Dapagliflozin offers cardioprotection in HF patients with T2D

Treatment with dapagliflozin results in a lower risk of worsening heart failure (HF) or cardiovascular death and improvements in symptoms among patients with HF and type 2 diabetes (T2D), with or without neuropathy, according to a study presented at AHA 2023. However, the beneficial effects of dapagliflozin appears more evident in those with neuropathy.

Moreover, the study demonstrates a favourable safety profile and tolerability, regardless of patient’s neuropathy status.

“T2D is a common comorbidity in HF, and neuropathy is a serious complication in patients with T2D that is associated with worse outcomes,” according to the researchers, led by Dr Jawad Haider Butt from Department of Cardiology, Rigshospitalet, Copenhagen, Denmark.

Butt and his team performed a patient-level pooled analysis of the DAPA-HF and DELIVER trials to assess the efficacy and safety of dapagliflozin compared with placebo according to neuropathy status in patients with T2D and HF with reduced ejection fraction (HFrEF) and HF with mid-range EF (HFmrEF) or HF with preserved EF (HFpEF).

A composite of worsening HF or cardiovascular death served as the primary outcome. In total, 5,274 patients with T2D at baseline were included in the analysis. Of these, 756 (14.3 percent) had a history of neuropathy. [AHA 2023, abstract 2181]

Patients with neuropathy were more likely to be female and have a history of hypertension and peripheral arterial disease (PAD) compared with those without neuropathy. They also had a higher body mass index, glycated haemoglobin, and left ventricular ejection fraction and a lower estimated glomerular filtration rate and N-terminal prohormone of brain natriuretic peptide.

Notably, the duration of both T2D and HF were much longer in patients with neuropathy. They also demonstrated worse NYHA functional class and KCCQ scores, as well as higher rates of all outcomes.

The beneficial effects of dapagliflozin on the primary outcome persisted regardless of the patient’s neuropathy status (p_interaction=0.11): with neuropathy (hazard ratio [HR], 0.63, 95 percent confidence interval [CI], 0.46‒0.84) and without neuropathy (HR, 0.81, 95 percent CI, 0.72‒0.92).

Neuropathy status

Additionally, treatment with dapagliflozin reduced the risk of other outcomes (eg, HF hospitalization, myocardial infarction, stroke) and improved the mean KCCQ scores from baseline to 8 months in patients with and without neuropathy. Interestingly, the effects of the study drug appeared greater among those with neuropathy.

Incidence of adverse events and treatment discontinuation were not higher with dapagliflozin relative to that with placebo, regardless of neuropathy status, indicating its safety and tolerability.

“Dapagliflozin reduced the risk of worsening HF or cardiovascular death and improved symptoms in patients with HF and T2D, with and without neuropathy, possibly with larger effects in individuals with neuropathy,” the researchers said. “In addition, dapagliflozin was safe and well-tolerated, irrespective of neuropathy status.”

These findings were consistent with those of a 2021 meta-analysis of randomized controlled trials. In this study, dapagliflozin reduced the rate of HF hospitalization, cardiovascular death, and all-cause mortality in patients with HFrEF and T2D. However, it showed no significant protective effect in those with HFpEF. [Front Clin Diabetes Healthc 2021:2:703937]