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 impairedglucose 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.
RCT Entities:
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.
Authors: Elizabeth Osei; Adrienne Zandbergen; Paul J A M Brouwers; Laus J M M Mulder; Peter Koudstaal; Hester Lingsma; Diederik W J Dippel; Heleen den Hertog Journal: BMJ Open Date: 2021-09-16 Impact factor: 2.692
Authors: Elizabeth Osei; Susanne Fonville; Adrienne A M Zandbergen; Paul J A M Brouwers; Laus J M M Mulder; Hester F Lingsma; Diederik W J Dippel; Peter J Koudstaal; Heleen M den Hertog Journal: Trials Date: 2015-08-05 Impact factor: 2.279