Effects of dapagliflozin in type 2 diabetes and heart failure with mildly reduced or preserved ejection fraction across the background of glucose-lowering therapy in DELIVER

Presented at the EASD annual meeting 2023 by: Silvio Inzucchi, MD - New Haven, CT, USA

Introduction and methods

The DELIVER trial was a randomized, double-blind, placebo-controlled trial, in which patients ≥40 years of age with NYHA class II-IV, LVEF>40%, structural heart disease, and elevated natriuretic peptides were enrolled. A total of 6263 patients were randomized to dapagliflozin or placebo. After a median duration of 2.3 year (IQR 1.7-2.8), the primary endpoint of time to CV death or worsening HF was reduced in the dapagliflozin group compared with the placebo group (HR 0.82, 95%CI:0.73-0.92, P=0.0008). In a subgroup analysis was shown that this effect was similar in patients with and without T2D at baseline.

This translated into a class I recommendation of dapagliflozin and empagliflozin for the management of patients with HFmrEF or HFpEF in the updated 2023 ESC HF guidelines and class 2a recommendations in the 2022 AHA/ACC/HFSA HF guidelines.

Approximately half of the DELIVER population had T2D (50.2%), and the majority of these patients used glucose-lowering therapy (77.1%). It is unknown whether the effects of dapagliflozin on outcomes in DELIVER are influenced by baseline type or number of glucose-lowering therapies. These data may help to inform evidence-based guidelines for the treatment of T2D in the HFpEF/HFmrEF population.

Main results

• The treatment effect of dapagliflozin with respect to the primary composite outcome was irrespective of the number of glucose-lowering therapies (P=0.582).
• When studying treatment effects of dapagliflozin on the primary outcome in subgroups of users of metformin, insulin, sulphonyl urea, DPP-4i, GLP-1RA, no significant P values for interaction were found, except for the group of sulphonyl urea users. The treatment effect of dapagliflozin was larger in patients using sulphonyl urea (Pinteraction=0.003), which appeared to be driven by reduction in CV death and all-cause death.

Conclusion

In this post-hoc analysis of patients with T2D and HFpEF/HFmrEF in the DELIVER trial, there was no heterogeneity in the treatment effect of dapagliflozin across the spectrum of number of anti-glucose lowering therapies and no consistent heterogeneity observed by background use of metformin, insulin, DPP4i or GLP-1RA. Heterogeneity for the primary outcome by baseline use of sulphonyl urea was observed, with larger benefit of dapagliflozin in patients using sulphonyl urea. According to Inzucchi, this may reflect the play of chance but could warrant further investigation.

Silvio Inzucchi concluded: “These data support newer T2D treatment guidelines that do no longer mandate foundational therapy with metformin in those with HF. Furthermore, the benefits of dapagliflozin appear not to be mitigated by concurrent insulin therapy, which can have sodium-retentive properties”.

- Our reporting is based on the information provided at the EASD annual meeting -

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