Abstract
BACKGROUND: Metformin, a widely prescribed glucose-lowering agent, has demonstrated cardiovascular benefits in patients with diabetes who do not have established atherosclerotic cardiovascular disease. However, evidence regarding its role specifically in patients with diabetes undergoing percutaneous coronary intervention (PCI) remains limited. This study therefore aimed to evaluate the prognostic association of metformin use in this high‑risk population and to explore its potential interaction with procedural complexity. METHODS: From January 2017 to December 2018, 11,585 diabetic patients undergoing PCI at Fuwai hospital were consecutively enrolled in our study. Patients were categorized into four groups according to metformin use and PCI complexity. The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCEs), including cardiovascular death, non-fatal myocardial infarction (MI), non-fatal stroke, and unplanned revascularization. RESULTS: After a follow-up of 3 years, a total of 1292 MACCEs were recorded. Overall, metformin use was observed to be associated with a lower incidence of 3-year MACCEs (adjusted HR 0.80, 95%CI 0.70–0.92) after multivariable adjustment. Significantly lower incidence of MACCEs was observed in patients undergoing non-complex PCI (adjusted HR 0.65, 95% CI: 0.53–0.79), while such protective effect of metformin didn’t exist in complex PCI patients (adjusted HR 1.00, 95%CI: 0.83–1.21). Significant interaction between metformin and PCI complexity was found with regard to the 3-year MACCE rate (P(interaction) = 0.003; adjusted P(interaction) = 0.002). CONCLUSIONS: In this observational study, there was significant difference in the efficacy of metformin in diabetic patients undergoing complex or non-complex PCI. Metformin use was associated with improved prognosis in patients with diabetes undergoing non-complex PCI. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12933-026-03102-6.