Impact of dapagliflozin on left ventricular diastolic function of patients with type 2 diabetic mellitus with chronic heart failure

Abstract

BackgroundThe objective of this study was to investigate the impact of sodium glucose cotransporter type 2 (SGLT2) inhibitors on left ventricular (LV) diastolic function of type 2 diabetes mellitus (T2DM) patients with heart failure (HF).MethodsThis trial was a prospective multicenter study of 58 T2DM patients with stable HF at five institutions in Japan. Patients who had been taking at least one antidiabetic drugs other than SGLT2 inhibitors started the administration of 5 mg/day of dapagliflozin. The physical examinations, blood tests, and echocardiography were performed at baseline and 6 months after administration of dapagliflozin. The primary endpoint was defined as a change in mitral inflow E and mitral e′ annular velocities (E/e′) between baseline and 6 months after the administration of dapagliflozin. The secondary end points consisted of a change in brain natriuretic peptide (BNP), LV mass index (LVMI) and left atrial volume index (LAVI).ResultsE/e′ significantly decreased from 9.3 to 8.5 cm/s (p = 0.020) 6 months after administration of dapagliflozin. LAVI and LVMI significantly decreased from 31 to 26 mL/m2 (p = 0.001), and from 75.0 to 67.0 g/m2 (p < 0.001), respectively, 6 months after administration of dapagliflozin. No significant change was observed in BNP (from 27.9 to 28.9 pg/mL; p = 0.132) 6 months after administration of dapagliflozin, except for a significant decrease from 168.8 to 114.3 pg/mL (p = 0.012) in patients with BNP ≥ 100 pg/mL.ConclusionThis prospective multicenter trial showed the beneficial effect of SGLT2 inhibitors on LV diastolic functional parameters for T2DM patients with HF. Our findings may thus offer a new insight into the management of T2DM patients.Trial registration UMIN000019789, Registered 28 September 2014, Date of registration: 11/14/2015, Date of enrolment of the first participant to the trial: 6/15/2016, Date of enrolment of the last participant to the trial: 12/9/2017

Effect of tofogliflozin on cardiac and vascular endothelial function in patients with type 2 diabetes and heart diseases: A pilot study

“…A recent report showed that patients with E/e ′ of diabetes and HF were improved by SGLT2 inhibitor. However, the mechanism is still unclear.…”

Reappraisal on pharmacological and mechanical treatments of heart failure

“…In patients with T2DM who had or were at risk for atherosclerotic cardiovascular disease, treatment with dapagliflozin robustly resulted in a lower rate of cardiovascular death or HHF [125,126], and subgroup analysis showed that dapagliflozin reduced HHF in patients with and without HFrEF [127]. Another prospective multicentre trial showed the beneficial effect of dapagliflozin on LV diastolic functional parameters for T2DM patients with HF [128]. CREDENCE and CANVAS supported that canagliflozin significantly reduced major cardiovascular events in patients with T2DM and cardiovascular disease [129][130][131].…”

“…VNS NECTAR-HF [92,93], ANTHEM-HF [94,95] Comorbidities T2DM SGLT-2i: Empagliflozin EMPA-REG OUTCOME [112,114,122], EMPRISE [124]; Dapagliflozin: DECLARE-TIMI 58 [117,[125][126][127], Soga et al [128]; DAPA-HF [118,119]; Canagliflozin: CANVAS [120,131,132], CREDENCE [129,130]. GLP-1: Liraglutide: LEADER [141], LIVE [142], and FIGHT [143]; Semaglutide: SUSTAIN-6 [144] DPP4i: Sitagliptin: TECOS [146,147]; Saxagliptin: SAVOR-TIMI 53 [148]; Vildagliptin: VIVIDD [149]; Linagliptin: CARMELINA [150];…”

Evaluation of the effects of sodium–glucose co‐transporter 2 inhibition with empagliflozin on morbidity and mortality in patients with chronic heart failure and a preserved ejection fraction: rationale for and design of the EMPEROR‐Preserved Trial

“…14 In clinical trials, the use of SGLT2 inhibitors has been shown to reduce the quantity of epicardial adipose tissue (independently of effect on body weight), [35][36][37] and these drugs ameliorate the inflammation of adipose tissue surrounding the heart and great vessels 38,39 and the associated abnormalities of cardiac filling and aortic distensibility in both experimental and clinical HFpEF. 18,[40][41][42] Furthermore, SGLT2 inhibitors act to inhibit sodium reabsorption in the proximal renal tubules, in which the majority of renal sodium retention occurs [43][44][45] ; this action explains the marked reduction in plasma and/or interstitial volume and haemoconcentration seen in randomized controlled trials in type 2 diabetes. 25,46 Moreover, SGLT2 inhibitors can attenuate renal inflammation and fibrosis.…”