SGLT-2 Inhibition Does Not Improve Left Ventricular Reverse Remodeling in Patients with Diabetes Mellitus Type 2

Abstract

Background SGLT-2 inhibition reduces preload as well as afterload, arterial stiffness and systemic blood pressure thereby improving subendocardial blood flow in patients with heart failure (HF). These beneficial cardiovascular (CV) effects likely lower the risk of death and HF hospitalization. There is no known association between diastolic function parameters as determined by transthoracic echocardiography (TTE) and SGLT-2 inhibitor therapy. We hypothesized that in patients with diabetes mellitus type 2 (DMT2) the use of SGLT-2 inhibitors might improve TTE diastolic function parameters including left ventricular (LV) mass and LV mass index. We aimed to investigate the association between LV mass and LV mass index in patients with DMT2 before and after treatment with SGLT-2 inhibitors beyond 1 year. Methods A retrospective chart review analysis of 141 patients who were prescribed SGLT-2 inhibitors either in the inpatient or outpatient settings at BronxCare Hospital Center between March 1, 2013 through March 31, 2018, was conducted. TTE variables including left atrial volume index (LAVI), LV mass, LV mass index (LVMI) and tricuspid regurgitant (TR) velocity were evaluated before and after prescribing SGLT-2 inhibition. These parameters were compared at baseline and beyond 1 year after treatment. Paired-t testing was used to examine the effect of SGLT-2 inhibition on changes in TTE parameters after 1-year post-treatment. The primary outcome was to detect the change in LV mass and LV mass index. The secondary outcome measures included all-cause and HF admissions. Results Of the 1096 patients on SGLT-2 inhibitors, 361 patients had both pre and post treatment TTE done out of which 141 had TTE beyond1 year of treatment. The mean age of our population was 62 (±10.0) years out of which 61% were female. 60.8% of our populations were Hispanic. In the analysis, we observed that there was an increase in LV mass from 185.9 g to 201.3 g (p=0.002) and LV mass index from 94.5 to 101.7 (p=0.007) in subjects treated with SGLT-2 inhibitors beyond 1 year. We did not observe improvement in any other diastolic TTE parameters such as E/A ratio, RVSP and LAVI with the use of SGLT-2 inhibitors. However, there was no association between all-cause and HF admission as well as total mortality in subjects on SGLT-2 inhibitors (p>0.0999) Conclusion Although SGLT-2 inhibitors have shown in the metabolic model to improve heart failure in diabetic patients, they did not show a potential role in the improvement of LV reverse remodeling. On the contrary, our data suggests a modest increase in LV mass and LVMI in patients with T2DM taking SGLT-2 inhibitors. Future studies with larger population size over an extended period of time are warranted to validate our results.