Dapagliflozin Regresses Left Ventricular Hypertrophy in People with Type 2 Diabetes

  • Alexander Brown

Student thesis: Doctoral ThesisDoctor of Medicine

Abstract

People with Type 2 diabetes (T2D) have a two to fourfold increased risk of cardiovascular mortality. Sodium–glucose cotransporter 2 inhibitors (SGLT2i) have been shown to reduce cardiovascular events, particularly heart failure, in cardiovascular outcome trials. One potential mechanism that may explain this benefit is regression of left ventricular hypertrophy (LVH); an independent predictor of cardiovascular events including incident heart failure.

We tested the hypothesis that dapagliflozin may regress LVH in people with T2D.

We randomly assigned 66 people (mean age 67 +/- 7 years, 38 males) with T2D, LVH and controlled blood pressure to receive dapagliflozin 10mg once-daily or placebo for 12 months. Primary endpoint was change in absolute left ventricular mass (LVM), assessed by cardiac magnetic resonance imaging.

In the intention to treat analysis, dapagliflozin significantly reduced LVM compared to placebo with an absolute mean change of -2.82g (95% confidence interval (CI): -5.13 to -0.51, p= 0.018). Additional sensitivity analysis adjusting for baseline LVM, blood pressure, weight and angiotensin converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) prescription showed the LVM change to remain statistically significant (mean change -2.87g (95% CI: -5.27 to -0.48, p=0.02)). Dapagliflozin induced LVM regression was greatest in those with above-median left ventricular mass indexed (LVMI) to body surface area (BSA) at baseline (mean change -3.88g (95% CI: -7.33 to -0.43, p=0.029)). Dapagliflozin significantly improved pre-specified secondary end points including ambulatory 24 hour systolic blood pressure -3.6 mmHg (95% CI: -6.4 to -0.8; p=0.012), nocturnal systolic blood pressure -4.4mmHg (95% CI: to – 7.9 to -0.8; p=0.017), body weight -3.8 kg (95% CI: -4.9 to 2.6 p<0.001), visceral adipose tissue (VAT) -679.4 cm3 (95% CI: -998.0 to -360.8, p<0.001), subcutaneous adipose tissue (SCAT) -609.8cm3 (95% CI: -948.1 to -271.3 p=0.001), insulin resistance, HOMA-IR -2.6 (95% CI: -4.5 to -0.7, p=0.017), and high-sensitivity c-reactive protein (hsCRP) -1296.0 ng/l (95% CI: -2650.6 to -31.5, p=0.049).

Dapagliflozin treatment reduced LVM in people with T2D and LVH. This reduction in LVM was accompanied by reductions in systolic blood pressure, body weight, visceral and subcutaneous adipose tissue, insulin resistance and hsCRP. The regression of LVM suggests dapagliflozin can initiate reverse remodelling and changes in left ventricular structure which may be an important mechanism of action for the cardioprotective effects of SGLT2i.
Date of Award2020
Original languageEnglish
SupervisorChim Lang (Supervisor), Allan Struthers (Supervisor) & Rory McCrimmon (Supervisor)

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