Poststroke hyperglycemia is associated with worse outcome, but trials using intravenous insulin have shown inconsistent results . Exenatide, a synthetic glucagon-like peptide-1 receptor (GLP-1R) agonist, reduces blood glucose without causing hypoglycemia . Moreover, in vitro and animal studies indicate that it may have a neuroprotective action .
Eleven patients (eight males, three females, median age 80 years, 49–84 years, two with history of diabetes, eight received tissue plasminogen activator) were recruited prospectively in a nonrandomized pilot study between 2010 and 2011. Exenatide, five-micrograms, was administered subcutaneously within 12 h of ischemic stroke onset and then twice daily for the duration of their hospital stay. Adverse events and finger-prick glucose levels were assessed during the hospital stay, followed by a three-month modified Rankin Scale.
Exenatide was started at a median time of nine-hours (4.17–11.5 h) after stroke onset and was continued for a median duration of six-days (one-eight days). There were no serious adverse events or deaths related to exenatide. Mild nausea (n = 6) and vomiting (n = 5) were common adverse events but were always successfully controlled within the first 24 h of starting antiemetics and did not lead to any other complications. There was no symptomatic hypoglycemia and the rate of hyperglycemia (defined as ≥8.6 mmol/l) was low (4.9%) (Fig. 1).
This is the first study of a GLP-1R agonist in human acute stroke patients. Exenatide, when administered with prompt antiemetic therapy, was safe and tolerable in acute ischemic stroke patients and did not worsen any patient's neurological or functional outcome. We recommend prophylactic antiemetic therapy when exenatide is given in the setting of acute stroke. Further trials are indicated to confirm the effectiveness of exenatide in controlling poststroke hyperglycemia.