Silvio E Inzucchi1, Kieran F Docherty2, Lars Køber3, Mikhail N Kosiborod4, Felipe A Martinez5, Piotr Ponikowski6, Marc S Sabatine7, Scott D Solomon8, Subodh Verma9, Jan Bělohlávek10, Michael Böhm11, Chern-En Chiang12, Rudolf A de Boer13, Mirta Diez14, Andre Dukát15, Charlotta E A Ljungman16, Olof Bengtsson17, Anna Maria Langkilde17, Mikaela Sjöstrand17, Pardeep S Jhund2, John J V McMurray. 1. Section of Endocrinology, Yale University School of Medicine, New Haven, CT silvio.inzucchi@yale.edu. 2. BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, U.K. 3. Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. 4. Saint Luke's Mid America Heart Institute and University of Missouri-Kansas City, Kansas City, MO. 5. National University of Cordoba, Cordoba, Argentina. 6. Wroclaw Medical University, Wroclaw, Poland. 7. TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA. 8. Cardiovascular Division, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA. 9. Division of Cardiac Surgery, St Michael's Hospital, University of Toronto, Toronto, Ontario, Canada. 10. 2nd Department of Medicine - Cardiovascular Medicine, 1st Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic. 11. Internal Medicine Clinic III (Böhm), Saarland University Medical Center, Homburg/Saar, Germany. 12. General Clinical Research Center, and Division of Cardiology, Taipei Veterans General Hospital and National Yang-Ming University, Taipei, Taiwan. 13. Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. 14. Division of Cardiology, Instituto Cardiovascular de Buenos Aires, Buenos Aires, Argentina. 15. Fifth Department of Internal Medicine, Comenius University in Bratislava, Bratislava, Slovakia. 16. Department of Molecular and Clinical Medicine and Cardiology, Sahlgrenska Academy, Gothenburg, Sweden. 17. AstraZeneca, Gothenburg, Sweden.
Abstract
OBJECTIVE: The sodium-glucose cotransporter 2 inhibitor dapagliflozin reduced the risk of cardiovascular mortality and worsening heart failure in the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) trial. This report explores the effect of dapagliflozin on incident type 2 diabetes (T2D) in the cohort without diabetes enrolled in the trial. RESEARCH DESIGN AND METHODS: The subgroup of 2,605 patients with heart failure and reduced ejection fraction (HFrEF), no prior history of diabetes, and an HbA1c of <6.5% at baseline was randomized to dapagliflozin 10 mg daily or placebo. In this exploratory analysis, surveillance for new-onset diabetes was accomplished through periodic HbA1c testing as part of the study protocol and comparison between the treatment groups assessed through a Cox proportional hazards model. RESULTS: At baseline, the mean HbA1c was 5.8%. At 8 months, there were minimal changes, with a placebo-adjusted change in the dapagliflozin group of -0.04%. Over a median follow-up of 18 months, diabetes developed in 93 of 1,307 patients (7.1%) in the placebo group and 64 of 1,298 (4.9%) in the dapagliflozin group. Dapagliflozin led to a 32% reduction in diabetes incidence (hazard ratio 0.68, 95% CI 0.50-0.94; P = 0.019). More than 95% of the participants who developed T2D had prediabetes at baseline (HbA1c 5.7-6.4%). Participants who developed diabetes in DAPA-HF had a higher subsequent mortality than those who did not. CONCLUSIONS: In this exploratory analysis among patients with HFrEF, treatment withdapagliflozin reduced the incidence of new diabetes. This potential benefit needs confirmation in trials of longer duration and in people without heart failure.
RCT Entities:
OBJECTIVE: The sodium-glucose cotransporter 2 inhibitor dapagliflozin reduced the risk of cardiovascular mortality and worsening heart failure in the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) trial. This report explores the effect of dapagliflozin on incident type 2 diabetes (T2D) in the cohort without diabetes enrolled in the trial. RESEARCH DESIGN AND METHODS: The subgroup of 2,605 patients with heart failure and reduced ejection fraction (HFrEF), no prior history of diabetes, and an HbA1c of <6.5% at baseline was randomized to dapagliflozin 10 mg daily or placebo. In this exploratory analysis, surveillance for new-onset diabetes was accomplished through periodic HbA1c testing as part of the study protocol and comparison between the treatment groups assessed through a Cox proportional hazards model. RESULTS: At baseline, the mean HbA1c was 5.8%. At 8 months, there were minimal changes, with a placebo-adjusted change in the dapagliflozin group of -0.04%. Over a median follow-up of 18 months, diabetes developed in 93 of 1,307 patients (7.1%) in the placebo group and 64 of 1,298 (4.9%) in the dapagliflozin group. Dapagliflozin led to a 32% reduction in diabetes incidence (hazard ratio 0.68, 95% CI 0.50-0.94; P = 0.019). More than 95% of the participants who developed T2D had prediabetes at baseline (HbA1c 5.7-6.4%). Participants who developed diabetes in DAPA-HF had a higher subsequent mortality than those who did not. CONCLUSIONS: In this exploratory analysis among patients with HFrEF, treatment with dapagliflozin reduced the incidence of new diabetes. This potential benefit needs confirmation in trials of longer duration and in people without heart failure.
Authors: Tran Kim Son; Ngo Hoang Toan; Nguyen Thang; Huynh Le Trong Tuong; Hoang Anh Tien; Nguyen Hai Thuy; Huynh Van Minh; Paul Valensi Journal: Cardiovasc Diabetol Date: 2022-05-14 Impact factor: 8.949
Authors: Osamah M Alfayez; Alanoud A Alsallum; Adnan F Aljabri; Faisal S Almutairi; Ola Al-Azzeh; Ohoud S Almalki; Majed S Al Yami; Omar A Almohammed Journal: Front Public Health Date: 2022-09-08
Authors: Nicolas Isaza; Paola Calvachi; Inbar Raber; Chia-Liang Liu; Brandon K Bellows; Inmaculada Hernandez; Changyu Shen; Michael C Gavin; A Reshad Garan; Dhruv S Kazi Journal: JAMA Netw Open Date: 2021-07-01