Introduction

Studies have demonstrated the beneficial effects of sodium-glucose co-transporter-2 (SGLT-2) inhibitors in terms of reverse remodelling in heart failure (HF) patients. Nevertheless, the mechanisms associated with these benefits are not clearly understood. It has been postulated that SGLT-2 inhibitors may exert this beneficial impact by improving the cardiac structure and function. Few pre-clinical studies have suggested that SGLT2 inhibitors may reduce inflammation resulting in beneficial cardiac effect. However, there is a dearth of clinical data with regards to this.

Aim

To determine whether the improvement in cardiac remodelling caused by dapagliflozin in patients with type-2 diabetes mellitus (T2DM) and left ventricular hypertrophy (LVH) is mediated with its anti-inflammatory effect.

Patient Profile

Patients with T2DM, LVH, and without uncontrolled hypertension or symptomatic HF

Methods

Study Design

• A sub-study of the DAPA-LVH study
• DAPA-LVH was a randomized double-blind study.

Treatment Strategy

• Patients were randomized to dapagliflozin 10 mg daily (n=32) or placebo (n=34) for 12 months.

  Assessments

• All the patients underwent cardiac magnetic resonance imaging (CMR) at baseline and at end of the treatment.
• Plasma samples were evaluated to measure C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), interleukin 6 (IL-6), and interleukin 10 (IL-10) and neutrophil-to-lymphocyte ratio (NLR).

Outcomes

• Change in absolute left ventricular mass from baseline.
• Change in various inflammatory markers.

  Results

• The mean age of the study cohort was 65 years, 60% of the study participants were males. The median CRP was 1.07 mg/L and there were no statistically significant between-group differences.
• After 12 months of treatment, patients treated with dapagliflozin vs. those treated with placebo had a significant reduction in CRP (Fig. 1).

Fig. 1: Change in CRP levels at 12 months of treatment

• Treatment with dapagliflozin vs. placebo did not result in any significant changes in the inflammatory markers TNF-α, IL-1β, IL-6, IL-10, ELR, or NLR.
• At the end of 12 months, patients treated with dapagliflozin vs. those treated with placebo had a significant reduction in LV mass and improvement in global longitudinal strain (GLS) (Table 1).

Table 1: Mean change in Cardiac structure parameters at 12 months

• The change in inflammatory mark­ers; NLR (r = 0.311), TNF-α (r = 0.230), and IL-1β (r = 0.246) at 12 months correlated modestly with changes in GLS at 12 months
• As per an analysis stratified based on the baseline CRP, dapagliflozin caused a significant reduction in LV mass regardless of baseline CRP, in individuals with CRP <1.07 mg/L but not in those with CRP ≥ 1.07 mg/L (interaction p value = 0.58) (Table 2).

Table 2: Effect of dapagliflozin on LV mass as per baseline CRP

Conclusions

• In T2DM patients with LVH, treatment with dapagliflozin vs. placebo significantly reduced CRP at 12 weeks.
• Reductions in certain inflammatory markers correlated with improvements in GLS (but not with reduced LV mass).
• The cardiovascular benefits of dapagliflozin might partly be mediated through the reductions in systemic inflammation.

BMC Cardiovasc Disord. 2024 Jul 12;24(1):356.  doi: 10.1186/s12872-024-04022-7.