Neuropathy Impact on Outcomes and Efficacy in HF Patients with Type 2 Diabetes: Insights from DAPA-HF and DELIVER Trials

New research found that Dapagliflozin reduces the relative and absolute risk of death and heart failure-related hospitalization due to diabetic neuropathy in individuals with Heart failure and Type 2 Diabetes. The trial results were published in the journal JACC: Heart Failure.

Diabetic neuropathy is one of the common complications of diabetes seen more in long-standing and poorly controlled diseases. Individuals with diabetic neuropathy can have worsened outcomes like a higher incidence of cardiovascular disease, including heart failure (HF) than those without. However, the relationship between neuropathy and clinical outcomes in patients with both diabetes and heart failure is not clearly understood. Additionally, it remains unclear whether neuropathy could affect the efficacy of heart failure treatments. To understand this better, researchers from Europe and America studied the effects on Diabetics.

Researchers conducted a post hoc analysis of two major heart failure trials: the DAPA-HF and DELIVER studies involving over 5,000 patients with HF and type 2 diabetes (T2D). Both trials were randomized, double-blind, and placebo-controlled, evaluating the effectiveness and safety of dapagliflozin, a medication used to treat heart failure, at a dose of 10 mg once daily. The key difference between the trials was the criteria for left ventricular ejection fraction (LVEF), with DAPA-HF enrolling patients with LVEF ≤40% and DELIVER enrolling those with LVEF >40%. Individuals with a previous history of type 2 diabetes or new-onset T2D were included in the analysis. Assessing a combination of worsening heart failure or cardiovascular death was the primary outcome. The study utilized various statistical models to determine time-to-event data and total events. Additionally, changes in patients’ quality of life were measured using the Kansas City Cardiomyopathy Questionnaire (KCCQ) scores, and the results were analyzed.

Findings:

• Out of 11,007 patients enrolled in both trials, 5,274 had T2D at baseline, with 756 of these patients also having a history of neuropathy.
• Patients with neuropathy had more advanced heart failure and worse overall health, as indicated by higher body mass index (BMI), worse kidney function, and longer duration of diabetes.
• They also had higher HbA1c levels, indicating poorer glycemic control, and a longer history of heart failure.
• Patients with neuropathy were found to have higher risks of adverse outcomes such as heart failure hospitalization and cardiovascular death.
• However, after adjusting for other prognostic factors (such as diabetes duration and HbA1c levels), neuropathy was no longer independently associated with these worse outcomes.

Interestingly, the study found that dapagliflozin reduced the risk of heart failure worsening or cardiovascular death to a similar extent in patients with and without neuropathy but the beneficial effects of dapagliflozin on heart failure hospitalizations and cardiovascular death were more in patients with neuropathy compared to those without. This suggests that patients with neuropathy may experience greater absolute benefits from the medication. The number of patients needed to treat to prevent one event was lower in the neuropathy group, making the treatment particularly impactful for these patients. Despite some limitations, treatment with dapagliflozin may provide substantial benefits, particularly for those with neuropathy.

Further reading: Butt JH, Shen L, Inzucchi SE, et al. Dapagliflozin in Heart Failure, Type 2 Diabetes, and Neuropathy: A Meta-Analysis of DAPA-HF and DELIVER. JACC Heart Fail. Published online August 28, 2024. doi:10.1016/j.jchf.2024.07.017