ABSTRACT
Background and aims: Hyperglycaemia in acute ischaemic stroke (AIS) is common, reduces the efficacy of stroke thrombolysis and thrombectomy, with worse clinical outcomes. Insulin therapies are difficult to implement and maintain, and may cause symptomatic hypoglycaemia. An alternative treatment is Exenatide, a GLP-1 agonist that lowers blood glucose with a very low risk of hypoglycaemia. Methods: The Trial of Exenatide in Acute Ischaemic Stroke (TEXAIS) enrolled adult patients with AIS ≤9 hours of stroke onset to receive treatment with short-acting Exenatide (5μg bid subcutaneous injection) or Standard care for 5 days, or until hospital discharge (whichever sooner).Primary outcome: proportion of patients with ≥8 point improvement in NIHSS score (or NIHSS 0-1) at 7 days. Results: 350 patients randomised, median age 71 years (IQR 62, 79), and median NIHSS 4 (IQR 2, 8). Planned recruitment (n=528) stopped early due to Covid and time constraints. On Admission the median blood glucose was 6.7 (IQR 5.70, 8.50), and 42% patients had hyperglycaemia (>7.0 mmol/L). Primary outcome occurred in 97/171 (56.7%) in Standard care group vs 104/170 (61.2%) in Exenatide group [aOR: 1.22 (CI 0.79, 1.88) p=0.38]. Mean daily per-patient frequency of hyperglycaemia was significantly less in the Exenatide group (p=0.002). No episodes of hypoglycaemia reported over the treatment period. Nausea/vomiting occurred in 7/174 (4.0%) patients on Exenatide. Conclusions: In this Phase 2 trial Exenatide did not significantly reduce neurological disability at 7 days. Exenatide significantly reduced frequency of hyperglycaemic events, and was safe to use. These results warrant further investigation with larger Phase 3 trials.