Table 3.

Human studies evaluating the analgesic effects of glucagon-like peptide 1 receptor (GLP-1R) agonists in headache and pain disorders

Study	Year	Study design	Study drug	Study duration	Disease	Study participants	Main findings
Gudbergsen et al. [21]	2021	Randomized controlled trial	Liraglutide 3 mg/daily	52 weeks	Knee osteoarthritis	156	Liraglutide did not reduce knee pain compared to placebo
Zhu et al. [22]	2023	Observational multicentre study	GLP-1R agonists	At least 5 years	Knee osteoarthritis	> 40 000	Cartilage loss velocity and incidence of knee surgery was lower in individuals treated with GLP-1R agonists
Krajnc et al. [26]	2023	Case-control study	Semaglutide and liraglutide	6 months	Idiopathic intracranial hypertension	39	Reduction in monthly headache days and acetazolamide dosage were higher in individuals treated with GLP-1R agonists
Mitchell et al. [27]	2023	Randomized controlled trial	Exenatide 10 µg twice daily	12 weeks	Idiopathic intracranial hypertension	15	Exenatide lowered intracranial pressure compared to placebo
Hellström et al. [55]	2009	Randomized controlled trial	100 and 300 µg ROSE-010	2 years and 9 months	Irritable bowel syndrome	99	Twice as many patients were responders in the primary efficacy endpoint after both ROSE-010 injections compared to placebo
Touny et al. [56]	2022	Substudy of earlier data	100 and 300 µg ROSE-010	2 years and 9 months	Irritable bowel syndrome	166	Female participants are more likely than males to respond to ROSE-010 to achieve meaningful pain relief