LIMIT: Lowering the Incidence of vascular complications with Metformin in patients with Impaired glucose tolerance and a recent TIA or minor ischemic stroke: a phase 2, randomized, controlled trial

Impaired glucose tolerance, an intermediate metabolic state between normal
glucose tolerance and diabetes mellitus defined by 2-hour post-load glucose
levels of 7.8-11.0 mmol/L, is associated with an increased risk of stroke in
patients with cardiovascular disease. Intensive glucose control with oral
antidiabetic drugs have been shown to reduce the diabetes incidence in patients
with impaired glucose tolerance without cardiovascular disease. Whether
pharmacotherapeutical intervention reduce the risk of cardiovascular events in
patients with TIA or minor ischemic stroke and impaired glucose tolerance is
unknown.

To examine the safety, tolerability, and effect on glucose metabolism of
metformin treatment in non-diabetic patients with TIA or minor ischemic stroke
and impaired glucose tolerance.

This is a phase 2, randomized, controlled, open-label trial with blind outcome
assessment among 40 non-diabetic patients with impaired glucose tolerance who
recently had a TIA or minor ischemic stroke.

Patients will be randomized for metformin (up to a maximum of 2,000mg/day) or
no oral antidiabetic drug on top of optimal standard treatment including
lifestyle advice.

Patients will be followed for 3 months, in which they will be examined by a
neurologist twice and will undergo a vena puncture twice (2 times including
oral glucose tolerance test). Furthermore, half of the patients will be on
metformin treatment during 3 months (2 tablets metformin a day). Up to 20% of
the patients can experience mainly mild, gastrointestinal side effects at the
beginning of metformin treatment, which can be minimized by slow introduction
of the drug.