Effects of the GLP-1 receptor agonist liraglutide on bupivacaine-induced sciatic nerve block in a rat model

Adding high-dose perineural liraglutide to bupivacaine prolonged sciatic nerve block in rats, with median sensory block increasing from 120 to 170 minutes, motor block from 115 to 160 minutes, and proprioceptive block from 115 to 170 minutes. It also reduced perineural inflammation without visible myelin damage at 24 hours. Systemic liraglutide did not reproduce the prolongation.

Journal article — randomized controlled animal study. Population: male Wistar rats undergoing sciatic nerve block. Sample size: 40 male Wistar rats. Follow-up: 24 hours. Interventions: Perineural bupivacaine 0.3 ml 0.5% plus perineural liraglutide 0.2 ml, 1.8 mg/kg; Perineural bupivacaine 0.3 ml 0.5% plus perineural liraglutide 0.2 ml, 3.6 mg/kg; Perineural liraglutide alone 0.5 ml, 3.6 mg/kg; Perineural bupivacaine 0.3 ml 0.5% plus systemic liraglutide 3.6 mg/kg intraperitoneal.

High-dose perineural liraglutide with bupivacaine prolonged sensory block (170 [160-180] vs 120 [107.5-130] min, p = 0.009), motor block (160 [160-170] vs 115 [100-120] min, p = 0.007), and proprioceptive block (170 [167.5-170] vs 115 [100-122.5] min, p = 0.009) compared with bupivacaine alone. Systemic liraglutide did not reproduce this effect. Perineural inflammation was reduced in liraglutide-treated groups (p < 0.001), with no evidence of myelin damage at 24 h.

This paper expands the known neuroprotective and anti-inflammatory profile of liraglutide to a peripheral nerve block setting, suggesting it could act locally as an adjuvant to bupivacaine. It does not establish human dosing, long-term nerve safety, or whether the effect extends to other local anaesthetics or block types.

Key findings

• High-dose perineural liraglutide (3.6 mg/kg) prolonged sensory block from 120 [107.5-130] to 170 [160-180] min versus bupivacaine alone (p = 0.009).
• High-dose perineural liraglutide prolonged motor block from 115 [100-120] to 160 [160-170] min versus bupivacaine alone (p = 0.007).
• High-dose perineural liraglutide prolonged proprioceptive block from 115 [100-122.5] to 170 [167.5-170] min versus bupivacaine alone (p = 0.009).
• Systemic liraglutide (3.6 mg/kg intraperitoneal) did not reproduce the block-prolonging effect.
• Perineural inflammation was reduced in liraglutide-treated groups compared with bupivacaine alone (p < 0.001).
• No evidence of myelin damage was observed at 24 h.

Limitations

• Proof-of-concept animal study; clinical translation to humans is not established.
• Neurotoxicity assessment was limited to myelin histopathology at 24 h, with no extended follow-up.
• Only male Wistar rats were used.
• Authors state that extended neurotoxicity and further translational studies are needed.

The record

• Journal: Journal of anesthesia
• Published: 2026-06-30
• PMID: 42377486 — DOI: 10.1007/s00540-026-03813-w
• Author countries: Turkey

Peptide profiles: Liraglutide.

All indexed evidence: Liraglutide trials & papers.

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