetics) can promote CVD in people with T1D. This highlights the need for a life-course approach to managing overall cardiovascular risk and preventing or mitigating end-stage complications such as atherosclerotic events, cardiac autonomic neuropathy and heart failure. However, most people with T1D do not meet all recommended risk factor targets. Whilst T1D-specific risk calculators for CVD are available to guide shared decision-making and risk factor management, greater awareness and further data are needed to inform their use in different T1D populations. However, there remains a relative paucity of T1D-specific clinical trial data to inform the management and therapies for CVD risk factors such as dyslipidaemia, hypertension and chronic kidney disease (CKD), and for clinically evident CVD. There is now increasing interest in the use of adjunct glucose-lowering drugs initially developed for use in type 2 diabetes, such as sodium-glucose co-transporter 2 inhibitors and glucagon-like peptide-1 agonists, and whilst some weight, glycaemia, blood pressure and albuminuria benefits have been shown, cardiovascular outcome trials (CVOT) in T1D are currently lacking. This review by a multidisciplinary team provides an overview of CVD pathophysiology, risk factor care, risk prediction and management in people with T1D.</p>","PeriodicalId":521069,"journal":{"name":"Cardiovascular diabetology. Endocrinology reports","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13591722/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149013482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Among individuals who die of COVID-19, is the percentage who had diabetes actually higher than in those dying of other viral infections?","authors":"Neha V Reddy, Virginia Pate, Til Stürmer, Rachel Wong, Jeremy Harper, Jane E Reusch, Kenneth J Wilkins, Jena Tronieri, John B Buse, Steven G Johnson, Carolyn T Bramante","doi":"10.1186/s40842-026-00325-0","DOIUrl":"10.1186/s40842-026-00325-0","url":null,"abstract":"<p><strong>Background: </strong>Early in the COVID-19 pandemic, mainstream news outlets reported that 30-40% of all coronavirus deaths in the United States occurred among individuals with diabetes. This statistic happens to reflect the approximate prevalence of diabetes in older adults, the age group at highest risk for mortality from COVID-19. To provide greater context to this statistic, we sought to quantify both the proportion of decedents from COVID-19 and from influenza who had diabetes.</p><p><strong>Methods: </strong>For assessing COVID-19 decedents who had diabetes, we used the National COVID Cohort Collaborative (N3C) data enclave, a nationally-representative, harmonized, and de-identified electronic health record database. For assessing influenza decedents who had diabetes, we used Medicare data. We restricted the N3C sample to > 65 years to align with Medicare eligibility.</p><p><strong>Results: </strong>Among older adults with inpatient mortality due to COVID-19, 46.6% (95% CI: 46.1-47.0) had diabetes. Among older adults with inpatient mortality from influenza, the crude percent with diabetes was 61.2%. When age-standardized to match the N3C COVID-19 data, the percentage of influenza decedents with diabetes was 63.1% (95% CI: 59.1-67.1).</p><p><strong>Conclusions: </strong>Among older adults with inpatient mortality from respiratory viruses, a very large proportion had diabetes before infection: 63% of influenza decedents and 47% of COVID-19 decedents. Thus, a high proportion of decedents having diabetes is not new or unique to COVID-19. These findings highlight the value of using available data to contextualize health communication to the public.</p>","PeriodicalId":521069,"journal":{"name":"Cardiovascular diabetology. Endocrinology reports","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13576349/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148972982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GLP-1 receptor agonists beyond glycemic control: integrated cardio-renal-metabolic protection across the cardiovascular kidney metabolic continuum.","authors":"Ahmed Elsayed, Wadah Jason Ayoub, Norhan Elsayed, Joshua Stephens, Ndausung Udongwo, Yousif Elsayed, Jalal K Ghali","doi":"10.1186/s40842-026-00322-3","DOIUrl":"10.1186/s40842-026-00322-3","url":null,"abstract":"<p><p>Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have undergone a fundamental repositioning, once defined by their glycemic effects, they are now established as multi-organ protective agents operating across the cardiovascular-kidney-metabolic (CKM) continuum with benefits that extend substantially beyond glucose lowering, though the precise contribution of glycemic versus non-glycemic mechanisms varies by outcome and population. Major cardiovascular and renal outcome trials; LEADER, REWIND, AMPLITUDE-O, SELECT, FLOW, and SOUL, collectively demonstrate 13-20% reductions in major adverse cardiovascular events (MACE) and meaningful attenuation of chronic kidney disease (CKD) progression in both diabetic and non-diabetic populations. Exploratory mediation analyses from SELECT suggest that a substantial fraction of cardiovascular benefit is not explained by measured cardiometabolic risk factor changes, a finding that is hypothesis-generating and informs ongoing mechanistic investigation. This narrative review synthesizes mechanistic and clinical evidence for integrated GLP-1RA CKM protection, evaluates combination strategies with Sodium-Glucose Cotransporter 2 (SGLT2) inhibitors, and confronts the implementation gap that separates extraordinary trial efficacy from modest real-world uptake, with rigorous distinction between RCT-level evidence, observational findings, and mechanistic hypotheses. We propose a CKM Disease-Modification Framework as a conceptual scaffold for clinical decision-making, rather than treating cardiovascular, renal, and metabolic risk as separate targets requiring sequential intervention. This framework positions GLP-1RAs as upstream disease-modifying agents whose early deployment across the continuum, guided by dominant comorbidity rather than glycemic status, offers the greatest opportunity for organ protection. Taken together, the evidence positions GLP-1RAs not as adjuncts to standard cardiometabolic care, but as a foundational pillar of it, one whose population-level impact is currently constrained not by biology but by cost, access, and awareness.</p>","PeriodicalId":521069,"journal":{"name":"Cardiovascular diabetology. Endocrinology reports","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13548558/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148901881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiometabolic outcomes of once-weekly IcoSema in adults with type 2 diabetes: systematic review and meta-analysis of the COMBINE trials.","authors":"Adir Alper, Adina Fagin, Aditya Karthikeyan, Mathias Lerner, Adam Gershon, Ahmed Ashraf Morgan, Gal Rubinstein, Raksheeth Agarwal, Robert Faillace","doi":"10.1186/s40842-026-00333-0","DOIUrl":"10.1186/s40842-026-00333-0","url":null,"abstract":"<p><strong>Background: </strong>Patients with type 2 diabetes face a high residual risk of atherosclerotic cardiovascular disease (ASCVD) despite advances in therapy. Once-weekly IcoSema, a fixed-ratio combination of basal insulin icodec and semaglutide, offers the potential to simultaneously address glycemic control, weight, and multiple cardiometabolic risk factors with a single weekly injection.</p><p><strong>Methods: </strong>We conducted a PRISMA-compliant systematic review and random-effects meta-analysis of randomized trials from the COMBINE program. Data from COMBINE 1 (active comparator: once-weekly insulin icodec) and COMBINE 3 (active comparator: basal-bolus insulin therapy) (N = 1,970) were pooled comparing IcoSema with insulin-based intensification strategies in patients inadequately controlled on basal insulin. COMBINE 2 was excluded because its semaglutide monotherapy comparator addresses a fundamentally different clinical question (escalation from GLP-1 RA monotherapy). The primary focus was on changes in body weight, Systolic blood pressure and HbA1c; key secondary outcomes included changes in lipid profile relevant to ASCVD risk. Certainty of evidence was assessed using GRADE.</p><p><strong>Results: </strong>IcoSema showed no statistically significant difference in HbA1c reduction compared with control (pooled MD -0.37%, 95% CI -0.95 to 0.21; P = 0.21; I²=98%) but shows highly significant body weight reduction (pooled MD -6.10 kg, 95% CI -7.21 to -5.00; P < 0.00001). It significantly lowered systolic blood pressure (MD -2.45 mmHg, 95% CI -3.52 to -1.38; P < 0.00001), total cholesterol (ETR 0.97, 95% CI 0.95-0.98; P = 0.0001), LDL-C (ETR 0.94, 95% CI 0.90-0.98; P = 0.005), triglycerides (ETR 0.94, 95% CI 0.91-0.97; P = 0.0006), and VLDL-C (ETR 0.94). An exploratory, hypothetical ASCVD risk modeling analysis based on these surrogate-marker changes is presented in the Supplementary Appendix and is intended as an illustration only.</p><p><strong>Conclusions: </strong>Once-weekly IcoSema delivers meaningful improvements in weight, blood pressure, and atherogenic lipids, all key modifiable drivers of ASCVD in adults with type 2 diabetes. These surrogate benefits, combined with reduced injection burden and low risk of hypoglycemia, suggest potential for enhanced ASCVD prevention and improved long-term adherence. Results should be interpreted as hypothesis-generating only because only two trials met the inclusion criteria. Dedicated cardiovascular outcome trials are essential to validate these surrogate-marker benefits and to confirm whether they translate into a reduction in cardiovascular events.</p>","PeriodicalId":521069,"journal":{"name":"Cardiovascular diabetology. Endocrinology reports","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13536828/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148877145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Which heart failure phenotypes benefit from GLP-1 receptor agonists?","authors":"Jianxin Deng","doi":"10.1186/s40842-026-00328-x","DOIUrl":"10.1186/s40842-026-00328-x","url":null,"abstract":"<p><p>GLP‑1 receptor agonists reduce heart failure hospitalization in pooled analyses, but whether this benefit applies across the spectrum of heart failure phenotypes remains unclear. This correspondence highlights that dedicated trials showing efficacy in obesity‑associated HFpEF enrolled highly selected populations, whereas the included cardiovascular outcome trials lacked detailed heart failure phenotyping. Evidence for GLP‑1RAs in HFrEF is limited. We call for standardized heart failure phenotyping and phenotype‑specific analyses to clarify whether the observed benefit is a class effect or preferentially confined to metabolically defined subgroups.</p>","PeriodicalId":521069,"journal":{"name":"Cardiovascular diabetology. Endocrinology reports","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13527946/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148868478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}