Still sour about lactic acidosis years later: role of metformin in heart failure

Kuan, William; Beavers, Craig J.; Guglin, Maya

doi:10.1007/s10741-017-9649-9

Cited by 12 publications

(11 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Historically, metformin should not be used in patients with heart failure due to lactic acidosis risk (21). Nowadays, clinical observations and experimental studies have provided increasing evidence of the safety and benefits of metformin in patients with diabetes and heart failure.…”

Section: Discussionmentioning

confidence: 99%

The Association Between Metformin Treatment and Outcomes in Type 2 Diabetes Mellitus Patients With Heart Failure With Preserved Ejection Fraction: A Retrospective Study

Wang

Lü

Min

et al. 2021

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

Background: Metformin is the first-line antidiabetic medication for type 2 diabetes mellitus (T2DM). However, the association between metformin and outcomes in T2DM patients with heart failure with preserved ejection fraction (HFpEF) is still unknown. We aimed to explore the association between metformin and adverse outcome in T2DM patients with HFpEF.Methods: A total of 372 T2DM patients with HFpEF hospitalized from January 1, 2013, to December 31, 2017, were included in this retrospective cohort study. There were 113 and 259 subjects in metformin and non-metformin group, respectively. Subjects were followed up for all-cause mortality, cardiovascular death, all-cause hospitalization, and heart failure hospitalization.Results: The median follow-up period was 47 months. Eleven patients (2.49% per patient-year) in the metformin group and 56 patients (5.52% per patient-year) in the non-metformin group deceased during follow-up (P = 0.031). However, a multivariable Cox regression failed to show that metformin was an independent factor of all-cause mortality [HR (95% CI) = 0.682 (0.346–1.345); P = 0.269]. A subgroup analysis revealed a significant association between metformin and all-cause mortality in patients with a higher hemoglobin A1c (HbA1c) level (HbA1c ≥7%) [HR (95% CI) = 0.339 (0.117–0.997); P = 0.045]. The 4-year estimated number needed to treat (NNT) with metformin compared with non-metformin for all-cause mortality was 12 in all populations and 8 in the HbA1c ≥7% subgroup.Conclusions: Metformin was not independently associated with clinical outcomes in patients with T2DM and HFpEF, but was associated with lower all-cause mortality in the subgroup of patients with poor glycemic control. Prospective, randomized controlled trials are needed to further verify these findings.

show abstract

Section: Discussionmentioning

confidence: 99%

The Association Between Metformin Treatment and Outcomes in Type 2 Diabetes Mellitus Patients With Heart Failure With Preserved Ejection Fraction: A Retrospective Study

Wang

Lü

Min

et al. 2021

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

show abstract

“…This is linked to a risk of lactic acidosis [95] and therefore, metformin administration can be dangerous in some patients and is usually not recommended for diabetic patients with heart failure [96]. A more recent opinion, however, considers the risk of metformin in diabetic patients with heart failure as minimal and suggests that the cardioprotective benefit outweighs this risk [97]. Indeed, the metabolic and anti-fibrotic effects of metformin on the failing heart have been reviewed, encouraging large-scale clinical trials in diabetic patients with heart failure [98].…”

Section: Metforminmentioning

confidence: 99%

The Role of AMPK Activation for Cardioprotection in Doxorubicin-Induced Cardiotoxicity

Timm

Tyler

2020

Cardiovasc Drugs Ther

126

View full text Add to dashboard Cite

Doxorubicin is a commonly used chemotherapeutic agent for the treatment of a range of cancers, but despite its success in improving cancer survival rates, doxorubicin is cardiotoxic and can lead to congestive heart failure. Therapeutic options for this patient group are limited to standard heart failure medications with the only drug specific for doxorubicin cardiotoxicity to reach FDA approval being dexrazoxane, an iron-chelating agent targeting oxidative stress. However, dexrazoxane has failed to live up to its expectations from preclinical studies while also bringing up concerns about its safety. Despite decades of research, the molecular mechanisms of doxorubicin cardiotoxicity are still poorly understood and oxidative stress is no longer considered to be the sole evil. Mitochondrial impairment, increased apoptosis, dysregulated autophagy and increased fibrosis have also been shown to be crucial players in doxorubicin cardiotoxicity. These cellular processes are all linked by one highly conserved intracellular kinase: adenosine monophosphate-activated protein kinase (AMPK). AMPK regulates mitochondrial biogenesis via PGC1α signalling, increases oxidative mitochondrial metabolism, decreases apoptosis through inhibition of mTOR signalling, increases autophagy through ULK1 and decreases fibrosis through inhibition of TGFβ signalling. AMPK therefore sits at the control point of many mechanisms shown to be involved in doxorubicin cardiotoxicity and cardiac AMPK signalling itself has been shown to be impaired by doxorubicin. In this review, we introduce different agents known to activate AMPK (metformin, statins, resveratrol, thiazolidinediones, AICAR, specific AMPK activators) as well as exercise and dietary restriction, and we discuss the existing evidence for their potential role in cardioprotection from doxorubicin cardiotoxicity.

show abstract

“…Historically, the use of metformin has been restricted in HF owing to concerns regarding the development of life-threatening lactic acidosis [ 43 ]. This adverse side-effect was largely extrapolated from data regarding phenformin, a biguanide that was ultimately withdrawn from the market [ 43 ]. However, the development of metformin-associated lactic acidosis in HF patients has since been refuted.…”

Section: Discussionmentioning

confidence: 99%

Metformin treatment in heart failure with preserved ejection fraction: a systematic review and meta-regression analysis

Halabi

Sen

Huynh

et al. 2020

Cardiovasc Diabetol

View full text Add to dashboard Cite

Background: Observational series suggest a mortality benefit from metformin in the heart failure (HF) population. However, the benefit of metformin in HF with preserved ejection fraction (HFpEF) has yet to be explored. We performed a systematic review and meta-analysis to identify whether variation in EF impacts mortality outcomes in HF patients treated with metformin. Methods: MEDLINE and EMBASE were searched up to October 2019. Observational studies and randomised trials reporting mortality in HF patients and the proportion of patients with an EF > 50% at baseline were included. Other baseline variables were used to assess for heterogeneity in treatment outcomes between groups. Regression models were used to determine the interaction between metformin and subgroups on mortality. Results: Four studies reported the proportion of patients with a preserved EF and were analysed. Metformin reduced mortality in both preserved or reduced EF after adjustment with HF therapies such as angiotensin converting enzyme inhibitors (ACEi) and beta-blockers (β = − 0.2 [95% CI − 0.3 to − 0.1], p = 0.02). Significantly greater protective effects were seen with EF > 50% (p = 0.003). Metformin treatment with insulin, ACEi and beta-blocker therapy were also shown to have a reduction in mortality (insulin p = 0.002; ACEi p < 0.001; beta-blocker p = 0.017), whereas female gender was associated with worse outcomes (p < 0.001). Conclusions: Metformin treatment is associated with a reduction in mortality in patients with HFpEF.

show abstract

Still sour about lactic acidosis years later: role of metformin in heart failure

Cited by 12 publications

References 26 publications

The Association Between Metformin Treatment and Outcomes in Type 2 Diabetes Mellitus Patients With Heart Failure With Preserved Ejection Fraction: A Retrospective Study

The Association Between Metformin Treatment and Outcomes in Type 2 Diabetes Mellitus Patients With Heart Failure With Preserved Ejection Fraction: A Retrospective Study

The Role of AMPK Activation for Cardioprotection in Doxorubicin-Induced Cardiotoxicity

Metformin treatment in heart failure with preserved ejection fraction: a systematic review and meta-regression analysis

Contact Info

Product

Resources

About