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Randomized Controlled Trial
. 2024 Oct 22;23(1):373.
doi: 10.1186/s12933-024-02463-0.

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

Soo Lim #  1 , Jae Hyun Bae #  2 , Heran Oh  3 , In-Chang Hwang  4 , Yeonyee E Yoon  4 , Goo-Yeong Cho  4
Affiliations
Randomized Controlled Trial

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

Soo Lim et al. Cardiovasc Diabetol. .

Abstract

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 HbA1c, 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.

Keywords: Angiotensin (1–7); Angiotensin-converting enzyme 2; Diabetes mellitus, type 2; Ertugliflozin; Global longitudinal strain; Heart function tests; Sodium-glucose transporter 2 inhibitors.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
CONSORT diagram showing the trial profile
Fig. 2
Fig. 2
Comparison of changes in echocardiographic parameters between ertugliflozin treatment (n = 48) and placebo (n = 46) for 24 weeks. LAVI, left atrium volume index; LV, left ventricle; LVEDV, left ventricular end-diastolic volume; LVGLS, left ventricular global longitudinal strain. The dashed line represents the median, and the dotted lines indicate the quartiles
Fig. 3
Fig. 3
Comparison of changes in serum NT-proBNP (A), troponin-T (B), ACE2 (C), and angiotensin (1–7) (D) levels after 24 weeks of ertugliflozin treatment (n = 48) or placebo (n = 46). ACE2, angiotensin-converting enzyme 2; NT-proBNP, N-terminal pro–B-type natriuretic peptide. The dashed line represents the median, and the dotted lines indicate the quartiles
See this image and copyright information in PMC

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