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GALLOP-2

Glucagon-like peptide-1 receptor agonist in large vessel occlusion treated by endovascular therapy (GALLOP-2): a multicentre, prospective, randomised, open-label, blinded endpoint trial

Year of Publication: 2026

Authors: Wang H, Wang A, Ko H, ..., for the GALLOP 2 Investigators.

Citation: Wang H, et al. GALLOP-2: Glucagon-like peptide-1 receptor agonist in large vessel occlusion treated by endovascular therapy. SSRN Preprint, May 2026.

Link: https://ssrn.com/abstract=6724402

Clinical Question

Does peri-procedural subcutaneous semaglutide improve 90-day functional outcomes when added to endovascular thrombectomy in patients with acute LVO stroke who have not received intravenous thrombolysis?

Bottom Line

In patients with acute anterior circulation LVO stroke undergoing EVT without IVT, semaglutide 0.5 mg SC given before and 7 days after thrombectomy improved 90-day functional outcomes (common OR 1.46, 95% CI 1.03–2.09; p=0.035) without increasing mortality or serious adverse events, though symptomatic intracranial haemorrhage was numerically more frequent.

        Major Points
        First phase 3 RCT of a GLP-1 receptor agonist as a neuroprotective adjunct to endovascular thrombectomy.
Primary outcome (mRS shift at 90 days) favored semaglutide: common OR 1.46 (95% CI 1.03–2.09; p=0.035).
Benefit driven by higher proportion of patients achieving excellent functional outcome (mRS 0–1).
No significant differences in 90-day mortality (18.1% vs 14.9%) or serious adverse events (17.6% vs 15.9%).
Symptomatic intracranial haemorrhage was numerically higher with semaglutide (10.9% vs 5.7%) — warrants further safety evaluation.
Findings support further trials to confirm efficacy and define the role of GLP-1RAs across broader stroke populations.

      

Design

Study Type: Investigator-initiated, phase 3, multicentre, prospective, randomised, open-label, blinded endpoint (PROBE) trial

Randomization: 1

Blinding: Open-label treatment with blinded outcome assessment; 90-day mRS centrally adjudicated by an independent blinded expert panel; radiological outcomes determined by central core imaging laboratory blinded to allocation.

Allocation: 1:1, block randomisation with fixed block size of 4, stratified by study site, via centralised interactive web response system.

Enrollment Period: January 25, 2025 to October 7, 2025

Follow-up Duration: 90 days

Centers: 19

Countries: China

Sample Size: 388

Analyzed: 388

Analysis: No patients lost to follow-up; primary analysis on ordinal mRS shift using common odds ratio.

Power Calculation: Based on Tang's Wilcoxon-Mann-Whitney U power method using subgroup data from GALLOP without IVT; 370 participants provided 90% power to detect the treatment effect at two-sided alpha 0.05; target inflated to 390 to allow for 5% attrition.

Registration: ClinicalTrials.gov NCT06788626

Inclusion Criteria

Age ≥18 years
Acute LVO involving terminal internal carotid artery, M1, or dominant M2 segment of middle cerebral artery
Disabling stroke with NIHSS ≥6
Perfusion defect >50% of middle cerebral artery territory
Presentation within 24 hours of last-known-well
If onset <6 hours: ASPECTS ≥6
If onset 6–24 hours: salvageable ischaemic penumbra on CT/MR perfusion (mismatch ratio ≥1.8 and/or mismatch volume ≥15 mL)
Written informed consent from patient or legally authorised representative

Exclusion Criteria

Prior use of intravenous thrombolysis (alteplase, tenecteplase, or urokinase)
Pre-stroke modified Rankin Scale ≥3 (age <80) or ≥2 (age ≥80)
Tandem occlusion of extracranial internal carotid artery and intracranial vessels
Simultaneous occlusions of bilateral anterior circulation or both anterior and posterior circulation
Contraindications to GLP-1 receptor agonists

Baseline Characteristics

Overall:

Median Age (years): 70.5 (IQR 60–77)
Male n (%): 235 (60.6%)
Female n (%): 153 (39.4%)
Median Baseline NIHSS: 16 (IQR 12–19)

Arms

Field	Semaglutide + EVT	Control
N	193	195
Intervention	Semaglutide 0.5 mg subcutaneous immediately after randomisation (before recanalisation) and a second 0.5 mg subcutaneous dose 7 days after endovascular thrombectomy, in addition to EVT.	Endovascular thrombectomy alone with standard care per Chinese National Guidelines.
Duration	Two doses (peri-procedural and day 7); follow-up 90 days	Single procedure; follow-up 90 days

Outcomes

Outcome	Type	Control	Intervention	HR / OR / RR	P-value
Ordinal shift in distribution of modified Rankin Scale (mRS) scores	Primary	Standard therapy + EVT (n=195)	Semaglutide + EVT (n=193) — improved mRS distribution	1.46	0.035
Excellent functional outcome (mRS 0–1) at 90 days	Secondary	Higher proportion achieved mRS 0–1 with semaglutide (drove the primary outcome benefit); specific percentages not reported in available text
Functional independence (mRS 0–2) at 90 days	Secondary	Reported as secondary outcome; specific values not available in extracted text
Ambulatory and self-care capability (mRS 0–3) at 90 days	Secondary	Reported as secondary outcome; specific values not available in extracted text
Change in NIHSS score from baseline to discharge	Secondary	Specific values not available in extracted text
Health-related quality of life (EQ5D-5L and Barthel Index) at 90 days	Secondary	Specific values not available in extracted text
Final infarct volume on brain MR or CT within 72 hours after EVT	Secondary	Specific values not available in extracted text
All-cause death at 90 days	Safety	29 (14.9%)	35 (18.1%)
Symptomatic intracranial haemorrhage within 48 hours (Heidelberg ≥2 with NIHSS worsening ≥4 or NIHSS subcategory ≥2)	Safety	11 (5.7%)	21 (10.9%)
Serious adverse events within 90 days	Safety	31 (15.9%)	34 (17.6%)
Death (90 days)	Adverse	Semaglutide 35/193 (18.1%) vs Standard 29/195 (14.9%)
Symptomatic intracranial haemorrhage (48h)	Adverse	Semaglutide 21/193 (10.9%) vs Standard 11/195 (5.7%)
Serious adverse events (90 days)	Adverse	Semaglutide 34/193 (17.6%) vs Standard 31/195 (15.9%)

Subgroup Analysis

Not detailed in available text.

Criticisms

Open-label design (PROBE), though outcome assessment was blinded.
Conducted entirely in China — generalisability to other populations unclear.
Numerical increase in symptomatic intracranial haemorrhage (10.9% vs 5.7%) requires confirmation in larger trials.
Borderline statistical significance (p=0.035) with lower 95% CI bound near 1.03.
Excluded patients who received IVT — applicability limited to EVT-only population.
Preprint, not yet peer reviewed.

Funding

Noncommunicable Chronic Diseases - National Science and Technology Major Project (2024ZD0527900); Gerald Choa Neuroscience Research Program Fund (H.K., B.Y.I.).

Based on: GALLOP-2 (2026)

Authors: Wang H, Wang A, Ko H, ..., for the GALLOP 2 Investigators.

Citation: Wang H, et al. GALLOP-2: Glucagon-like peptide-1 receptor agonist in large vessel occlusion treated by endovascular therapy. SSRN Preprint, May 2026.

Content summarized and formatted by NeuroTrials.ai.

GALLOP-2

(2026)

Objective

Phase 3 PROBE RCT testing whether semaglutide (GLP-1 receptor agonist) before and after EVT improves 90-day functional outcome in anterior LVO stroke without prior IVT.

Study Summary

• Primary 90-day mRS shift: cOR 1.46 (1.03-2.09).
• sICH 10.9% vs 5.7% (NS).
• SAE 17.6% vs 10.3% (NS); malignant edema 14.5% vs 10.3% (NS).
• ICAD 64%; eTICI 2c-3 84%.

Intervention

Two doses of semaglutide 0.5 mg SC (before EVT and 1 week after) vs standard medical treatment

Inclusion Criteria

China, multicenter. NIHSS >=6; terminal ICA/M1/dominant-M2 occlusion; planned EVT within 24 h without IVT; 0-6 h ASPECTS >=6 or 6-24 h perfusion mismatch.

Study Design

Arms: Semaglutide + EVT vs standard medical treatment + EVT

Patients per Arm: Semaglutide n=193 vs Control n=195 (total 388)

Outcome

• Primary 90-day mRS shift: cOR 1.46 (1.03-2.09).
• sICH: 10.9% vs 5.7% (NS).
• SAE: 17.6% vs 10.3% (NS).
• Malignant edema: 14.5% vs 10.3% (NS).

Bottom Line

Major Points

First phase 3 RCT of a GLP-1 receptor agonist as a neuroprotective adjunct to endovascular thrombectomy.
Primary outcome (mRS shift at 90 days) favored semaglutide: common OR 1.46 (95% CI 1.03–2.09; p=0.035).
Benefit driven by higher proportion of patients achieving excellent functional outcome (mRS 0–1).
No significant differences in 90-day mortality (18.1% vs 14.9%) or serious adverse events (17.6% vs 15.9%).
Symptomatic intracranial haemorrhage was numerically higher with semaglutide (10.9% vs 5.7%) — warrants further safety evaluation.
Findings support further trials to confirm efficacy and define the role of GLP-1RAs across broader stroke populations.

Study Design

Study Type: Investigator-initiated, phase 3, multicentre, prospective, randomised, open-label, blinded endpoint (PROBE) trial
Randomization: Yes
Blinding: Open-label treatment with blinded outcome assessment; 90-day mRS centrally adjudicated by an independent blinded expert panel; radiological outcomes determined by central core imaging laboratory blinded to allocation.
Sample Size: 388
Follow-up: 90 days
Centers: 19
Countries: China

Primary Outcome

Definition: Ordinal shift in distribution of modified Rankin Scale (mRS) scores

Control	Intervention	HR/OR	P-value
Standard therapy + EVT (n=195)	Semaglutide + EVT (n=193) — improved mRS distribution	1.46 (1.03–2.09)	0.035

Limitations & Criticisms

Open-label design (PROBE), though outcome assessment was blinded.
Conducted entirely in China — generalisability to other populations unclear.
Numerical increase in symptomatic intracranial haemorrhage (10.9% vs 5.7%) requires confirmation in larger trials.
Borderline statistical significance (p=0.035) with lower 95% CI bound near 1.03.
Excluded patients who received IVT — applicability limited to EVT-only population.
Preprint, not yet peer reviewed.

Citation

Wang H, et al. GALLOP-2: Glucagon-like peptide-1 receptor agonist in large vessel occlusion treated by endovascular therapy. SSRN Preprint, May 2026.

View Original Publication →

GALLOP-2

Glucagon-like peptide-1 receptor agonist in large vessel occlusion treated by endovascular therapy (GALLOP-2): a multicentre, prospective, randomised, open-label, blinded endpoint trial

Clinical Question

Bottom Line

Major Points

Design

Inclusion Criteria

Exclusion Criteria

Baseline Characteristics

Arms

Outcomes

Subgroup Analysis

Criticisms

Funding

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