Diabetes Care最新文献

{"title":"The Association Between Hemoglobin A1c and Complications Among Individuals With Diabetes and Severe Chronic Kidney Disease","authors":"Dea H. Kofod, Nicholas Carlson, Thomas P. Almdal, Tobias Bomholt, Christian Torp-Pedersen, Kirsten Nørgaard, Jesper H. Svendsen, Bo Feldt-Rasmussen, Mads Hornum","doi":"10.2337/dc25-0339","DOIUrl":"https://doi.org/10.2337/dc25-0339","url":null,"abstract":"OBJECTIVE The optimal glycemic target for individuals with severe chronic kidney disease (CKD) remains unclear. We investigated the association between HbA1c and complications in individuals with diabetes and severe CKD. RESEARCH DESIGN AND METHODS In a Danish nationwide registry-based cohort study, we included 27,113 individuals ≥18 years old with diabetes and severe CKD (estimated glomerular filtration rate [eGFR] <30 mL/min/1.73 m2) between 2010 and 2022. As reference groups, we included an age- and sex-matched cohort of 80,131 individuals with diabetes and mild-to-moderate CKD (eGFR 30–59 mL/min/1.73 m2) and 80,797 individuals with diabetes and no-to-mild CKD (eGFR ≥60 mL/min/1.73 m2). Multiple Cox regressions were used to estimate the standardized 1-year risk of major adverse cardiovascular events (MACE), microvascular complications, and hospitalizations due to hypoglycemia across strata of HbA1c levels. RESULTS For individuals with severe CKD, the risk of MACE significantly increased at HbA1c levels ≥7.2% (55 mmol/mol) (P < 0.01) and <5.8% (40 mmol/mol) (P < 0.001), compared with an HbA1c level of 6.3–6.6% (45–49 mmol/mol). The risk of microvascular complications significantly increased at HbA1c levels ≥7.2% (55 mmol/mol) (P < 0.001), and the risk of hospitalization due to hypoglycemia significantly increased at HbA1c levels ≥6.7% (50 mmol/mol) (P < 0.001). The association patterns between HbA1c and outcomes were similar in the severe CKD cohort compared with the matched cohorts with mild-to-moderate CKD and no-to-mild CKD. CONCLUSIONS Our data suggest an HbA1c range of 6.7–7.1% (50–54 mmol/mol) to be most favorable for reducing long-term complications in this high-risk population.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"521 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144237340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk of Thyroid Tumors With GLP-1 Receptor Agonists: A Retrospective Cohort Study","authors":"Daniel R. Morales, Fan Bu, Benjamin Viernes, Scott L. DuVall, Michael E. Matheny, Katherine R. Simon, Thomas Falconer, Lauren R. Richter, Anna Ostropolets, Wallis C. Y. Lau, Kenneth K. C. Man, Shounak Chattopadhyay, Nestoras Mathioudakis, Evan Minty, Akihiko Nishimura, Feng Sun, Can Yin, Sarah L. Seager, Yi Chai, Jin J. Zhou, Yuan Lu, Carlen Reyes, Andrea Pistillo, Talita Duarte-Salles, Clair Blacketer, Martijn J. Schuemie, Patrick B. Ryan, Harlan M. Krumholz, George Hripcsak, Rohan Khera, Marc A. Suchard","doi":"10.2337/dc25-0154","DOIUrl":"https://doi.org/10.2337/dc25-0154","url":null,"abstract":"OBJECTIVE To assess the association between glucagon-like peptide 1 receptor agonist (GLP-1RA) use and risk of incident thyroid tumors. RESEARCH DESIGN AND METHODS The retrospective, active-comparator new-user cohort study used international administrative claims and electronic health record databases. Participants included patients with type 2 diabetes mellitus (T2DM) with prior metformin therapy initiating a GLP-1RA versus new users of sodium–glucose cotransporter 2 inhibitors (SGLT2is), dipeptidyl peptidase 4 inhibitors (DPP-4is), and sulfonylureas (SUs). The outcome was incident thyroid tumor and thyroid malignancy. Propensity score matching and stratification were used to adjust for confounders with an intention-to-treat and on-treatment strategy. Cox regression was used to estimate hazard ratios (HRs) pooled using a random-effects meta-analysis. Unmeasured confounding was evaluated using negative outcomes, with calibration of the HR. RESULTS A total of 460,032 users of GLP-1RAs, 717,792 users of SGLT2is, 2,055,583 users of DPP-4is, and 1,119,868 users of SUs were included. Only U.S. cohorts passed study diagnostics. Thyroid tumor incidence ranged from 0.88 to 1.03 per 1,000 person-years in GLP-1RA cohorts. GLP-1RA exposure was not associated with an increased risk of thyroid tumors compared with SGLT2is, DPP-4is, or SUs (meta-analysis: GLP-1RA vs. SGLT2i HR range from 0.83 [95% CI 0.57–1.27] to 0.95 [0.85–1.06]; GLP-1RA vs. SU HR range from 0.95 [0.75–1.20] to 1.03 [0.87–1.23]; GLP-1RA vs. DPP-4i HR range from 0.78 [0.60–1.01] to 0.93 [0.83–1.04]). Analysis using thyroid malignancy and including a 1-year lag period produced similar conclusions. CONCLUSIONS In patients with T2DM initiating second-line treatments, we observed no increased risk of thyroid tumors with GLP-1RA exposure.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"56 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144218869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of a Province-Wide Change in Gestational Diabetes Mellitus Screening Policy on Treatment and Newborn Birth Weight","authors":"Elizabeth Nethery, Jennifer A. Hutcheon, Julie Lee, Patricia A. Janssen, Laura Schummers","doi":"10.2337/dc25-0480","DOIUrl":"https://doi.org/10.2337/dc25-0480","url":null,"abstract":"OBJECTIVE To evaluate changes in gestational diabetes mellitus (GDM) treatment and newborn birth weight after a 2010 change in GDM screening recommendations from a two-step (50-g glucose challenge test + 3-h, 100-g oral glucose tolerance test [OGTT] with Carpenter-Coustan criteria) to a mix of one-step and two-step (2-h, 75-g OGTT with International Association for Diabetes in Pregnancy Study Group criteria). RESEARCH DESIGN AND METHODS We estimated effects of the screening change on the incidence of lifestyle or medication treatment, infant birth weight >90th percentile or <10th percentile for gestational age (large and small for gestational age), and endocrinologist visits using interrupted time series analysis in all 463,881 individuals with singleton pregnancies (>28 gestational weeks) from British Columbia, Canada, between 2004 and 2019. RESULTS After the screening change, lifestyle-treated GDM increased immediately (level change 1.85 [95% CI 1.19–2.51]), corresponding to a 1.85% increase in incidence. Medication-treated GDM increased gradually (trend change 0.23 [95% CI 0.09–0.37] per year), but there was no change in medication-treated GDM using a shorter (3-year) postpolicy period (level change −0.31 [95% CI −0.9 to 0.29]; trend change 0.03 [95% CI −0.36 to 0.43]). We detected no change in infant birth weight outcomes and endocrinology visits. CONCLUSIONS Changing the screening approach substantially increased diagnoses of lifestyle-treated GDM but did not impact medication-treated GDM or infant birth weight.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"11 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144218875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Overall Uptake and Racial, Ethnic, and Socioeconomic Disparities in the Use of Continuous Glucose Monitoring Devices Among Insulin-Treated Older Adults With Type 2 Diabetes","authors":"Wajd Alkabbani, Sara J. Cromer, Dae Hyun Kim, Julie M. Paik, Katsiaryna Bykov, Medha Munshi, Deborah J. Wexler, Elisabetta Patorno","doi":"10.2337/dca25-0006","DOIUrl":"https://doi.org/10.2337/dca25-0006","url":null,"abstract":"OBJECTIVE To assess time trends of and examine which sociodemographic and clinical characteristics are associated with continuous glucose monitoring (CGM) initiation in insulin-treated older adults with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS Using data from Medicare Fee-for-Service (2013–2020) and Optum’s deidentified Clinformatics Data Mart Database (Clinformatics) (2013–2022), we identified patients aged ≥65 years with T2D receiving insulin therapy who initiated CGM annually. Initiation of a CGM device was defined based on Current Procedural Terminology codes and National Drug Codes. Then, we 1:4 matched new users of CGM to patients unexposed to CGM, using risk set sampling. Index date was the date of CGM initiation or, for control participants, the closest physician visit within ±7 days. We used logistic regression to assess demographic and clinical characteristics associated with CGM initiation. RESULTS The annual CGM initiation rate rose from 107 to 5,249/100,000 in Medicare (2013–2020) and from 796 to 9,195/100,000 in Clinformatics (2013–2022). Compared with White patients, Hispanic (odds ratio, 96% CI: 0.44, 0.42–0.48 in Medicare and 0.81, 0.78–0.85 in Clinformatics) and Black (0.71, 0.69–0.73 in Medicare and 0.89, 0.85–0.92 in Clinformatics) individuals were less likely to receive CGM. Older age and residing in low socioeconomic status areas were associated with lower CGM uptake, while history of hypoglycemia and lower frailty scores increased CGM initiation likelihood. CONCLUSIONS CGM initiation has increased over time but remains <10% among insulin-treated older adults with T2D. Substantial racial, ethnic, and socioeconomic disparities were observed.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"28 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144183785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SGLT2i Versus Metformin for Delirium Prevention in Type 2 Diabetes: A Real-World, Head- to-Head Comparative Study","authors":"Mingyang Sun, Xiaoling Wang, Zhongyuan Lu, Yitian Yang, Shuang Lv, Mengrong Miao, Wan-Ming Chen, Szu-Yuan Wu, Jiaqiang Zhang","doi":"10.2337/dc25-0433","DOIUrl":"https://doi.org/10.2337/dc25-0433","url":null,"abstract":"OBJECTIVE To compare the effectiveness of sodium–glucose cotransporter 2 inhibitors (SGLT2is) versus metformin in preventing delirium among patients with type 2 diabetes (T2D), using real-world data. RESEARCH DESIGN AND METHODS We conducted a retrospective cohort study using the TriNetX global health research network, including 857,171 adults with T2D who initiated either an SGLT2i (n = 88,012) or metformin (n = 769,159) from 2005 to 2025. Propensity score matching (1:1) was used to balance covariates between groups. The primary outcome was incident delirium; secondary outcomes included all-cause mortality. Absolute risk reduction (ARR), adjusted hazard ratios (aHRs), and Kaplan-Meier survival analyses were used to assess outcomes. RESULTS After matching, SGLT2i use was associated with a significantly lower risk of delirium compared with metformin (ARR 5.03%, 3.97% vs. 9.0%; aHR 0.91 [95% CI 0.87, 0.95], P < 0.001). All-cause mortality was also lower in the SGLT2i group (ARR 9.23%, aHR 0.85 [95% CI 0.87, 0.88], P < 0.001). The most pronounced benefits were seen in adults aged ≥80 years (aHR 0.83, P < 0.0001), males, and high-risk subgroups using insulin or sedatives. CONCLUSIONS This first head-to-head, real-world study suggests that SGLT2is may offer superior protection against delirium compared with metformin in patients with T2D, especially in high-risk populations. These findings support the inclusion of cognitive outcomes in diabetes treatment decisions and suggest a potential shift in first-line therapy strategies.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"58 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144164936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"β-Cell Function Derived From Routine Clinical Measures Reports and Predicts Treatment Response to Immunotherapy in Recent-Onset Type 1 Diabetes","authors":"Michelle So, Sara Vogrin, Michaela Waibel, Thomas W.H. Kay, John M. Wentworth","doi":"10.2337/dc25-0565","DOIUrl":"https://doi.org/10.2337/dc25-0565","url":null,"abstract":"OBJECTIVE Baricitinib preserves β-cell function in people with recently diagnosed type 1 diabetes. We aimed to determine whether simple routine clinical measures could be used to assess β-cell preservation and predict treatment response. RESEARCH DESIGNS AND METHOD Measures of β-cell function derived from clinical and biochemical measures were calculated using data from the BAricitinib in Newly DIagnosed Type 1 diabetes (BANDIT) randomized trial of baricitinib in recent-onset type 1 diabetes. Measures that reported and predicted treatment efficacy were determined using linear regression and receiver operator characteristic analysis, respectively. Therapeutic predictors were validated using data from trials of rituximab, abatacept, and antithymocyte globulin. RESULTS Quantitative response score (QRS), fasting C-peptide, and model-estimated C-peptide (CPest) most reliably differentiated placebo-treated from baricitinib-treated participants at 24 and 48 weeks. The Beta2 score, derived from fasting glucose, C-peptide, HbA1c, and insulin dose at 12 weeks, was optimal for predicting QRS >0 following 1 year of treatment with baricitinib and the other immunotherapies (areas under receiver operator curve 0.864 and 0.765, respectively). A 6.2% decrease in the Beta2 score at week 12 predicted significant improvement in HbA1c (−0.6% or −6 mmol/mol) and insulin use (−0.26 units/kg/day) in combined data from the rituximab, abatacept, and antithymocyte globulin trials. CONCLUSIONS QRS, fasting C-peptide, and CPest could be used as more efficient, less burdensome primary outcome measures for future immunotherapy trials. The ability of the Beta2 score to predict treatment responses could facilitate adaptive trial designs and help guide treatment decisions in the clinic.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"98 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144153488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations of Concurrent Hypertension and Type 2 Diabetes With Mortality Outcomes: A Prospective Study of U.S. Adults","authors":"Ye Yuan, Carmen R. Isasi, Tala Al-Rousan, Arnab K. Ghosh, Pricila H. Mullachery, Priya Palta, Nour Makarem","doi":"10.2337/dca24-0118","DOIUrl":"https://doi.org/10.2337/dca24-0118","url":null,"abstract":"OBJECTIVE To investigate associations of concurrent hypertension and type 2 diabetes (T2D) with mortality in U.S. adults and elucidate differences by sex, race, and ethnicity. RESEARCH DESIGN AND METHODS The study population included 48,727 adults from the 1999–2018 National Health and Nutrition Examination Surveys. Participants were categorized into four mutually exclusive categories: 1) no hypertension and no T2D, 2) hypertension only, 3) T2D only, and 4) coexisting hypertension and T2D. Outcomes were all-cause and cardiovascular mortality defined using ICD-10 codes. Kaplan-Meier curves and multivariable Cox proportional hazards models were used to evaluate associations of hypertension and T2D status with mortality risk. RESULTS The burden of concurrent hypertension and T2D doubled between 1999 and 2018 from 6 to 12%. Overall, 50.5% of participants did not have T2D or hypertension, 38.4% had hypertension only, 2.4% had T2D only, and 8.7% had both. During a 9.2-year median follow-up, 7,734 deaths occurred. Concurrent hypertension and T2D versus no hypertension or T2D predicted higher all-cause (hazard ratio 2.46 [95% CI 2.45, 2.47]) and cardiovascular mortality risk (2.97 [2.94, 3.00]), with stronger associations in females versus males (P for interaction < 0.01). Compared with having hypertension or T2D only, concurrent hypertension and T2D predicted up to 66% and more than twofold higher all-cause and cardiovascular mortality risk, respectively, and associations varied by sex and race and ethnicity (P for interaction < 0.01), depending on the reference group (T2D only or hypertension only). Concurrent prediabetes and elevated blood pressure predicted up to 19% higher mortality risk compared with having neither or either condition. CONCLUSIONS Concurrent hypertension and T2D predict high mortality risk, underscoring the critical need for contextual interventions that extend healthspan in the U.S.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"1 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144113908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effectiveness of Low Intensity Mental Health Support via a Telehealth Enabled Network (LISTEN) for Adults With Diabetes Distress: A Parallel Group, Pragmatic Randomized Controlled Trial","authors":"Edith E. Holloway, Laura Jenkins, Paul A. Agius, Sarah Manallack, Roslyn Le Gautier, Cathrine Mihalopoulos, Mary Lou Chatterton, Vincent L. Versace, Jennifer Halliday, Virginia Hagger, Shikha Gray, Kim Henshaw, Ben Harrap, Natasha Van Bruggen, Taryn Black, Glen Noonan, Carolyn Hines, Adrienne O’Neil, Timothy C. Skinner, Jane Speight, Christel Hendrieckx","doi":"10.2337/dc24-2525","DOIUrl":"https://doi.org/10.2337/dc24-2525","url":null,"abstract":"OBJECTIVE To assess the effectiveness of Low Intensity mental health Support via a Telehealth Enabled Network (LISTEN), facilitated by diabetes health professionals, for reducing diabetes distress among adults with type 1 or type 2 diabetes. RESEARCH DESIGN AND METHODS A two-arm, parallel group, pragmatic randomized controlled trial. Adults with diabetes distress (20-item Problem Areas in Diabetes [PAID] score ≥25, or ≥2 on three or more items) were recruited via the National Diabetes Services Scheme (NDSS) and randomized (1:1) via central randomization by computer to LISTEN (maximum four sessions of problem-solving therapy) or usual care (web-based resources about diabetes and emotional health). Participants completed self-report online surveys at baseline and at 8 and 26 weeks. The primary outcome was the change in diabetes distress (PAID) from baseline to 26 weeks. Secondary outcomes included psychological distress (10-item Kessler Psychological Distress Scale), general emotional well-being (World Health Organization 5-item Well-being Index) and coping self-efficacy at 8 and 26 weeks. Data were analyzed using intention-to-treat principles. RESULTS Participants (n = 429, 59% women, 40% men, 1% nonbinary; median age 54 [interquartile range 42.0–63.5]; 37% type 1 diabetes, 63% type 2 diabetes) were enrolled and randomized to the intervention (n = 216) or control group (n = 213). Over 26 weeks, there was a greater reduction in diabetes distress among the LISTEN group versus the control group (mean difference −7.2 [95% CI −11.6, −2.8]; P < 0.001; Cohen f2 = 0.03) and greater improvements in general emotional well-being and coping self-efficacy. No adverse events were reported. CONCLUSIONS LISTEN is an effective, low-intensity program, addressing the unmet needs of adults with type 1 and type 2 diabetes experiencing mild-to-moderate diabetes distress.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"18 1","pages":"955-965"},"PeriodicalIF":16.2,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144104702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cost-effectiveness of Semaglutide Compared With Other Glucose-Lowering Medications in Treating Type 2 Diabetes: A Comprehensive Systematic Review and Meta-analysis","authors":"Ziyun Liu, Baoqi Zeng, Feng Sun, Qing Xia","doi":"10.2337/dc24-2241","DOIUrl":"https://doi.org/10.2337/dc24-2241","url":null,"abstract":"BACKGROUND Significant clinical efficacy has been shown for semaglutide in managing type 2 diabetes (T2D); however, its cost-effectiveness remains uncertain. PURPOSE To systematically review existing evidence on cost-effectiveness of semaglutide versus other T2D medications. DATA SOURCES PubMed, Embase, and the Cost-Effectiveness Analysis Registry (by 11 June 2024). STUDY SELECTION A total of 45 articles (with 119 comparisons) from 2019 onward were included, representing Europe (n = 24), North America (n = 13), and Asia (all from China) (n = 8). DATA EXTRACTION Study characteristics and model characteristics/inputs/results were extracted. Lifetime costs and quality-adjusted life-years were evaluated. Proportions for cost-effectiveness outcomes (dominant, cost-effective, not cost-effective) were calculated. Subgroup analyses by region, sponsor type, comparator type, and model assumptions were performed. In sensitivity analysis a standard willingness-to-pay threshold was applied. DATA SYNTHESIS Of the articles included, 93.3% included adoption of a lifetime horizon and 84.4% a health care perspective and 68.9% were industry sponsored. For most studies reporting quality was high (86.7%). Overall, semaglutide was dominant/cost-effective in 73.9% of all comparisons. Notably, semaglutide was found to be dominant/cost-effective in all comparisons sponsored by Novo Nordisk versus in 50.0% of these funded by nonindustry sponsors and in none funded by other industry sponsors. Additionally, semaglutide was more cost-effective in high-income countries and in studies with adoption of a broader perspective, longer horizon, and lower discount rates. Results remained consistent with conversion with a common currency unit and willingness-to-pay threshold of US$50,000. LIMITATIONS Less detailed demographic information for more granular analyses. CONCLUSIONS Semaglutide is generally cost-effective compared with other glucose-lowering medications in evaluation against within-study willingness-to-pay thresholds; however, results varied by study sponsor type, region, and model assumptions, highlighting the need for transparent and context-sensitive economic evaluations.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"129 1","pages":"1032-1041"},"PeriodicalIF":16.2,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144104696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human Physiologic Responses to Insulin in Indigenous Americans Identify a Metabolic Susceptibility Profile Linked to Diabetes","authors":"Venkatesh L. Murthy, Paolo Piaggi, Phillip Lin, Shilin Zhao, Lindsey K. Stolze, Andrew S. Perry, Robert L. Hanson, John Jeffrey Carr, James G. Terry, Leslie J. Baier, Clifton Bogardus, Clary Clish, Eric R. Gamazon, Jonathan Krakoff, Ravi V. Shah","doi":"10.2337/dc25-0151","DOIUrl":"https://doi.org/10.2337/dc25-0151","url":null,"abstract":"OBJECTIVE To identify metabolic signatures of insulin action/secretion in Indigenous Americans (IAs) and their association with diabetes. RESEARCH DESIGN AND METHODS We defined circulating metabolomic signatures of insulin action/secretion in 446 IAs, including glucose disposal rate during low-dose insulin clamp (Mlow) and endogenous glucose production (EGP) during insulin infusion (suppression of hepatic glucose production). We then determined associations of these metabolic scores with glucose tolerance (in a separate set of ∼700 IAs) and diabetes/metabolic risk in ∼2,000 individuals (from Coronary Artery Risk Development in Young Adults [CARDIA] study). We used tissue-specific gene–metabolite mapping to pinpoint genetic pathways of type 2 diabetes (T2D) implicated by metabolomic signatures. RESULTS In young IAs (mean age 29 years; mean BMI 34.9 kg/m2) without diabetes, phenotype–metabolome associations across multiple insulin action phenotypes were linked to mechanisms of fatty acid and amino acid metabolism and inflammation (among others). Metabolite-based scores of insulin action were strongly related to incident diabetes in our discovery IA population (Mlow; 49 metabolites; standardized hazard ratio [HR] 0.49; 95% CI 0.35–0.69; P < 0.0001) and also associated with measures of insulin resistance in a distinct IA population (|ρ| ∼0.3–0.5 correlation) and in the CARDIA group (median age 33 years). At ∼20 years of follow-up in CARDIA, we observed a strong BMI- and glucose-independent association of the metabolite profile of Mlow (HR 0.65; 95% CI 0.56–0.74; P < 0.0001) and EGP suppression (HR 0.66; 95% CI 0.57–0.76; P < 0.0001) with incident diabetes, directionally opposed to BMI and glucose. Genes implicated by the metabolomic signatures were strongly linked to T2D. CONCLUSIONS Metabolic signatures of clamp-determined insulin action are strongly associated with incident diabetes, suggesting causal–functional pathways of T2D.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"55 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144104708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}