Empagliflozin improves left ventricular diastolic function of db/db mice

Moellmann, Julia; Klinkhammer, Barbara M.; Droste, Patrick; Kappel, B.; Haj-Yehia, Elias; Maxeiner, Sebastian; Artati, Anna; Adamski, Jerzy; Schütt, Katharina; Lopaschuk, Gary D.; Verma, Subodh; Lehrke, Michael

doi:10.1016/j.bbadis.2020.165807

Cited by 44 publications

(47 citation statements)

References 31 publications

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“…Moreover, it has been proven that empagliflozin significantly improved left ventricular diastolic function and reduced mortality in mice, probably by reducing spontaneous diastolic sarcoplasmic reticulum calcium release. Leakage was thought to be the mechanism of diastolic dysfunction ( 27 ). In addition, empagliflozin also promoted cardiac function in non-diabetic rats, which may be associated with improved cardiac metabolism and cardiac ATP production ( 28 ).…”

Section: Discussionmentioning

confidence: 99%

Empagliflozin in Patients With Heart Failure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Pan

Lin

Chen

et al. 2021

Front. Cardiovasc. Med.

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Purpose: The purpose of the study is to evaluate the effect of empagliflozin in patients with heart failure (HF).Method: We performed a systematic search of PubMed, EMBASE, and the Cochrane Library database through January 20, 2021. Randomized controlled trials (RCTs) were included that compared empagliflozin and placebo in patients with HF. Dichotomous variables were expressed as risk ratios (RRs) with 95% confidence intervals (CIs). Continuous variables were calculated and expressed as mean differences (MD) and standard deviation (SD). Meta-analysis was conducted using a random-effects model on outcomes with high heterogeneity.Results: Seven studies were included in our meta-analysis (n = 5,150). Significant differences were observed in a composite of cardiovascular death or hospitalization for worsening heart failure [RR: 0.77 (95% CI 0.68–0.87); I2 = 18%; P < 0.0001), hospitalization for worsening heart failure [RR: 0.71 (95% CI 0.61–0.82); I2 = 0%; P < 0.00001], changes in Kansas City Cardiomyopathy Questionnaire (KCCQ) score [MD: 1.70 (95% CI 1.67–1.73); I2 = 0%; P < 0.00001], and changes in body weight [MD: −1.43 (95% CI −2.15 to −0.72); I2 = 84%; P < 0.0001) from baseline. However, empagliflozin did not show a better change in the 6-min walk test (6MWT) [MD: 34.06 (95% CI −29.75–97.88); I2 = 97%; P = 0.30] or NT-proBNP [MD: −98.36 (95% CI, −225.83–29.11); I2 = 68%; P = 0.13] from baseline.Conclusion: The findings suggest that empagliflozin was effective in reducing a composite of cardiovascular death or hospitalization for worsening heart failure. Further well-designed RCTs are needed to evaluate the long-term effect of empagliflozin in patients with HF.PROSPERO: CRD42021231712.

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Section: Discussionmentioning

confidence: 99%

Empagliflozin in Patients With Heart Failure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Pan

Lin

Chen

et al. 2021

Front. Cardiovasc. Med.

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“…18 The relevant mechanism for induction of cardiac ketone bodycatabolizing enzymes remains obscure and, interestingly, has been detected only in nondiabetic conditions. 56,57 In conclusion, heart failure is a state of metabolic reprogramming that initially can be attributed to adrenergic signaling and in advanced stages leads to energetic deficits. Overlap of the adrenergic-and insulin-signaling pathways suggests similar consequences for adverse cardiac remodeling.…”

Section: Pascal Alexander Mann and Michael Lehrke MDmentioning

confidence: 99%

Cardiac substrate utilization in heart failure: Where is the relevance of SGLT2 inhibition?

Mann

Lehrke

2022

The Journal of Thoracic and Cardiovascular Surgery

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“…We next assessed those biomarkers in another cohort of patients with type 2 diabetes (T2D). In mice and humans including a placebo-controlled trial, we report the impact of sodium glucose cotransporter (SGLT) 2 inhibitor empagliflozin on previously identified glycemic marker 1,5-anhydroglucitol (1,.…”

Section: E T T E R T O E D I T O Rmentioning

confidence: 99%

“…Db/Db mice and Db/+ control mice were fed a high-fat diet ± empagliflozin. 1 Two prospective cohorts for non-targeted metabolomics were recruited: (1) 37 patients with and without T2D hospitalized for myocardial infarction (MI) (Table S1, Figure S1) and (2) 25 patients with T2D included in an empagliflozin registry (Table S2, Figure S2). 2 A targeted analysis of 1,5-AG was performed in a placebo-controlled, randomized, double blind human trial with empagliflozin (n = 42).…”

Section: E T T E R T O E D I T O Rmentioning

confidence: 99%

Human and mouse non‐targeted metabolomics identify 1,5‐anhydroglucitol as SGLT2‐dependent glycemic marker

Kappel

Moellmann

Thiele

et al. 2021

Clinical & Translational Med

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Empagliflozin improves left ventricular diastolic function of db/db mice

Cited by 44 publications

References 31 publications

Empagliflozin in Patients With Heart Failure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Empagliflozin in Patients With Heart Failure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Cardiac substrate utilization in heart failure: Where is the relevance of SGLT2 inhibition?

Human and mouse non‐targeted metabolomics identify 1,5‐anhydroglucitol as SGLT2‐dependent glycemic marker

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