Narrative review explores metformin and trimetazidine in cardiovascular conditions

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Frontiers in Medicine Published April 18, 2026 Medically reviewed April 25, 2026 DOI ↗ By Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease

Key Takeaway

Note that this narrative review lacks reported safety data and specific outcomes for metformin and trimetazidine in cardiovascular disease.

This narrative review focuses on the potential applications of metformin and trimetazidine across a range of cardiovascular conditions, including atherosclerosis, vascular calcification, heart failure, ischemia-reperfusion injury, and arrhythmias. The scope of the publication encompasses these specific disease states but does not provide details on the underlying studies, such as sample sizes or specific intervention protocols.

The authors discuss the theoretical or observed associations between these medications and cardiovascular health. However, the review does not report specific primary or secondary outcomes, nor does it provide pooled effect sizes or confidence intervals. Consequently, the synthesized arguments rely on qualitative conclusions rather than quantitative meta-analytic data.

Significant limitations are inherent to this source. Key details such as the study population, setting, follow-up duration, and adverse events were not reported in the provided information. The absence of data on tolerability, discontinuations, or serious adverse events prevents a comprehensive safety assessment. Furthermore, the review does not explicitly address funding sources or potential conflicts of interest.

Due to the lack of reported practice relevance and the narrative nature of the source, clinicians should interpret these findings with restraint. The review does not establish causal links or provide definitive guidance for immediate clinical decision-making regarding metformin or trimetazidine in these specific cardiovascular contexts.

Study Details

Study typeSystematic review

EvidenceLevel 1

PublishedApr 2026

View Original Abstract ↓

Cardiovascular diseases (CVDs) remain a leading global health burden, necessitating novel insights into their pathogenesis and therapeutic strategies. Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has emerged as a pivotal mechanism in CVD progression. This review comprehensively synthesizes current knowledge on the molecular drivers of ferroptosis, including dysregulated iron metabolism, glutathione peroxidase 4 (GPX4) inactivation, and redox imbalance orchestrated by Nrf2, AMPK, and p53. Subcellular organelles such as mitochondria, lysosomes, and the endoplasmic reticulum are highlighted as critical hubs for initiating or amplifying ferroptotic signals through oxidative stress, metabolic dysfunction, and organelle-specific interactions. The role of ferroptosis in major cardiovascular pathologies—atherosclerosis, vascular calcification, heart failure, ischemia-reperfusion injury, and arrhythmias—is systematically explored, emphasizing its contribution to cellular damage, inflammation, and tissue remodeling. Notably, this review incorporates discussions on spatial metabolomics as a powerful analytical tool, highlighting its unique capacity to decipher region-specific metabolic alterations and spatial distribution patterns of key molecules involved in ferroptosis, thereby providing deeper insights into the spatiotemporal dynamics of ferroptotic mechanisms in CVDs. Furthermore, emerging therapeutic strategies targeting ferroptosis, including iron chelators, lipid peroxidation inhibitors, and metabolic modulators (e.g., metformin, trimetazidine), are discussed for their potential to mitigate cardiovascular damage. By bridging molecular mechanisms (enhanced by spatial metabolomics insights) to clinical applications, this review underscores ferroptosis as a promising therapeutic target, advocating for further research to translate these insights into precision interventions for CVD management.