Effects of dapagliflozin on the progression of left ventricular dysfunction in type 2 diabetes mellitus: a randomized controlled trial

Screening for HF may identify asymptomatic abnormalities of LV structure or function, described as stage B heart failure (SBHF) in asymptomatic patients with type 2 diabetes mellitus (T2DM). Sodium-glucose transport protein-2 (SGLT2) inhibitors are associated with reduction of overt HF in T2DM, but the mechanism of their effect in SBHF remains obscure. We sought to assess the response of cardiac function and exercise capacity to dapagliflozin vs placebo in T2DM with stage B HF. The LEAVE-DM (Limiting the progression of Echocardiographically-Assessed left VEntricular dysfunction in Diabetes Mellitus) trial assessed echocardiography and 6-min walk (6MWD) in 262 people with well-controlled T2DM (age 73 ± 7 years; 159 women). Those with LVD (n = 139) were randomized 1:1 to dapagliflozin 10 mg/day or placebo. Follow-up was undertaken at 6 and 24 months and the primary endpoint was global longitudinal strain (GLS). Within the randomized group with LV dysfunction, dapagliflozin was associated with reduction of LA volume index (− 2.0 ± 9.0 vs. 0.03 ± 8.6, p = 0.002), and average E/e′ (− 0.1 ± 2.4 vs. 0.7 ± 2.4, p < 0.001), and improved LA reservoir strain (1.8 ± 4.0 vs. − 0.2 ± 4.0, p = 0.02) from baseline to 6 months follow-up. There was an improvement in exercise capacity on dapagliflozin at 6 months follow-up (Δ6MWD 17 ± 46 vs. 2 ± 73 m, p = 0.001). However, although abnormal GLS (< 16%) was less common at 6 months follow-up (41% vs. 49%, p = 0.03), there was no difference in ΔGLS from baseline to 6 months between dapagliflozin and placebo (p = 0.18). There were no significant differences between 6 and 24 months. Dapagliflozin showed improvements in diastolic function, atrial function and exercise capacity in in patients with T2DM and SBHF, but no change in GLS. Trial Registration: ACTRN12619001393145 at Australia and New Zealand Clinical Trials registry ( https://www.anzctr.org.au/ ).