Metformin treatment is associated with improved outcome in patients with diabetes and advanced heart failure (HFrEF)

Beneš, Jan; Kotrč, Martin; Kroupova, Katerina; Wohlfahrt, Peter; Kovář, J.; Franeková, Janka; Hegarová, Markéta; Hošková, Lenka; Hoskova, Eva; Pelikánová, Terezie; Jarolím, Petr; Kautzner, Josef; Melenovský, Vojtěch

doi:10.1038/s41598-022-17327-4

Cited by 18 publications

(10 citation statements)

References 51 publications

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“…There was a trend of additional bene t in patients with LVEF ≤40%, but the difference was not statistically signi cant. This result is in line with another recent study, which showed that metformin was associated with improved outcomes in patients with HFrEF and diabetes [31]. Although the study population was small, this study also found that metformin-treated patients with HF had better glycemic pro les and improved survival compared with those who did not use metformin.…”

Section: Metformin Treatment In Heart Failuresupporting

confidence: 91%

Impact of metformin on the all-cause mortality of diabetic patients hospitalized with acute heart failure: An observational study using acute heart failure registry data

Park

et al. 2023

Preprint

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Background Although the hypothesis that metformin is beneficial for patients with diabetes and heart failure (HF) has been steadily raised, there is limited data on metformin use in patients with acute HF. We investigated the impact of metformin on all-cause mortality in hospitalized patients with type 2 diabetes and acute HF. Methods The Korean Acute Heart Failure registry enrolled patients hospitalized for acute HF from 2011 to 2014. Among this cohort, we analyzed patients with diabetes with baseline estimated glomerular filtration rate (eGFR) of 30 ml/min/1.73m2 or more. We retrospectively investigated the all-cause mortality at 1 year after discharge. Inverse probability treatment weighting method was used to adjust baseline differences on metformin treatment. Results The study analyzed data from 1,309 patients with diabetes (mean age 69 years, 56% male). Among them, 613 (47%) patients were on metformin. During the median follow-up period of 11 months, 132 (19%) and 74 (12%) patients not receiving and receiving metformin treatment died, respectively. The all-cause mortality rate was lower in metformin users than in non-users (hazard ratio 0.616 [0.464–0.819], P < 0.001). HF readmission rate was not significantly different. After adjustment, metformin was significantly associated with a lower risk for all-cause mortality (hazard ratio 0.677 [0.495–0.928], P-value = 0.015). In subgroup analyses, this association remains significant irrespective of baseline kidney function (eGFR < 60 or ≥ 60 ml/min/1.73m2, P-for-interaction = 0.176) or left ventricular ejection fraction (< 40%, 40–49%, or ≥ 50%, P-for-interaction = 0.224). Conclusions Metformin treatment at the time of admission was associated with a lower risk for 1-year all-cause mortality in patients with diabetes, hospitalized for acute HF.

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Section: Metformin Treatment In Heart Failuresupporting

confidence: 91%

Impact of metformin on the all-cause mortality of diabetic patients hospitalized with acute heart failure: An observational study using acute heart failure registry data

Park

et al. 2023

Preprint

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“…Notably, when stratified by LV ejection fraction (LVEF), this relationship was strictly driven by risk reduction among patients with LVEF >40% [53]. On the other hand, a prospective cohort study by Benes et al [54] following 380 patients with diabetes and HF with reduced ejection fraction over an average of 3 years reported improved outcomes with metformin use. The authors found that diabetic patients on metformin demonstrated signs of more stable HF, including lower brain natriuretic peptide levels, lower mitral and tricuspid regurgitation severity, improved LV and right ventricular function, and usage of smaller doses of diuretics.…”

Section: Efficacy In Myocardial Injury and Hfmentioning

confidence: 99%

“…On subgroup analysis, the authors discovered improved outcomes regardless of HF severity or treatment. Furthermore, metformin treatment remained associated with improved outcomes even after adjustment for BMI, brain natriuretic peptide, and renal function, or after propensity score matching utilizing 81 pairs of patients [54].…”

Section: Clinical Studies: Latest Advancesmentioning

confidence: 99%

Cardiovascular Protection by Metformin: Latest Advances in Basic and Clinical Research

Li¹,

Li²

2023

Cardiology

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Background: Metformin is among the most frequently prescribed antidiabetic drugs worldwide and remains the first-line therapy for type 2 diabetes due to its well-established glucose-lowering efficacy and favorable safety profile. Summary: Studies over the past decades show that metformin also exerts many other beneficial effects independent of its glucose-lowering effect both in experimental models and human subjects. Among them, the most notable is its cardiovascular protective effect. In this review, we discuss the latest cutting-edge research findings on metformin’s cardiovascular protection from both preclinical studies and randomized clinical trials. We focus on describing novel basic research discoveries reported in influential journals and discussing their implications in the context of latest clinical trial findings related to common cardiovascular and metabolic disorders, including atherosclerosis and dyslipidemia, myocardial injury, and heart failure. Key Messages: While substantial preclinical and clinical evidence suggests metformin as a potential cardiovascular protectant, large-scale randomized controlled trials are warranted to establish its clinical efficacy in treating patients with atherosclerotic cardiovascular disease and heart failure.

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“…Of note, there was a non-significant 9% reduction in mortality in those with severe left ventricular dysfunction (HR, 0.91 (95% CI: 0.72-1.14)) [70]. A recent propensity score-matched observational study in 847 T2D patients with advanced HFrEF reported markedly lower B-type natriuretic peptide (BNP) levels, improved LVEF, and better event-free survival in metformin users than in controls irrespective of glycemic control [71]. However, these results should be interpreted cautiously, since metformin is often avoided in patients with multiple comorbidities, including HF and their comparators, such as sulfonylurea or SLT2 inhibitors, which may alter the estimated risk of HF.…”

Section: Metforminmentioning

confidence: 99%

Anti-Diabetic Therapy and Heart Failure: Recent Advances in Clinical Evidence and Molecular Mechanism

Hsu

Hsuan

Liao

et al. 2023

Life

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Diabetic patients have a two- to four-fold increase in the risk of heart failure (HF), and the co-existence of diabetes and HF is associated with poor prognosis. In randomized clinical trials (RCTs), compelling evidence has demonstrated the beneficial effects of sodium-glucose co-transporter-2 inhibitors on HF. The mechanism includes increased glucosuria, restored tubular glomerular feedback with attenuated renin–angiotensin II–aldosterone activation, improved energy utilization, decreased sympathetic tone, improved mitochondria calcium homeostasis, enhanced autophagy, and reduced cardiac inflammation, oxidative stress, and fibrosis. The RCTs demonstrated a neutral effect of the glucagon-like peptide receptor agonist on HF despite its weight-reducing effect, probably due to it possibly increasing the heart rate via increasing cyclic adenosine monophosphate (cAMP). Observational studies supported the markedly beneficial effects of bariatric and metabolic surgery on HF despite no current supporting evidence from RCTs. Bromocriptine can be used to treat peripartum cardiomyopathy by reducing the harmful cleaved prolactin fragments during late pregnancy. Preclinical studies suggest the possible beneficial effect of imeglimin on HF through improving mitochondrial function, but further clinical evidence is needed. Although abundant preclinical and observational studies support the beneficial effects of metformin on HF, there is limited evidence from RCTs. Thiazolidinediones increase the risk of hospitalized HF through increasing renal tubular sodium reabsorption mediated via both the genomic and non-genomic action of PPARγ. RCTs suggest that dipeptidyl peptidase-4 inhibitors, including saxagliptin and possibly alogliptin, may increase the risk of hospitalized HF, probably owing to increased circulating vasoactive peptides, which impair endothelial function, activate sympathetic tones, and cause cardiac remodeling. Observational studies and RCTs have demonstrated the neutral effects of insulin, sulfonylureas, an alpha-glucosidase inhibitor, and lifestyle interventions on HF in diabetic patients.

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Metformin treatment is associated with improved outcome in patients with diabetes and advanced heart failure (HFrEF)

Cited by 18 publications

References 51 publications

Impact of metformin on the all-cause mortality of diabetic patients hospitalized with acute heart failure: An observational study using acute heart failure registry data

Impact of metformin on the all-cause mortality of diabetic patients hospitalized with acute heart failure: An observational study using acute heart failure registry data

Cardiovascular Protection by Metformin: Latest Advances in Basic and Clinical Research

Anti-Diabetic Therapy and Heart Failure: Recent Advances in Clinical Evidence and Molecular Mechanism

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