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ABSTRACT Background Repurposing glucagon‐like peptide‐1 (GLP‐1) and GIP/GLP‐1 receptor agonists (RAs) for idiopathic intracranial hypertension (IIH) represents an attractive alternative to current treatments, supported by evidence of potent metabolic effects and reductions in cerebrospinal fluid secretion and intracranial pressure in vivo. Methods We evaluated the safety and efficacy of GLP‐1 RAs and GIP/GLP‐1 RAs in IIH. MEDLINE and Scopus databases were searched for randomized‐controlled trials (RCT), non‐randomized clinical trials, or registries in adults with IIH. Results Two clinical trials (one RCT and one non‐randomized case–control) and two registries, comprising 1550 IIH patients (768 receiving GLP‐1 or GIP/GLP‐1 RAs) were included. Compared with standard‐of‐care, GLP‐1 or GIP/GLP‐1 RAs were associated with a significantly lower risk of papilledema (RR: 0.25; 95% CI: 0.15–0.43; p < 0.01) and visual disturbances or blindness (RR: 0.41; 95% CI: 0.18–0.92; p = 0.03), and a near‐significant trend toward reduced headache risk (RR: 0.61; 95% CI: 0.34–1.07; p = 0.08). Additionally, GLP‐1 RAs significantly reduced monthly headache days at 3 months (MD = −3.64; 95% CI: −6.26 to −1.03; p < 0.01) and at the end of follow‐up (MD = −4.82; 95% CI: −8.80 to −0.85; p = 0.02). No association was detected between GLP‐1 RAs and body mass index. No serious adverse events or treatment discontinuations were reported; mild gastrointestinal adverse events and nausea occurred in 88% (95% CI: 0.46–1.00) of GLP‐1 RA‐treated patients. Conclusions GLP‐1 and dual GIP/GLP‐1 RAs are associated with a significantly lower risk of papilledema and visual disturbances or blindness and a lower headache risk compared with standard‐of‐care. Additionally, GLP‐1 RAs significantly reduce the monthly headache burden. Well‐designed RCTs are needed to robustly evaluate the effects of GLP‐1 and GIP/GLP‐1 RAs in IIH, which likely extend beyond their weight‐loss‐inducing properties. Trial Registration PROSPERO registration ID: CRD42025650082 GLP‐1 and dual GIP/GLP‐1 RAs are associated with a significantly lower risk of papilledema and visual disturbances or blindness and a lower headache risk compared with standard‐of‐care. Additionally, GLP‐1 RAs significantly reduce the monthly headache burden.

Highlights Despite the common practice of switching patients from one medicine to another—to improve efficacy, safety, or tolerability—guidance on how to do so is uncommon. During this time of global shortage of glucagon‐like peptide‐1 receptor agonist (GLP‐1 RA) ± glucose‐dependent insulinotropic polypeptide (GIP) RA therapies, this research letter offers a quick clinical reference of rough equivalency between GLP‐1 ± GIP RA for A1c and body weight reduction in people with type 2 diabetes.