<p>Introduction Impaired glucose tolerance (IGT) is highly prevalent after stroke and is associated with recurrent stroke and unfavourable outcome. Objectives We aimed to assess the feasibility, safety and effects on glucose metabolism of metformin or sitagliptin in patients with transient ischaemic attack (TIA) or minor ischaemic stroke and IGT. Design We performed a multicentre, randomised, controlled, open-label phase II trial with blinded outcome assessment. Interventions Patients were randomised in a 2:1:1 ratio to 'no medication', sitagliptin or metformin. Primary and secondary outcome measures Primary outcome measures were baseline adjusted differences of 2-hour postload glucose; secondary outcome measures fasting glucose, glycosylated haemoglobin 1c (HbA1c) levels, tolerability and safety of metformin and sitagliptin at 6 months. Patients on metformin or sitagliptin were contacted by telephone for recording of possible adverse events and to support continuation of treatment at 2 weeks, 6 weeks and 3 months after inclusion. These events were not analysed as outcome measures. Results Fifty-three patients were randomised to control group, 26 to metformin and 22 to sitagliptin. We found no significant differences in 2-hour postload glucose between patients on antidiabetic drugs and controls ((-0.04 mmol/L (95% CI-0.53 to 0.45)). Patients in the treatment arms had reduced fasting glucose: ((-0.21 mmol/L (95% CI-0.36 to-0.06)) and HbA1c levels ((-1.16 mmol/mol (95% CI-1.84 to-0.49)). Thirteen patients (50%) on metformin and 7 (32%) on sitagliptin experienced side effects. Sixteen patients (61%) in the metformin and 13 (59%) in the sitagliptin group were still on treatment after 6 months. Conclusions Metformin and sitagliptin were both effective in reducing fasting glucose and HbA1c levels in patients with recent TIA or minor ischaemic stroke and IGT. However, the reduction of glucose levels and sample size was relatively small. The clinical relevance, therefore, needs to be tempered. A phase III trial is needed to investigate whether medical treatment, compared with lifestyle intervention or a combination of both, not only improves glucose metabolism in IGT, but also leads to reduction of recurrent TIA or ischaemic stroke in these patients. Trial registration number NL3048.</p>

doi.org/10.1136/bmjopen-2020-046113, hdl.handle.net/1765/136848
BMJ Open
Erasmus MC: University Medical Center Rotterdam

Elizabeth Osei, A.A.M. (Adrienne) Zandbergen, PJAM Brouwers, Laus J.M.M. Mulder, P.J. (Peter) Koudstaal, H.F. (Hester) Lingsma, … H den Hertog. (2021). Safety, feasibility and efficacy of metformin and sitagliptin in patients with a TIA or minor ischaemic stroke and impaired glucose tolerance. BMJ Open, 11(9). doi:10.1136/bmjopen-2020-046113