Background and purpose: We aimed to assess the safety, feasibility, and effects on glucose metabolism of treatment with metformin in patients with TIA or minor ischemic stroke and impaired glucose tolerance.
Methods: We performed a multicenter, randomized, controlled, open-label phase II trial with blinded outcome assessment. Patients with TIA or minor ischemic stroke in the previous six months and impaired glucose tolerance (2-hour post-load glucose levels of 7.8-11.0 mmol/l) were randomized to metformin, in a daily dose of 2 g, or no metformin, for three months. Primary outcome measures were safety and feasibility of metformin, and the adjusted difference in 2-hour post-load glucose levels at three months. This trial is registered as an International Standard Randomized Controlled Trial Number 54960762.
Results: Forty patients were enrolled; 19 patients were randomly assigned metformin. Nine patients in the metformin group had side effects, mostly gastrointestinal, leading to permanent discontinuation in four patients after 3-10 weeks. Treatment with metformin was associated with a significant reduction in 2-hour post-load glucose levels of 0·97 mmol/l (95% CI 0·11-1·83) in the on-treatment analysis, but not in the intention-to-treat analysis (0·71 mmol/l; 95% CI -0·36 to 1·78).
Conclusions: Treatment with metformin in patients with TIA or minor ischemic stroke and impaired glucose tolerance is safe, but leads to minor side effects. If tolerated, it may lead to a significant reduction in post-load glucose levels. This suggests that the role of metformin as potential therapeutic agent for secondary stroke prevention should be further explored.
Keywords: TIA; antidiabetics; impaired glucose tolerance; ischemic stroke; metformin; secondary stroke prevention.
© 2013 The Authors. International Journal of Stroke © 2013 World Stroke Organization.