SGLT Inhibitors for Heart Failure by Duration of Diabetes: ESC 2024

Regardless of duration of type 2 diabetes, sodium-glucose cotransporter inhibitors prevented cardiovascular events.

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Patients with diabetes are 2 to 4 times more likely to develop heart failure as someone without diabetes,¹ highlighting the importance of treatment for patients with diabetes and a high cardiovascular risk.

Two abstracts presented at the European Society of Cardiology (ESC) Congress 2024 analyzed the effects of sodium-glucose cotransporter (SGLT) inhibitors in preventing cardiovascular events based on duration of type 2 diabetes (T2D).

Sotagliflozin: secondary analysis of SCORED

Approved in May 2023,² sotagliflozin (Inpefa) is a dual SGLT1/2 inhibitor. The SCORED trial (NCT03315143) randomized patients with T2D and high cardiovascular risk to sotagliflozin or placebo, and a secondary analysis of the benefit based on diabetes duration was presented at ESC.³ Results of the SCORED trial were initially published in New England Journal of Medicine in 2020 and found a lower risk of deaths from cardiovascular causes, hospitalizations for heart failure, and urgent care visits for heart failure.⁴

Nearly all of the patients in SCORED (99.9%; 10,579 of 10,584 patients) had complete data on diabetes duration, with 2412 (22.8%) patients having duration of less than 10 years, 4424 (41.8%) a duration of 10 to 19 years, and 3743 (25.9%) a duration of 20 years or more. The median hemoglobin A_1C (HbA_1c) was 8.6% for the < 10 years group, 8.7% for the 10-19 years group, and 8.7% for the ≥ 20 years group.

The primary end point was total cardiovascular death, hospitalization for heart failure, or urgent care visit for heart failure. The rate of the primary end point was lower in patients taking sotagliflozin at 5.6 events per 100 patient-years compared with 7.5 events per 100 patient-years in the placebo group.

There was an increased relative treatment benefit with increasing diabetes duration with 5.6 events in the < 10 years group, 6.1 events in the 10-19 years group, and 4.6 events in the ≥ 20 years group.

Total major adverse cardiovascular events (total cardiovascular death, nonfatal stroke, and nonfatal myocardial infarction) were lower in the sotagliflozin group with 4.8 events per 100 patient-years compared with 6.3 events in the placebo group.

Dapagliflozin: meta-analysis of DAPA-HF and DELIVER

A patient-level pooled analysis of the DAPA-HF (NCT03036124) and DELIVER (NCT03619213) trials investigated the efficacy and safety of another SGLT2 inhibitor, dapagliflozin (Farxiga), in patients with heart failure based on the duration of their T2D.⁵

The results of DAPA-HF were first published in 2019, and the results of DELIVER first published in 2022.^6,7

A total of 4784 patients were analyzed. Of them, 1879 (39.3%) had T2D less than 5 years, 1074 (22.4%) had a duration of 5 to 10 years, and 1831 (38.3%) had a duration of greater than 11 years. The primary outcome was a composite of worsening heart failure of cardiovascular death.

Patients with a longer duration of diabetes tended to be female, older, and White with a higher HbA_1c, body mass index, and left ventricular ejection fraction. While patients with a longer duration of diabetes also had a longer duration of heart failure, they were no more likely to have had a prior heart failure hospitalization or worse New York Heart Association functional class.

There was a benefit across duration groups on the primary outcome: < 5 years had an HR of 0.85 (95% CI, 0.69-1.04), 5 to 10 years had an HR of 0.65 (95% CI, 0.51-0.83), and > 11 years had an HR of 0.84 (95% CI, 0.70-1.01).

“Dapagliflozin reduced the risk of worsening [heart failure] or cardiovascular death, and improved symptoms, in patients with [heart failure] and T2D, irrespective of T2D duration,” the researchers concluded.

References

1. Diabetes and heart failure are linked; treatment should be too. American Heart Association. June 6, 2019. Accessed August 29, 2024. https://www.heart.org/en/news/2019/06/06/diabetes-and-heart-failure-are-linked-treatment-should-be-too

2. Inserro A. FDA approves sotagliflozin, a dual SGLT1/2 inhibitor, for full range of heart failure. AJMC^®. May 27, 2023. Accessed August 29, 2024. https://www.ajmc.com/view/fda-sotagliflozin-a-dual-sglt1-2-inhibitor-for-full-range-of-heart-failure

3. Aggarwal R, BhattD, Szarek M, et al Efficacy of sotagliflozin by diabetes duration: a secondary analysis of SCORED. Presented at: ESC Congress 2024; August 30 to September 2, 2024; London, England.

4. Bhatt D, Szarek M, Pitt B, et al; SCORED investigators. Sotagliflozin in patients with diabetes and chronic kidney disease. N Engl J Med. 2021;384(2):129-139. doi:10.1056/NEJMoa2030186

5. Butt J, De Boer RA, Hernandez A, et al. Effects of dapagliflozin in heart failure according to duration of type 2 diabetes: a patient-level meta-analysis of DAPA-HF and DELIVER. Presented at: ESC Congress 2024; August 30 to September 2, 2024; London, England.

6. McMurray JJV, Solomon SD, Inzucchi SE, et al; DAPA-HF trial committees and investigators. Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med. 2019;381(21):1995-2008. doi:10.1056/NEJMoa1911303

7. Solomon SD, McMurray JJV, Claggett B, et al; DELIVER trial committees and investigators. Dapagliflozin in heart failure with mildly reduced or preserved ejection fraction. N Engl J Med. 2022;387(12):1089-1098. doi:10.1056/NEJMoa2206286