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
{"title":"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","authors":"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","doi":"10.1186/s12933-025-02924-0","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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%).</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"24 1","pages":"371"},"PeriodicalIF":10.6000,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12487220/pdf/","citationCount":"0","resultStr":"{\"title\":\"Type 2 diabetes, sodium-glucose cotransporter-2 inhibitors and cardiovascular outcomes: real world evidence versus a randomised clinical trial.\",\"authors\":\"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\",\"doi\":\"10.1186/s12933-025-02924-0\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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%).</p><p><strong>Conclusions: </strong>This study demonstrates the real-world effectiveness of continuous SGLT2i treatment in reducing cardiovascular events in patients with T2D and CVD. 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Type 2 diabetes, sodium-glucose cotransporter-2 inhibitors and cardiovascular outcomes: real world evidence versus a randomised clinical trial.
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.
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.
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