Metformin reduces aneurysm wall enhancement on high-resolution vessel wall MRI in unruptured vertebrobasilar dissecting aneurysms: a randomized controlled clinical trial

Background Vertebrobasilar dissecting aneurysms (VBDAs) are an important cause of ischemic stroke in young and middle-aged adults. High-resolution vessel wall imaging (HR-VWI) enables non-invasive assessment of aneurysm wall inflammation. Metformin has anti-inflammatory properties, but its potential role in unruptured VBDAs remains unclear. We evaluated the effect of 6 months of metformin therapy on aneurysm wall enhancement in unruptured VBDAs. Methods In this multicenter, prospective, randomized, double-blind, placebo-controlled trial, patients with unruptured VBDAs showing wall enhancement on HR-VWI between May 2024 and September 2025 were assigned 1:1 to receive metformin 250 mg twice daily or placebo for 6 months. The co-primary outcomes were changes in wall enhancement volume ratio (WEVR) and wall enhancement index (WEI) from baseline to 6 months. Secondary outcomes included changes in total outer aneurysm diameter, luminal diameter, intramural hematoma volume (IHV), and circulating inflammatory biomarkers. Results A total of 60 patients were included in the final analysis (30 per group). After 6 months, reductions in WEVR and WEI were significantly greater in the metformin group than in the placebo group (ΔWEVR: −8.91% vs 6.71%, P<0.001; ΔWEI: −0.16 vs 0.09, P<0.001). In patients with intramural hematoma, the increase in IHV was significantly smaller in the metformin group (ΔIHV: 145.60 mm³ vs 245.30 mm³, P=0.025). Additionally, C-reactive protein, tumor necrosis factor α, and interleukin 1β levels showed significantly greater reductions with metformin than with placebo (P<0.05). Conclusion Metformin significantly reduced aneurysm wall enhancement in patients with unruptured VBDAs, was associated with less progression of intramural hematoma, and reduced selected circulating inflammatory biomarker levels. Trial registration number NCT06405971.