Different effects of SGLT2 inhibitors according to the presence and types of heart failure in type 2 diabetic patients

Hwang, Ingyu; Cho, Goo Yeong; Park, Jin Joo; Park, Jun Bean; Lee, Seung–Pyo; Kim, Yong Jin; Sohn, Dae Won

doi:10.1186/s12933-020-01042-3

Cited by 42 publications

(45 citation statements)

References 38 publications

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“…In T2DM patients, the DAPA-LVH trial showed that SGLT2i reversed left ventricular hypertrophy compared to placebo [ 24 ], but the EMPA-HEART CardioLink-6 trial showed nonsignificant results [ 25 ]. The impacts on LVEF [ 25 , 26 ], global longitudinal strain (GLS) [ 24 , 27 ], and diastolic function [ 25 , 28 ] were also inconsistent in different studies. Similarly, in patients with T2DM and HF, the effects of SGLT2i on left ventricular hypertrophy [ 27 , 29 ], cardiac function [ 27 , 30 , 31 ], and neurohormonal parameters [ 32 , 33 ] were inconsistent.…”

Section: Introductionmentioning

confidence: 99%

Effect of sodium–glucose cotransporter 2 inhibitors on cardiac structure and function in type 2 diabetes mellitus patients with or without chronic heart failure: a meta-analysis

Zhao

Wang

et al. 2021

Cardiovasc Diabetol

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Background Although the benefits of sodium–glucose cotransporter 2 inhibitors (SGLT2i) on cardiovascular events have been reported in patients with type 2 diabetes mellitus (T2DM) with or without heart failure (HF), the impact of SGLT2i on cardiac remodelling remains to be established. Methods We searched the PubMed, Embase, Cochrane Library and Web of Science databases up to November 16th, 2020, for randomized controlled trials reporting the effects of SGLT2i on parameters of cardiac structure, cardiac function, plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) level or the Kansas City Cardiomyopathy Questionnaire (KCCQ) score in T2DM patients with or without chronic HF. The effect size was expressed as the mean difference (MD) or standardized mean difference (SMD) and its 95% confidence interval (CI). Subgroup analyses were performed based on the stage A–B or stage C HF population and HF types. Results Compared to placebo or other antidiabetic drugs, SGLT2i showed no significant effects on left ventricular mass index, left ventricular end diastolic volume index, left ventricular end systolic volume index, or left atrial volume index. SGLT2i improved left ventricular ejection fraction only in the subgroup of HF patients with reduced ejection fraction (MD 3.16%, 95% CI 0.11 to 6.22, p = 0.04; I2 = 0%), and did not affect the global longitudinal strain in the overall analysis including stage A–B HF patients. SGLT2i showed benefits in the E/e’ ratio (MD − 0.45, 95% CI − 0.88 to − 0.03, p = 0.04; I2 = 0%), plasma NT-proBNP level (SMD − 0.09, 95% CI − 0.16 to − 0.03, p = 0.004; I2 = 0%), and the KCCQ score (SMD 3.12, 95% CI 0.76 to 5.47, p = 0.01; I2 = 0%) in the overall population. Conclusion The use of SGLT2i was associated with significant improvements in cardiac diastolic function, plasma NT-proBNP level, and the KCCQ score in T2DM patients with or without chronic HF, but did not significantly affect cardiac structural parameters indexed by body surface area. The LVEF level was improved only in HF patients with reduced ejection fraction.

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Section: Introductionmentioning

confidence: 99%

Effect of sodium–glucose cotransporter 2 inhibitors on cardiac structure and function in type 2 diabetes mellitus patients with or without chronic heart failure: a meta-analysis

Zhao

Wang

et al. 2021

Cardiovasc Diabetol

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“…A better understanding of the interplay between diabetes and HF is crucial for the development of new therapies. This has recently been emphasized by the promising results of studies using SGLT-2 inhibitors in diabetic patients with HF [ 34 , 35 ]. The results of ongoing randomized controlled trials using SGLT-2i in HFpEF [ 4 , 20 ] are eagerly awaited.…”

Section: Discussionmentioning

confidence: 99%

Diabetic phenotype and prognosis of patients with heart failure and preserved ejection fraction in a real life cohort

Lejeune

Slimani

Pasquet

et al. 2021

Cardiovasc Diabetol

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Background Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome, with several underlying etiologic and pathophysiologic factors. The presence of diabetes might identify an important phenotype, with implications for therapeutic strategies. While diabetes is associated with worse prognosis in HFpEF, the prognostic impact of glycemic control is yet unknown. Hence, we investigated phenotypic differences between diabetic and non-diabetic HFpEF patients (pts), and the prognostic impact of glycated hemoglobin (HbA1C). Methods We prospectively enrolled 183 pts with HFpEF (78 ± 9 years, 38% men), including 70 (38%) diabetics (type 2 diabetes only). They underwent 2D echocardiography (n = 183), cardiac magnetic resonance (CMR) (n = 150), and were followed for a combined outcome of all-cause mortality and first HF hospitalization. The prognostic impact of diabetes and glycemic control were determined with Cox proportional hazard models, and illustrated by adjusted Kaplan Meier curves. Results Diabetic HFpEF pts were younger (76 ± 9 vs 80 ± 8 years, p = 0.002), more obese (BMI 31 ± 6 vs 27 ± 6 kg/m2, p = 0.001) and suffered more frequently from sleep apnea (18% vs 7%, p = 0.032). Atrial fibrillation, however, was more frequent in non-diabetic pts (69% vs 53%, p = 0.028). Although no echocardiographic difference could be detected, CMR analysis revealed a trend towards higher LV mass (66 ± 18 vs 71 ± 14 g/m2, p = 0.07) and higher levels of fibrosis (53% vs 36% of patients had ECV by T1 mapping > 33%, p = 0.05) in diabetic patients. Over 25 ± 12 months, 111 HFpEF pts (63%) reached the combined outcome (24 deaths and 87 HF hospitalizations). Diabetes was a significant predictor of mortality and hospitalization for heart failure (HR: 1.72 [1.1–2.6], p = 0.011, adjusted for age, BMI, NYHA class and renal function). In diabetic patients, lower levels of glycated hemoglobin (HbA1C < 7%) were associated with worse prognosis (HR: 2.07 [1.1–4.0], p = 0.028 adjusted for age, BMI, hemoglobin and NT-proBNP levels). Conclusion Our study highlights phenotypic features characterizing diabetic patients with HFpEF. Notably, they are younger and more obese than their non-diabetic counterpart, but suffer less from atrial fibrillation. Although diabetes is a predictor of poor outcome in HFpEF, intensive glycemic control (HbA1C < 7%) in diabetic patients is associated with worse prognosis.

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“…Moreover, the augmented glycosuria results in an energy shift to enhanced ketone metabolism and inhibited cardiac sodium-hydrogen exchange. These effects improve myocardial energy metabolism which appears to reduce myocardial inflammation and fibrosis [25]. Whilst there are many possible mechanisms, the exact role of SGLT2 inhibition in ameliorating cardiovascular and heart failure outcomes is unclear.…”

Section: Sglt2 Inhibitors Improve Cardiovascular and Renal Outcomes Imentioning

confidence: 99%

“…The DELIVER trial is a phase III international, multicentre, parallel-group, randomised, Fig. 1 Key potential mechanisms by which SGLT2 inhibitors may improve heart failure and cardiovascular outcomes in people with HFrEF and HFpEF [23][24][25]. SGLT2 sodium-glucose co-transporter 2 double-blind, placebo-controlled study evaluating the impact of dapagliflozin 10 mg versus placebo in participants with HFpEF [33].…”

Section: The Deliver Trial: What Will It Add?mentioning

confidence: 99%

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Dapagliflozin for Heart Failure with Preserved Ejection Fraction: Will the DELIVER Study Deliver?

Williams

Evans

2020

Diabetes Ther

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Drug therapies for people with heart failure and preserved ejection fraction (HFpEF) are often limited to diuretics to improve symptoms as no therapies demonstrate a mortality benefit in this cohort. People with diabetes have a high risk of developing HFpEF and vice versa, suggesting shared pathophysiological mechanisms exist, which in turn engenders the potential for shared treatments. Dapagliflozin is a sodium-glucose co-transporter 2 (SGLT2) inhibitor which has demonstrated significantly improved cardiovascular and hospitalisation for heart failure (HHF) outcomes in previous cardiovascular outcome trials (CVOTs). These CVOTs include the DECLARE-TIMI and DAPA-HF studies which observed significant benefits for people with heart failure and specifically those with heart failure and reduced ejection fraction (HFrEF), respectively. The ongoing DELIVER study is evaluating the use of dapagliflozin specifically in people with HFpEF, which may have enormous implications for treatment and considerable economic consequences. This will complement previous and other ongoing CVOTs evaluating dapagliflozin use. In this review we discuss the use of SGLT2 inhibitors in HFrEF and HFpEF with a focus on the DELIVER study and its potential health and economic implications.

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Different effects of SGLT2 inhibitors according to the presence and types of heart failure in type 2 diabetic patients

Cited by 42 publications

References 38 publications

Effect of sodium–glucose cotransporter 2 inhibitors on cardiac structure and function in type 2 diabetes mellitus patients with or without chronic heart failure: a meta-analysis

Effect of sodium–glucose cotransporter 2 inhibitors on cardiac structure and function in type 2 diabetes mellitus patients with or without chronic heart failure: a meta-analysis

Diabetic phenotype and prognosis of patients with heart failure and preserved ejection fraction in a real life cohort

Dapagliflozin for Heart Failure with Preserved Ejection Fraction: Will the DELIVER Study Deliver?

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