Wiley最新文献

{"title":"Rewiring the TaGSK3-TaGW2-Rht1 Module for Ideotype Wheat Varieties.","authors":"Yufan Wang, Yunwei Zhang, Shuxian Huang, Jiatong Qiu, Guozhong Sun, Jiaqiang Sun","doi":"10.1111/pce.70849","DOIUrl":"10.1111/pce.70849","url":null,"abstract":"","PeriodicalId":222,"journal":{"name":"Plant, Cell & Environment","volume":" ","pages":"9711-9714"},"PeriodicalIF":6.9,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148862833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The OsSRLD-OsIMα1a-OsWRKY53 and OsSRLD-OsDIP1 Modules Balance Disease Resistance and Drought/Salt Tolerance in Rice.","authors":"Yapu Cheng, Kexing Fang, Tiancheng Qiu, Qingyuan Bai, Yayan Feng, Qingya Yang, Jun Yang, Xujun Chen, Vijai Bhadauria, You-Liang Peng, Wensheng Zhao","doi":"10.1111/pce.70856","DOIUrl":"10.1111/pce.70856","url":null,"abstract":"<p><p>Understanding the molecular mechanisms underlying plant responses to various stresses is crucial for improving crop productivity under stressful conditions. However, how plants prioritize the activation of pathways to balance disease resistance with drought and salt tolerance remains unclear. Here, we identify two regulatory modules centered on the rice protein OsSRLD, which negatively regulates disease resistance and positively regulates drought/salt tolerance. Upregulation of OsSRLD increases ABA content and reduces ROS levels under both normal and stressed conditions, suggesting its involvement in ABA signaling and ROS homeostasis. As an E3 ligase, OsSRLD interacts with OsIMα1a (a positive regulator of disease resistance) and promotes its ubiquitination and degradation via the 26S proteasome. Additionally, OsIMα1a interacts with OsWRKY53 (a positive regulator of disease resistance but a negative regulator of salt tolerance), thereby promoting the nuclear accumulation of OsWRKY53. Consistently, both overexpression of OsSRLD and knockout of OsIMα1a resulted in downregulation of OsWRKY53-activated genes and upregulation of OsWRKY53-inactivated genes. Furthermore, OsSRLD interacts with and stabilizes OsDIP1 (a positive regulator of drought and salt tolerance) via an E3 ligase-independent pathway. Together, our findings reveal that OsSRLD-OsIMα1a-OsWRKY53 and OsSRLD-OsDIP1 modules balance disease resistance and drought/salt tolerance through both E3 ligase-dependent and E3 ligase-independent pathways.</p>","PeriodicalId":222,"journal":{"name":"Plant, Cell & Environment","volume":" ","pages":"9788-9807"},"PeriodicalIF":6.9,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148862940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of GLP-1 Receptor Agonists Versus Other Antidiabetic Medications With Cardiovascular, Renal, and Liver Outcomes in Patients With Type 2 Diabetes.","authors":"Yuqing Fan, Nan Peng, Linfeng Jiang, Ruolan Wei, Guoxian Lu, Shuo Zhang, Chen Mu, Mengyao Xue, Beini Lyu, Dongning Yao","doi":"10.1111/dom.71313","DOIUrl":"10.1111/dom.71313","url":null,"abstract":"<p><strong>Aims: </strong>To compare cardiovascular, kidney, and liver outcomes of Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) versus seven other antidiabetic medications (ADMs) in Chinese patients with Type 2 diabetes.</p><p><strong>Materials and methods: </strong>This retrospective cohort study (2018-2024) used an Eastern China regional healthcare database. We included patients initiating GLP-1 RAs, sodium-glucose cotransporter-2 inhibitors (SGLT-2 inhibitors), dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors), insulins, sulfonylureas, α-glucosidase inhibitors (AGIs), thiazolidinediones, or meglitinides. Outcomes were major adverse cardiovascular (MACE), kidney (MAKE), and liver (MALO) events. A propensity score-based matching weights (MWs) approach was used to balance covariates including demographics, comorbidities, and medication use, and Cox proportional hazards models were conducted in both intention-to-treat and per-protocol analyses.</p><p><strong>Results: </strong>Among 105 391 patients, SGLT-2 inhibitors (HR 1.19, 95% CI 1.10-1.30), insulins (HR 1.42, 95% CI 1.32-1.52), sulfonylureas (HR 1.30, 95% CI 1.18-1.43), and AGIs (HR 1.45, 95% CI 1.31-1.59) were associated with higher MACE risk compared with GLP-1 RAs. DPP-4 inhibitors (HR 3.09, 95% CI 1.69-5.63), insulins (HR 6.11, 95% CI 4.37-8.54), and meglitinides (HR 4.56, 95% CI 2.32-8.97) were associated with higher MAKE risk. Higher MALO risk was observed with DPP-4 inhibitors (HR 1.48, 95% CI 1.21-1.79), insulins (HR 2.06, 95% CI 1.81-2.34), AGIs (HR 1.55, 95% CI 1.26-1.90), and meglitinides (HR 1.43, 95% CI 1.07-1.92).</p><p><strong>Conclusions: </strong>GLP-1 RAs were associated with favourable cardio-renal-metabolic outcomes compared with several second-line glucose-lowering agents, particularly insulins and sulfonylureas. These findings add to the real-world evidence supporting the potential cardiovascular, renal, and hepatic benefits of GLP-1 RAs in patients with T2DM.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":"11194-11205"},"PeriodicalIF":6.1,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148910307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative Multi-Omics Analysis of Stem Growth Habit Divergence in Wild Soybean (Glycine soja).","authors":"Xiulin Liu, Xueyang Wang, Huilong Hong, Kenzhen Zhao, Chunlei Zhang, Fengyi Zhang, Rongqiang Yuan, Dai Shi, Sobhi F Lamlom, Bixian Zhang, Honglei Ren","doi":"10.1111/pce.70872","DOIUrl":"10.1111/pce.70872","url":null,"abstract":"<p><p>Stem architecture is a major determinant of lodging resistance, biomass accumulation, and harvest efficiency in soybean. However, the molecular features associated with contrasting stem growth habits in wild soybean remain incompletely characterised. Here, we performed an integrated transcriptomic, metabolomic, and epigenomic analysis of stem growth-habit divergence in wild soybean, comparing the wild-type accession ZYD7068 with contrasting vining and erect mutant lines derived from carbon-ion beam mutagenesis. Pairwise transcriptomic comparisons identified between 20 311 and 28 705 differentially expressed genes per contrast, with a core set of 2672 genes consistently altered across the comparisons. Functional enrichment, gene set variation analysis, and gene set enrichment analysis converged on xylem and phloem pattern formation as a prominent molecular pathway associated with growth-habit divergence. Random forest analysis identified BBR-BPC and ARF transcription factor families as major molecular discriminators, while metabolomic profiling revealed distinct metabolic profiles involving amino-acid-derived and lipid-associated metabolites. Whole-genome bisulfite sequencing revealed context-specific DNA methylation differences, including substantial variation in CHG methylation among erect mutant lines. Integrated network and in silico perturbation analyses prioritised four candidate genes associated with vascular development for future functional validation. Together, these results provide a multi-layer molecular resource for investigating stem growth-habit divergence in G. soja and establish testable candidate pathways and genes for subsequent functional studies and soybean improvement.</p>","PeriodicalId":222,"journal":{"name":"Plant, Cell & Environment","volume":" ","pages":"10064-10080"},"PeriodicalIF":6.9,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148917609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fracture-Centred Skeletal Reporting Profiles of Glucose-Lowering Drug Classes in FAERS and JADER: Cross-Database and Regional Reporting-Context Analyses.","authors":"Bin Huang, Panpan Ma, Wei Wang","doi":"10.1111/dom.71319","DOIUrl":"10.1111/dom.71319","url":null,"abstract":"<p><strong>Aims: </strong>To characterise fracture-centred skeletal adverse-event reporting across nine glucose-lowering drug classes and test whether regional differences persist after separating Japan from non-Japan Asian reporting contexts.</p><p><strong>Materials and methods: </strong>We analysed FAERS and JADER reports, with fracture as the primary endpoint and reporting frequency per 10 000 mapped suspect reports. FAERS older age was harmonised to ≥ 60 years, with ≥ 65 and ≥ 70-year sensitivity analyses. Regional analyses separated Western, Japan, and non-Japan Asia; class-specific reporting odds were adjusted for age, sex, calendar year, and reporter type. Disproportionality analyses were supplementary.</p><p><strong>Results: </strong>The study included 15 473 015 FAERS and 1 037 161 JADER reports, including 202 881 and 10 678 fractures. Using final deduplicated FAERS denominators, fracture reporting was highest for insulin (126.08/10000), DPP-4 inhibitors (111.03) and sulfonylureas (103.76), whereas thiazolidinediones (152.54), SGLT2 inhibitors (115.14) and GLP-1 receptor agonists (112.15) were most prominent in JADER. Age was unavailable in 44.9% of unique FAERS suspect reports, but findings were stable across age thresholds. Japan accounted for 83.0%-92.9% of total-Asian fractures for thiazolidinediones, GLP-1 receptor agonists, SGLT2 inhibitors and DPP-4 inhibitors; corresponding non-Japan Asian RFRs were not clearly elevated. Insulin remained higher after excluding Japan (RFR 1.96, 95% CI 1.57-2.45). No class met FDR-positive fracture disproportionality criteria.</p><p><strong>Conclusions: </strong>Skeletal reporting profiles varied by drug class, database, and reporting context. Apparent total-Asian elevations for several classes were predominantly Japan-driven and should not be interpreted as patient-level Asian fracture risk.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":"11310-11319"},"PeriodicalIF":6.1,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148962855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heat Shock Factor TaHSFA6e Interacts With TaNAC019 to Activate TaHSP70 Expression and Positively Contributes to Salt Stress in Wheat.","authors":"Weiwei Guo, Zubaidai Abudukerimu, Junrong Li, Luhua Wang, Xueqing Shi, Junwei Xin, Jiafei Yu, Shengjing Chen, Nan Niu, Yuxin Xie, Mingming Xin, Huifang Wang, Ximei Li, Nataliia Golub, Yumei Zhang","doi":"10.1111/pce.70898","DOIUrl":"10.1111/pce.70898","url":null,"abstract":"<p><p>Soil salinization, exacerbated by seawater intrusion and climate change, poses a major constraint on crop production. To cope with salt stress, plants have evolved complex mechanisms involving numerous tolerance-related genes. We identified that heat shock protein TaHSP70 acted as a positive regulator in response to salt stress in wheat. Further analysis revealed that heat shock transcription factor TaHSFA6e and NAC transcription factor TaNAC019 physically interact and function additively to activate TaHSP70 expression. Whereas a single-nucleotide T insertion within the coding sequence of TaNAC019-B reduced the transcriptional activity of TaHSP70. Overexpression of either TaHSFA6e or TaNAC019 enhanced salt tolerance in wheat. Collectively, these findings highlight the importance of the heat shock protein pathway in mediating salt stress responses in wheat.</p>","PeriodicalId":222,"journal":{"name":"Plant, Cell & Environment","volume":" ","pages":"10475-10489"},"PeriodicalIF":6.9,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149023551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aphid Probing and Phloem Feeding Trigger Distinct Plant Immune Programs, Identifying a Broad‑Spectrum Trypsin Protease Inhibitor.","authors":"Zeyu Wan, Xinting Qiu, Xichen Xiao, Hanwei Kang, Yongmo Wang","doi":"10.1111/pce.70916","DOIUrl":"10.1111/pce.70916","url":null,"abstract":"<p><p>Aphid feeding begins with brief exploratory probing and transitions to prolonged phloem ingestion, yet whether these distinct phases trigger different plant immune programs remains unknown. We show that probing and phloem feeding are associated with distinct plant immune cascades. Under probing-enriched conditions, we observed selective activation of jasmonate (JA) signaling, accompanied by significant ROS bursts and vascular callose deposition, whereas phloem feeding elicits only marginal salicylic acid accumulation. Probing-enriched conditions imposes severe fitness penalties on aphids, a phenotype recapitulated by exogenous methyl jasmonate. Consistent with this, aphids exhibit high feeding‑site fidelity, which likely minimizes probing events and helps evade these penalties. Transcriptome analysis identified the squash‑type trypsin protease inhibitor CsTrypPI1, characterized by six conserved cysteines, as a JA-dependent component upregulated under probing-enriched conditions. Recombinant CsTrypPI1 directly impairs aphid survival and fecundity in artificial diet assays. Transgenic cucumber lines constitutively over‑expressing CsTrypPI1 displayed broad‑spectrum resistance against the aphid Aphis gossypii, the whitefly Bemisia tabaci, and the lepidopteran Spodoptera litura. Our findings indicate that the probing versus phloem feeding comparison defines two distinct immunological trajectories, which helps reconcile conflicting evidence on JA and SA roles in plant and phloem‑feeder interactions. The identification of CsTrypPI1 as a broad‑spectrum resistance candidate highlights this behavioral-immunological interface as a promising intervention point for sustainable pest management.</p>","PeriodicalId":222,"journal":{"name":"Plant, Cell & Environment","volume":" ","pages":"10459-10474"},"PeriodicalIF":6.9,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149023564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LncRNA MtCIR2 Negatively Regulates Response of Medicago truncatula Seedlings to Salt Stress by Targeting SOS2-Dependent Na Efflux via H2A Ubiquitination.","authors":"Xiaohan Sun, Rui Tian, Mingui Zhao, Wen-Hao Zhang","doi":"10.1111/pce.70904","DOIUrl":"10.1111/pce.70904","url":null,"abstract":"<p><p>Increasing evidence indicates that long non-coding RNAs (lncRNAs) play a regulatory role in plant responses to environmental stress. However, the epigenetic mechanisms behind the regulation of salt stress by lncRNAs remain largely elusive. We previously discovered that the lncRNA MtCIR2 of Medicago trnucatula negatively regulated seed germination under salt stress by altering endogenous ABA and GA concentrations via histone ubiquitination. Here we evaluated the roles of MtCIR2 in regulating response of M. truncatula seedlings to salt stress. We found that over-expression and mutation of MtCIR2 reduced and enhanced tolerance to salt stress due to enhanced and suppressed foliar Na accumulation in over-expression and Mtcir2 mutant plants relative to their wild-type counterparts under salt stress. The MtCIR2-depenent Na accumulation was accounted for by the suppression of MtSOS2 that encodes a kinase responsible for Na exclusion from plants. We discovered that MtCIR2 physically interacted with BMI1, a core component of Polycomb Repressive Complex 1 (PRC1), leading to down-regulation of MtSOS2. ChIP assays revealed that MtCIR2 facilitated H2A ubiquitination at the chromatin of MtSOS2, thus repressing its expression, which in turn suppressed the SOS-dependent Na exclusion, and rendered the plants sensitive to salt stress. These results unravel a novel mechanism by which lncRNA epigenetically regulates SOS-mediated Na accumulation via histone ubiquitination in plant response to salt stress.</p>","PeriodicalId":222,"journal":{"name":"Plant, Cell & Environment","volume":" ","pages":"10548-10557"},"PeriodicalIF":6.9,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149029321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multilevel Mechanisms by Which Membrane Transport Proteins Regulate Plant Responses to Heavy Metal Stress: From Ion Perception and Uptake Control to Systemic Signaling and Translational Perspectives.","authors":"Liuliu Wu, Lifan Cao, Junyan Sun, Shumei Li, Linlin Song, Halyna Zhatova, Shuhan Liu, Shengli Tong, Mingming Tang, Zongli Chu, Yanlin Yang, Liping Dong","doi":"10.1111/pce.70915","DOIUrl":"10.1111/pce.70915","url":null,"abstract":"<p><p>Soil heavy metal contamination-including cadmium (Cd), arsenic (As), lead (Pb), mercury (Hg), zinc (Zn) excess, and copper (Cu) excess-poses a critical threat to sustainable agriculture and food safety. Membrane transport proteins serve as primary interfaces governing ion entry, subcellular compartmentalization, and long-distance redistribution. This review integrates recent advances across multiple scales to construct a unified regulatory framework: (i) at the cell periphery, plasma membrane transporters of the NRAMP, ZIP, and COPT families mediate metal influx, whereas efflux transporters and cell wall modifications limit cytosolic accumulation; (ii) at the subcellular level, vacuolar HMA and ABCC transporters drive sequestration, coordinated by COPII-mediated forward trafficking, ESCRT-dependent turnover, and autophagy-based quality control; (iii) at the signaling level, Ca²⁺-ROS-MAPK cascades and lipid microdomain dynamics modulate transporter activity through phosphorylation and endocytic sorting; and (iv) at the whole-plant level, xylem-phloem transport and systemic signals (Ca²⁺ waves, ROS, jasmonic acid) coordinate root-shoot communication. The strength of evidence distinguishing in planta validation from heterologous inference is critically evaluated, the biological trade-offs associated with transporter manipulation are addressed, and species-specific strategies contrasting hyperaccumulators with low-accumulation food crops are discussed. Finally, the potential of cryo-electron microscopy (cryo-EM), single-cell transcriptomics, genetically encoded sensors, and rhizosphere engineering in reshaping this field is outlined. This synthesis aims to provide a roadmap for developing crops with low metal accumulation and high stress tolerance through precision breeding and gene editing.</p>","PeriodicalId":222,"journal":{"name":"Plant, Cell & Environment","volume":" ","pages":"10576-10589"},"PeriodicalIF":6.9,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149035932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Contemporary Initial Glucose-Lowering Strategies for Type 2 Diabetes: A Systematic Review and Bayesian Network Meta-Analysis.","authors":"Gabriel Cavalcante Lima Chagas, Mayara Rios Leite Macedo Monteiro, Marina Loch Eira, Gaspar R Chiappa, Joaquim Silva Custódio, Marconi Abreu","doi":"10.1111/dom.71397","DOIUrl":"10.1111/dom.71397","url":null,"abstract":"<p><strong>Aims: </strong>To compare contemporary initial glucose-lowering strategies in adults with type 2 diabetes who were treatment-naïve or had completed adequate washout.</p><p><strong>Materials and methods: </strong>We searched MEDLINE, Embase and the Cochrane Library from inception to 20 September 2025 for randomized trials comparing sodium-glucose cotransporter 2 inhibitor (SGLT2i) monotherapy, glucagon-like peptide-1 receptor agonist (GLP-1 RA) or dual incretin agonist monotherapy, SGLT2i plus metformin or placebo. Two reviewers independently selected studies and verified extracted data. Bayesian random-effects network meta-analysis was used.</p><p><strong>Results: </strong>Twenty randomized trials with 8947 participants were included; all were at low risk of bias. Compared with placebo, SGLT2i plus metformin produced the largest HbA1c reduction (mean difference [MD] -1.36%, 95% credible interval [CrI] -1.91 to -0.82), followed by GLP-1 RA or dual incretin agonist monotherapy (MD -1.25%, 95% CrI -1.68 to -0.83) and SGLT2i monotherapy (MD -0.76%, 95% CrI -1.10 to -0.41). Achievement of HbA1c < 7% and fasting plasma glucose reduction showed a similar pattern. GLP-1 RA or dual incretin agonist monotherapy produced the greatest body weight percentage reduction (MD -4.74%, 95% CrI -6.71 to -2.90). Active-treatment comparisons were indirect, and baseline HbA1c was higher in the SGLT2i plus metformin node. Certainty of evidence was low or very low across key comparisons.</p><p><strong>Conclusions: </strong>SGLT2i plus metformin and GLP-1 RA or dual incretin agonist therapy are both reasonable contemporary initial glucose-lowering strategies for type 2 diabetes. Selection between these strategies should take into consideration phenotype, treatment priorities, tolerability, cost, access and patient preference.</p><p><strong>Trial registration: </strong>PROSPERO: CRD420251178714.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":"11862-11871"},"PeriodicalIF":6.1,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149079045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}