Type 2 diabetes, sodium-glucose cotransporter-2 inhibitors and cardiovascular outcomes: real world evidence versus a randomised clinical trial.

IF 10.6 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Cardiovascular Diabetology Pub Date : 2025-09-30 DOI:10.1186/s12933-025-02924-0

Puriya Daniel Würtz Yazdanfard, Kathrine Kold Sørensen, Bochra Zareini, Ulrik Pedersen-Bjergaard, Johan Sebastian Ohlendorff, Anders Munch, Mikkel Porsborg Andersen, Rasmus Bo Hasselbalch, Henrik Imberg, Viktor Tasseleus, Marcus Lind, Jonathan Valabhji, Pratik Choudhary, Kamlesh Khunti, Stefanie Schmid, Stefanie Lanzinger, Julia Mader, Thomas Alexander Gerds, Christian Torp-Pedersen

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引用次数: 0

Abstract

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have demonstrated cardiovascular benefits in randomised controlled trials (RCT). However, the controlled nature of RCTs and the selected trial populations limit their generalizability to real-world practice. Substantial methodological advances now enable robust estimation of absolute risks, risk differences, and continuous on-treatment effects, providing more clinically interpretable measures of SGLT2i effectiveness than previously possible with traditional models reliant on hazard ratios.

Methods: We conducted a target trial emulation using nationwide Danish registries to evaluate the real-world effectiveness of SGLT2i versus dipeptidyl peptidase-4 inhibitors (DPP4i) in individuals with type 2 diabetes (T2D) and cardiovascular disease (CVD). Outcomes included major adverse cardiovascular events (MACE), heart failure hospitalizations, and all-cause mortality. Absolute risks and risk differences for three years of continuous treatment were estimated using longitudinal targeted minimum loss-based estimation, adjusting for baseline and time-varying confounders.

Results: Among 116,823 patients who redeemed SGLT2i or DPP4i for the first time, 13,524 met inclusion and exclusion criteria (SGLT2i: 6,025; DPP4i: 7,499). At three years, the risk of MACE was 11.5% for SGLT2i users versus 14.2% for DPP4i users (risk-difference: 2.8 percentage-points, 95% CI: 1.1-4.4%). Heart failure hospitalizations were lower by 5.1 percentage-points (95% CI: 4.3-6.0%), and all-cause mortality by 3.1 percentage-points (95% CI: 1.5-4.7%), all favoring SGLT2i. Notably, we also observed a risk reduction in stroke by 2.4 percentage-points (95% CI: 1.7-3.1%).

Conclusions: This study demonstrates the real-world effectiveness of continuous SGLT2i treatment in reducing cardiovascular events in patients with T2D and CVD. The absolute benefit of SGLT2i was larger in a real world population than in the intention to treat estimate in clinical trials.

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2型糖尿病、钠-葡萄糖共转运蛋白2抑制剂和心血管结局：真实世界证据与随机临床试验对比

背景：钠-葡萄糖共转运蛋白-2抑制剂（SGLT2i）在随机对照试验（RCT）中显示出心血管益处。然而，随机对照试验的受控性质和选定的试验人群限制了它们在现实世界实践中的推广能力。现在，方法上的实质性进步使绝对风险、风险差异和持续治疗效果的可靠估计成为可能，与以前依赖于风险比的传统模型相比，提供了更多临床可解释的SGLT2i有效性测量。方法：我们在丹麦全国范围内进行了一项目标试验模拟，以评估SGLT2i与二肽基肽酶-4抑制剂（DPP4i）在2型糖尿病（T2D）和心血管疾病（CVD）患者中的实际有效性。结果包括主要不良心血管事件（MACE）、心力衰竭住院和全因死亡率。使用纵向目标最小损失估计，调整基线和时变混杂因素，估计连续治疗三年的绝对风险和风险差异。结果：在116,823例首次使用SGLT2i或DPP4i的患者中，13,524例符合纳入和排除标准（SGLT2i: 6,025例；DPP4i: 7,499例）。三年后，SGLT2i患者的MACE风险为11.5%，而DPP4i患者的MACE风险为14.2%（风险差异：2.8个百分点，95% CI: 1.1-4.4%）。心力衰竭住院率降低5.1个百分点（95% CI: 4.3-6.0%），全因死亡率降低3.1个百分点（95% CI: 1.5-4.7%），均有利于SGLT2i。值得注意的是，我们还观察到卒中风险降低了2.4个百分点（95% CI: 1.7-3.1%）。结论：本研究证明了SGLT2i持续治疗在减少T2D和CVD患者心血管事件方面的实际有效性。SGLT2i在现实世界人群中的绝对获益大于临床试验中意向治疗估计。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cardiovascular Diabetology 医学-内分泌学与代谢

CiteScore

12.30

自引率

15.10%

发文量

240

审稿时长

1 months

期刊介绍： Cardiovascular Diabetology is a journal that welcomes manuscripts exploring various aspects of the relationship between diabetes, cardiovascular health, and the metabolic syndrome. We invite submissions related to clinical studies, genetic investigations, experimental research, pharmacological studies, epidemiological analyses, and molecular biology research in this field.