Journal Article

Effect of ertugliflozin on left ventricular function in type 2 diabetes and pre-heart failure: the Ertu-GLS randomized clinical trial

Cho, Goo-Yeong, Yoon, Yeonyee E., Hwang, In-Chang, Lim, Soo, Oh, Heran, Bae, Jae Hyun

2024

Overview

Background The therapeutic effects of ertugliflozin, a sodium-glucose cotransporter 2 inhibitor, on cardiovascular outcome are not fully understood. This study aimed to evaluate the efficacy and safety of ertugliflozin on cardiac function in people with type 2 diabetes and pre-heart failure. Methods We conducted a 24-week randomized, double-blind, placebo-controlled trial involving individuals with type 2 diabetes inadequately controlled with antidiabetic medications. Participants with left ventricular hypertrophy, E/e’ >15, or impaired left ventricular global longitudinal strain (LVGLS) were randomized 1:1 to receive either ertugliflozin (5 mg once daily) or a placebo. The primary outcome was the change in LVGLS. Secondary outcomes included changes in left ventricular mass index (LVMI) and left ventricular ejection fraction (LVEF). Prespecified exploratory outcomes, including angiotensin-converting enzyme 2 (ACE2) and angiotensin (1–7) levels, were also assessed. Results A total of 102 individuals (mean age, 63.9 ± 9.2 years; 38% women) were included. The ertugliflozin group showed a significant improvement in LVGLS (− 15.5 ± 3.1% to − 16.6 ± 2.8%, P  = 0.004) compared to the placebo group (− 16.7 ± 2.7% to − 16.4 ± 2.6%, P  = 0.509), with a significant between-group difference ( P  = 0.013). Improvements in LVMI and LVEF were also observed. Additionally, significant reductions in HbA 1c , systolic blood pressure, whole-body and visceral fat, uric acid, proteinuria, N-terminal pro–B-type natriuretic peptide, and lipoprotein(a) were noted. ACE2 and angiotensin (1–7) levels significantly increased in the ertugliflozin group compared to the placebo group and correlated with changes in LVGLS [ r  = 0.456, P  < 0.001 for ACE2; r  = 0.541, P  < 0.001 for angiotensin (1–7)]. Adverse events were similar between the two groups. Conclusions This study demonstrated that ertugliflozin has beneficial effects on left ventricular function in individuals with type 2 diabetes and pre-heart failure, and it provided insights into potential underlying mechanisms. Clinical trial registration ClinicalTrials.gov Identifier: NCT03717194.

• Publisher: BioMed Central,Springer Nature B.V,BMC
• Subject: ACE2 / Aged / Angiology / Angiotensin / Angiotensin (1–7) / Angiotensin-converting enzyme 2 / Angiotensin-Converting Enzyme 2 - metabolism / Antidiabetics / Biomarkers - blood / Blood Glucose - drug effects / Blood Glucose - metabolism / Blood pressure / Brain natriuretic peptide / Bridged Bicyclo Compounds, Heterocyclic - adverse effects / Bridged Bicyclo Compounds, Heterocyclic - therapeutic use / Cardiac function / Cardiology / Clinical trials / Congestive heart failure / Diabetes / Diabetes mellitus (non-insulin dependent) / Diabetes mellitus, type 2 / Diabetes Mellitus, Type 2 - blood / Diabetes Mellitus, Type 2 - complications / Diabetes Mellitus, Type 2 - diagnosis / Diabetes Mellitus, Type 2 - drug therapy / Diabetes Mellitus, Type 2 - physiopathology / Doppler effect / Double-Blind Method / Ejection fraction / Ertugliflozin / Female / Global longitudinal strain / Glucose / Heart failure / Heart Failure - diagnosis / Heart Failure - drug therapy / Heart Failure - physiopathology / Heart function tests / Humans / Hypertrophy / Hypertrophy, Left Ventricular - diagnostic imaging / Hypertrophy, Left Ventricular - drug therapy / Hypertrophy, Left Ventricular - physiopathology / Male / Medicine / Medicine & Public Health / Middle Aged / Peptides / Peptidyl-dipeptidase A / Placebos / Proteinuria / Recovery of Function / Sodium-glucose cotransporter / Sodium-Glucose Transporter 2 Inhibitors - adverse effects / Sodium-Glucose Transporter 2 Inhibitors - therapeutic use / Stroke Volume - drug effects / Time Factors / Treatment Outcome / Uric acid / Ventricle / Ventricular Dysfunction, Left - diagnosis / Ventricular Dysfunction, Left - drug therapy / Ventricular Dysfunction, Left - physiopathology / Ventricular Function, Left - drug effects