Impact of empagliflozin on insulin needs in patients with heart failure and diabetes: An EMPEROR‐Pooled analysis

Author:

Talha Khawaja M.1ORCID,Green Jennifer2,Filippatos Gerasimos34,Pocock Stuart5,Zannad Faiez6,Brueckmann Martina7,Schueler Elke8,Ofstad Anne Pernille910,Ferreira João Pedro11ORCID,Anker Stefan D.12,Butler Javed113ORCID,Rosenstock Julio14ORCID,Packer Milton1516

Affiliation:

1. Department of Medicine University of Mississippi Medical Center Jackson Mississippi USA

2. Division of Endocrinology, Metabolism, and Nutrition Duke University Durham North Carolina USA

3. Department of Cardiology National and Kapodistrian University of Athens Athens Greece

4. Department of Cardiology Athens University Hospital Attikon Athens Greece

5. Department of Medical Statistics London School of Hygiene and Tropical Medicine London UK

6. Université de Lorraine, Inserm Centre d'Investigations Cliniques, Plurithématique 1433, CHRU Nancy Nancy France

7. Boehringer Ingelheim International GmbH, Ingelheim, Germany and First Department of Medicine, Faculty of Medicine Mannheim University of Heidelberg Mannheim Germany

8. mainanalytics GmbH Sulzbach Germany

9. Boehringer Ingelheim Norway KS Asker Norway

10. Oslo Diabetes Research Center Oslo Norway

11. UnIC@RISE, Cardiovascular Research and Development Center, Department of Surgery and Physiology Faculty of Medicine of the University of Porto, Porto, Portugal and Heart Failure Clinic, Internal Medicine Department, Centro Hospitalar de Vila Nova de Gaia/Espinho, Vila Nova de Gaia, Portugal and Université de Lorraine, INSERM, Centre d'Investigations Cliniques Plurithématique 1433, and INSERM U1116, CHRU, F‐CRIN INI‐CRCT (Cardiovascular and Renal Clinical Trialists) Nancy France

12. Department of Cardiology (CVK); and Berlin Institute of Health Center for Regenerative Therapies (BCRT); German Centre for Cardiovascular Research (DZHK) partner site Berlin Charité Universitätsmedizin Berlin Berlin Germany

13. Baylor Scott and White Research Institute Dallas Texas USA

14. Velocity Clinical Research at Medical City Dallas Texas USA

15. Baylor University Medical Center Dallas Texas USA

16. Imperial College London UK

Abstract

AbstractAimTo assess the effect of empagliflozin on patients with comorbid heart failure (HF) and diabetes with or without baseline insulin, and to study the impact of empagliflozin on insulin requirements over time.Materials and MethodsWe performed a post‐hoc analysis of pooled patient‐level data from two cardiovascular outcomes trials of empagliflozin in HF (EMPEROR‐Reduced and EMPEROR‐Preserved trials). We undertook a subgroup analysis stratified by baseline insulin use, including all patients with diabetes. The studied endpoints included the primary composite endpoint of first hospitalization for HF or cardiovascular death, rate of decline of estimated glomerular filtration rate, composite renal outcome and rates of sustained insulin initiation.ResultsAmong 4794 patients with diabetes, 1333 (658 in empagliflozin, 675 in placebo) were using insulin at baseline. The treatment effect of empagliflozin on the primary endpoint was consistent irrespective of insulin use [no insulin, hazard ratio 0.74, 95% confidence interval (CI) 0.63‐0.86; using insulin, hazard ratio 0.81, 95% CI 0.66‐1.00, pinteraction = .49], as was the effect on the rate of decline of the estimated glomerular filtration rate (pinteraction = .75). There was no effect of empagliflozin on the composite renal outcome in patients using or not using insulin (pinteraction = .30). Among patients not using insulin at baseline, those randomized to empagliflozin initiated insulin less frequently throughout the follow‐up period compared with those receiving placebo (2.6% vs. 3.8%, odds ratio 0.66, 95% CI 0.50‐0.88).ConclusionsEmpagliflozin exerts a consistent benefit on cardiovascular outcomes and renal function decline, irrespective of baseline insulin use, and reduces the need for sustained insulin initiation in patients with HF and diabetes.

Funder

Boehringer Ingelheim

Publisher

Wiley

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