{"title":"新型降糖药对老年2型糖尿病患者心血管疗效的比较：一项目标试验模拟队列研究","authors":"Vanja Kosjerina, Motahareh Parsa, Stine Hedegaard Scheuer, Mikkel Zöllner Ankarfeldt, Kathrine Kold Sørensen, Birgitte Brock, Dorte Vistisen, Kim Katrine Bjerring Clemmensen, Jørgen Rungby","doi":"10.1016/j.eclinm.2025.103162","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Reducing risk of cardiovascular disease is crucial in managing type 2 diabetes (T2D). This study assessed the comparative cardiovascular effectiveness of newer glucose-lowering drugs in real-world elderly individuals with T2D, and examined how age modified these effects.</p><p><strong>Methods: </strong>We conducted a cohort study using Danish nationwide registries to emulate a three-arm randomized clinical trial. Participants aged ≥70 years were new users of glucagon-like peptide 1 receptor agonists (GLP1-RAs), sodium-glucose cotransporter 2 inhibitors (SGLT-2is), or dipeptidyl peptidase 4 inhibitors (DPP-4is), between 2012 and 2020. We estimated the overall and age-specific incidence rate ratios (IRR) of 3-point major adverse cardiovascular events (3P-MACE) and hospitalization for heart failure (HHF) using Poisson regression models. Summarized weights were used to balance baseline characteristics and treatment adherence.</p><p><strong>Findings: </strong>The study included 35,679 participants (DPP-4is: 21,848 (62%), GLP1-RAs: 5702 (16%), SGLT-2is: 8129 (23%)). In the as-treated analysis, GLP1-RAs and SGLT-2is were associated with significantly reduced rates of 3P-MACE and HHF compared to DPP-4is. The overall IRR for 3P-MACE was 0.68 (95% CI 0.65-0.71) (GLP1-RAs vs. DPP4is) and 0.65 (95% CI 0.63-0.68) (SGLT-2is vs. DPP4is), while for HHF the IRR was 0.81 (95% CI 0.74-0.88) (GLP1-RAs vs. DPP4is) and 0.60 (95% CI 0.55-0.66) (SGLT-2is vs. DPP4is). These effects were predominantly independent of age. No significant difference was observed between SGLT-2is and GLP1-RAs on 3P-MACE, however, SGLT-2is were associated with a significant reduction of HHF, compared to GLP1-RAs, with an overall IRR of 0.75 (95% CI 0.67-0.83), and with age-dependent variations for both outcomes.</p><p><strong>Interpretation: </strong>In the elderly, use of GLP1-RAs and SGLT-2is was associated with reduced rates of 3P-MACE and HHF compared to DPP-4is, independent of age. SGLT-2is were also associated with reduced rates of HHF compared to GLP1-RAs, largely independent of age, in this population of individuals aged 70 years and above. This provides real-world evidence on the comparative cardiovascular effectiveness of the three most recent glucose-lowering medications and may help strengthen implementation of guidelines into clinical practice.</p><p><strong>Funding: </strong>None.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"82 ","pages":"103162"},"PeriodicalIF":9.6000,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11976231/pdf/","citationCount":"0","resultStr":"{\"title\":\"Comparative cardiovascular effectiveness of newer glucose-lowering drugs in elderly with type 2 diabetes: a target trial emulation cohort study.\",\"authors\":\"Vanja Kosjerina, Motahareh Parsa, Stine Hedegaard Scheuer, Mikkel Zöllner Ankarfeldt, Kathrine Kold Sørensen, Birgitte Brock, Dorte Vistisen, Kim Katrine Bjerring Clemmensen, Jørgen Rungby\",\"doi\":\"10.1016/j.eclinm.2025.103162\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Reducing risk of cardiovascular disease is crucial in managing type 2 diabetes (T2D). 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In the as-treated analysis, GLP1-RAs and SGLT-2is were associated with significantly reduced rates of 3P-MACE and HHF compared to DPP-4is. The overall IRR for 3P-MACE was 0.68 (95% CI 0.65-0.71) (GLP1-RAs vs. DPP4is) and 0.65 (95% CI 0.63-0.68) (SGLT-2is vs. DPP4is), while for HHF the IRR was 0.81 (95% CI 0.74-0.88) (GLP1-RAs vs. DPP4is) and 0.60 (95% CI 0.55-0.66) (SGLT-2is vs. DPP4is). These effects were predominantly independent of age. No significant difference was observed between SGLT-2is and GLP1-RAs on 3P-MACE, however, SGLT-2is were associated with a significant reduction of HHF, compared to GLP1-RAs, with an overall IRR of 0.75 (95% CI 0.67-0.83), and with age-dependent variations for both outcomes.</p><p><strong>Interpretation: </strong>In the elderly, use of GLP1-RAs and SGLT-2is was associated with reduced rates of 3P-MACE and HHF compared to DPP-4is, independent of age. 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引用次数: 0
摘要
背景：降低心血管疾病的风险是控制2型糖尿病（T2D）的关键。本研究评估了较新的降糖药物对现实世界中老年T2D患者的心血管效果，并研究了年龄如何改变这些效果。方法：我们使用丹麦全国注册中心进行了一项队列研究，以模拟三组随机临床试验。年龄≥70岁的参与者是2012年至2020年间新使用胰高血糖素样肽1受体激动剂（GLP1-RAs）、钠-葡萄糖共转运蛋白2抑制剂（SGLT-2is）或二肽基肽酶4抑制剂（DPP-4is）的患者。我们使用泊松回归模型估计了3点主要不良心血管事件（3P-MACE）和心力衰竭（HHF）住院的总体和年龄特异性发病率比（IRR）。汇总权重用于平衡基线特征和治疗依从性。研究结果：该研究包括35,679名参与者(DPP-4is: 21,848 (62%), GLP1-RAs: 5702 （16%), SGLT-2is: 8129(23%)）。在治疗后的分析中，与DPP-4is相比，GLP1-RAs和SGLT-2is与显著降低的3P-MACE和HHF发生率相关。3P-MACE的总IRR为0.68 (95% CI 0.65-0.71) （GLP1-RAs vs. DPP4is）和0.65 (95% CI 0.63-0.68) (SGLT-2is vs. DPP4is)，而HHF的IRR为0.81 (95% CI 0.74-0.88) （GLP1-RAs vs. DPP4is）和0.60 (95% CI 0.55-0.66) （SGLT-2is vs. DPP4is）。这些影响主要与年龄无关。SGLT-2is和GLP1-RAs在3P-MACE上没有观察到显著差异，然而，与GLP1-RAs相比，SGLT-2is与HHF的显著降低相关，总体IRR为0.75 (95% CI 0.67-0.83)，并且两种结果都存在年龄依赖性变化。解释：在老年人中，与DPP-4is相比，GLP1-RAs和SGLT-2is的使用与3P-MACE和HHF的发生率降低相关，与年龄无关。与GLP1-RAs相比，SGLT-2is也与HHF发生率降低相关，在很大程度上与年龄无关，在70岁及以上的人群中。这为比较三种最新降糖药物的心血管有效性提供了真实的证据，并可能有助于加强指南在临床实践中的实施。资金:没有。
Comparative cardiovascular effectiveness of newer glucose-lowering drugs in elderly with type 2 diabetes: a target trial emulation cohort study.
Background: Reducing risk of cardiovascular disease is crucial in managing type 2 diabetes (T2D). This study assessed the comparative cardiovascular effectiveness of newer glucose-lowering drugs in real-world elderly individuals with T2D, and examined how age modified these effects.
Methods: We conducted a cohort study using Danish nationwide registries to emulate a three-arm randomized clinical trial. Participants aged ≥70 years were new users of glucagon-like peptide 1 receptor agonists (GLP1-RAs), sodium-glucose cotransporter 2 inhibitors (SGLT-2is), or dipeptidyl peptidase 4 inhibitors (DPP-4is), between 2012 and 2020. We estimated the overall and age-specific incidence rate ratios (IRR) of 3-point major adverse cardiovascular events (3P-MACE) and hospitalization for heart failure (HHF) using Poisson regression models. Summarized weights were used to balance baseline characteristics and treatment adherence.
Findings: The study included 35,679 participants (DPP-4is: 21,848 (62%), GLP1-RAs: 5702 (16%), SGLT-2is: 8129 (23%)). In the as-treated analysis, GLP1-RAs and SGLT-2is were associated with significantly reduced rates of 3P-MACE and HHF compared to DPP-4is. The overall IRR for 3P-MACE was 0.68 (95% CI 0.65-0.71) (GLP1-RAs vs. DPP4is) and 0.65 (95% CI 0.63-0.68) (SGLT-2is vs. DPP4is), while for HHF the IRR was 0.81 (95% CI 0.74-0.88) (GLP1-RAs vs. DPP4is) and 0.60 (95% CI 0.55-0.66) (SGLT-2is vs. DPP4is). These effects were predominantly independent of age. No significant difference was observed between SGLT-2is and GLP1-RAs on 3P-MACE, however, SGLT-2is were associated with a significant reduction of HHF, compared to GLP1-RAs, with an overall IRR of 0.75 (95% CI 0.67-0.83), and with age-dependent variations for both outcomes.
Interpretation: In the elderly, use of GLP1-RAs and SGLT-2is was associated with reduced rates of 3P-MACE and HHF compared to DPP-4is, independent of age. SGLT-2is were also associated with reduced rates of HHF compared to GLP1-RAs, largely independent of age, in this population of individuals aged 70 years and above. This provides real-world evidence on the comparative cardiovascular effectiveness of the three most recent glucose-lowering medications and may help strengthen implementation of guidelines into clinical practice.
期刊介绍：
eClinicalMedicine is a gold open-access clinical journal designed to support frontline health professionals in addressing the complex and rapid health transitions affecting societies globally. The journal aims to assist practitioners in overcoming healthcare challenges across diverse communities, spanning diagnosis, treatment, prevention, and health promotion. Integrating disciplines from various specialties and life stages, it seeks to enhance health systems as fundamental institutions within societies. With a forward-thinking approach, eClinicalMedicine aims to redefine the future of healthcare.
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