Glibenclamide / Glyburide

Falcão L, et al. Clinical Neurology and Neurosurgery, 2025, 252, 108847.

A meta-analysis was conducted to evaluate the therapeutic application of Glibenclamide, a SUR1 inhibitor, in patients with aneurysmal subarachnoid hemorrhage (aSAH). Four randomized controlled trials (n = 290) were included. The studies assessed clinical outcomes such as the modified Rankin Scale (mRS) at 90 and 180 days, mortality, hydrocephalus, rebleeding, and hospital stay. Statistical analysis employed fixed- or random-effects models based on heterogeneity (I²), calculating risk ratios and mean differences. Glibenclamide demonstrated no significant improvement in mRS scores (90 days: MD = 0.06; 180 days: MD = -0.43) or other outcomes. However, meta-regression revealed a significant correlation between Glibenclamide dosage and mRS (p = 0.0007), suggesting dose-dependence. These findings indicate Glibenclamide's experimental use remains inconclusive, warranting further standardized trials to determine its clinical efficacy in neuroprotection following aSAH.

Sheth KN, et al. The Lancet Neurology, 2024, 23(12), 1205-1213.

In the CHARM phase 3 randomized, double-blind, placebo-controlled trial, intravenous glibenclamide (8.6 mg over 72 h) was evaluated for its potential to improve functional outcomes in patients aged 18-70 years with large hemispheric infarction. Patients (n=431) were selected based on ASPECTS 1-5 or ischaemic core volume (80-300 mL), and treatment was initiated within 10 hours of stroke onset. The primary endpoint was the 90-day modified Rankin Scale score. While glibenclamide administration did not yield a statistically significant improvement in functional outcomes (common OR 1.17; p=0.42), the study demonstrated acceptable safety, with hypoglycaemia occurring in 6% of treated patients. The early termination of the trial limited conclusive interpretation, but intravenous glibenclamide remains a promising candidate for targeted subpopulation studies in acute ischaemic stroke management.

ElKhooly IA, et al. Life Sciences, 2024, 357, 123046.

In a diabetic nephropathy model, glibenclamide (0.6 mg/kg) was administered alone or in combination with vitamin B1 (70 mg/kg) or calcitriol (0.1 μg/kg) in rats induced with type 2 diabetes via high fructose, salt, and fat intake followed by STZ injection (40 mg/kg, i.p.). Co-treatment significantly preserved renal function and reduced histopathological damage. Mechanistically, combination therapy downregulated HMGB1, TLR4, NF-κB, and TNF-α, while enhancing antioxidant responses via Nrf2 and glutathione upregulation. Additionally, α-SMA and collagen deposition were markedly reduced. These results suggest that glibenclamide's efficacy against diabetic nephropathy is potentiated by vitamin B1 or calcitriol through modulation of inflammation, oxidative stress, and fibrosis pathways.

Castor RGME, et al. European Journal of Pharmacology, 2024, 984, 177035.

In a murine model of cardiac damage induced by a high refined carbohydrate (HC) diet, glibenclamide was evaluated for its cardioprotective effects through inhibition of the NLRP3 inflammasome. After 8 weeks on the HC diet, mice received glibenclamide (20 mg/kg/day, gavage) for 4 weeks. Cardiac morphology was assessed post-mortem, and cardiac function evaluated both in vivo via invasive catheterization and ex vivo using Langendorff perfusion. Western blot and in situ fluorescence staining were used to measure NLRP3 expression, reactive oxygen species (ROS), and caspase-1 activation. Glibenclamide treatment reversed HC diet-induced hypertrophy and fibrosis, reduced ROS generation, and suppressed IL-1β and caspase-1 activity without improving insulin resistance. These findings demonstrate glibenclamide's application as an NLRP3-targeting agent for mitigating diet-induced cardiac inflammation and structural remodeling.

Zhuang Z, et al. International Journal of Pharmaceutics, 2025, 675, 125526.

In this study, glibenclamide was encapsulated in MMP-responsive PEG-PCL-ACPP micelles (Gliben@P-P-A) via an emulsion method. Specifically, 2 mg of glibenclamide and 20 mg of PEG-PCL-ACPP were dissolved in DMSO and ultrasonically dispersed into PBS, followed by filtration and dialysis (MWCO 14 kDa) to eliminate DMSO. The final product was purified using centrifugal filtration (100 kDa cutoff) and sterile filtration. In vitro and in vivo studies confirmed the biocompatibility and spinal cord lesion-targeting capability of Gliben@P-P-A. Therapeutically, it significantly mitigated progressive hemorrhagic necrosis, suppressed inflammation, and exerted neuroprotective effects. The control micelle (P-P-A) without glibenclamide was prepared using an identical protocol. This work demonstrates the potential of Gliben@P-P-A as a targeted nanodrug delivery platform for acute spinal cord injury treatment.