Visual and Neurological Outcomes Following Glucagon-Like Peptide-1 Receptor Agonist Therapy and Bariatric Surgery in Idiopathic Intracranial Hypertension: A Network Meta-Analysis
Restricted accessResearch articleFirst published online 2026
Visual and Neurological Outcomes Following Glucagon-Like Peptide-1 Receptor Agonist Therapy and Bariatric Surgery in Idiopathic Intracranial Hypertension: A Network Meta-Analysis
Idiopathic intracranial hypertension (IIH) is commonly linked to obesity. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and bariatric surgery may improve outcomes beyond conventional therapy, but comparative evidence is limited.
Methods:
We systematically searched MEDLINE, EMBASE, and Cochrane from inception until June 2025. Eligible randomized and observational studies compared GLP-1RAs or bariatric surgery (each plus conventional care) against conventional management. Primary outcomes were the change in papilledema, visual acuity, and visual field. Secondary outcomes included body mass index (BMI), retinal nerve fiber layer (RNFL) thickness, monthly headache days, and risks of papilledema, visual disturbance, and headache. Pairwise random-effects meta-analyses and frequentist network meta-analysis (P-scores) were performed.
Results:
Out of 429 records, 8 studies were included. Versus conventional therapy, GLP-1RAs reduced BMI (mean difference −1.55 kg/m2; 95% confidence interval [CI]: −2.13 to −0.97) and lowered risks of papilledema (relative risk [RR]: 0.47; 95% CI: 0.34–0.65), visual disturbance (RR: 0.48; 95% CI: 0.24–0.98), and headache (RR: 0.78; 95% CI: 0.69–0.88). Changes in papilledema severity and RNFL thickness were not different; visual acuity favored GLP-1RAs at the end of follow-up, whereas visual field values were worse at some time points. In indirect comparisons with bariatric surgery, no significant differences were detected across outcomes.
Conclusions:
Adjunctive GLP-1RA therapy may be associated with weight loss and improved clinical/ophthalmic outcomes in IIH relative to conventional care, with a signal for worse visual fields at certain time points. Indirect comparisons suggest comparable efficacy to bariatric surgery. High-quality randomized trials are needed to define comparative effectiveness, safety, and optimal use.
FriedmanDI, LiuGT, DigreKB. Revised diagnostic criteria for the pseudotumor cerebri syndrome in adults and children. Neurology2013;81(13):1159–1165; doi: 10.1212/WNL.0b013e3182a55f17
2.
ChenJ, WallM. Epidemiology and risk factors for idiopathic intracranial hypertension. Int Ophthalmol Clin2014;54(1):1–11; doi: 10.1097/IIO.0b013e3182aabf11
3.
MollanSP, AguiarM, EvisonF, et al.The expanding burden of idiopathic intracranial hypertension. Eye (Lond)2019;33(3):478–485; doi: 10.1038/s41433-018-0238-5
4.
BestJ, SilvestriG, BurtonB, et al.The incidence of blindness due to idiopathic intracranial hypertension in the UK. Open Ophthalmol J2013;7:26–29; doi: 10.2174/1874364101307010026
5.
MollanSP, GrechO, SinclairAJ. Headache attributed to idiopathic intracranial hypertension and persistent post-idiopathic intracranial hypertension headache: A narrative review. Headache2021;61(6):808–816; doi: 10.1111/head.14125
CurryWTJr, ButlerWE, BarkerFG.2nd., Rapidly rising incidence of cerebrospinal fluid shunting procedures for idiopathic intracranial hypertension in the United States, 1988–2002. Neurosurgery2005;57(1):97–108; discussion 97-108; doi: 10.1227/01.neu.0000163094.23923.e5
8.
Ghaffari-RafiA, MehdizadehR, KoAWK, et al.Idiopathic intracranial hypertension in the United States: Demographic and socioeconomic disparities. Front Neurol2020;11:869; doi: 10.3389/fneur.2020.00869
9.
ShaiaJK, SharmaN, KumarM, et al.Changes in prevalence of idiopathic intracranial hypertension in the United States between 2015 and 2022, stratified by sex, race, and ethnicity. Neurology2024;102(3):e208036; doi: 10.1212/WNL.0000000000208036
10.
Collaborators GBDAB. Global, regional, and national prevalence of adult overweight and obesity, 1990–2021, with forecasts to 2050: A forecasting study for the Global Burden of Disease Study 2021. Lancet2025;405(10481):813–838; doi: 10.1016/S0140-6736(25)00355-1
11.
MollanSP, TahraniAA, SinclairAJ. The potentially modifiable risk factor in idiopathic intracranial hypertension: Body weight. Neurol Clin Pract2021;11(4):e504–e507; doi: 10.1212/CPJ.0000000000001063
12.
ColmanBD, BoonstraF, NguyenMN, et al.Understanding the pathophysiology of idiopathic intracranial hypertension (IIH): A review of recent developments. J Neurol Neurosurg Psychiatry2024;95(4):375–383; doi: 10.1136/jnnp-2023-332222
13.
AbbottS, ChanF, TahraniAA, et al.Weight management interventions for adults with idiopathic intracranial hypertension: A systematic review and practice recommendations. Neurology2023;101(21):e2138–e2150; doi: 10.1212/WNL.0000000000207866
14.
MitchellJL, LyonsHS, WalkerJK, et al.The effect of GLP-1RA exenatide on idiopathic intracranial hypertension: A randomized clinical trial. Brain2023;146(5):1821–1830; doi: 10.1093/brain/awad003
15.
JirapinyoP, JinDX, QaziT, et al.A meta-analysis of GLP-1 after Roux-En-Y gastric bypass: Impact of surgical technique and measurement strategy. Obes Surg2018;28(3):615–626; doi: 10.1007/s11695-017-2913-1
16.
YiangouA, MollanSP, SinclairAJ. Idiopathic intracranial hypertension: A step change in understanding the disease mechanisms. Nat Rev Neurol2023;19(12):769–785; doi: 10.1038/s41582-023-00893-0
17.
HigginsJP, LiT, DeeksJJ. Choosing effect measures and computing estimates of effect. In: Cochrane Handbook for Systematic Reviews of Interventions. Word Press; 2019; pp. 143–176.
18.
AzzamAY, EssibayiMA, FarkasN, et al.Efficacy of Tirzepatide Dual GIP/GLP-1 receptor agonist in patients with idiopathic intracranial hypertension. a real-world propensity score-matched study. Endocrinol Diabetes Metab2025;8(2):e70019; doi: 10.1002/edm2.70019
19.
AzzamAY, EssibayiMA, VaishnavD, et al.Liraglutide for idiopathic intracranial hypertension: A real-world propensity score-matched study. Ann Clin Transl Neurol2025;12(4):746–755; doi: 10.1002/acn3.52300
20.
AzzamAY, EssibayiMA, VaishnavD, et al.Semaglutide as an adjunctive therapy to standard management for idiopathic intracranial hypertension: A real-world data-based retrospective analysis. medRxiv2024:2024.11.12.24317197; doi: 10.1101/2024.11.12.24317197
21.
KrajncN, ItariuB, MacherS, et al.Treatment with GLP-1 receptor agonists is associated with significant weight loss and favorable headache outcomes in idiopathic intracranial hypertension. J Headache Pain2023;24(1):89; doi: 10.1186/s10194-023-01631-z
22.
KravetzL, LeemanS, RegevT, et al.The effect of glucagon-like peptide-1 agonists on ocular parameters in idiopathic intracranial hypertension patients: A retrospective study. Eye (Lond)2025;39(10):2090–2095; doi: 10.1038/s41433-025-03807-0
23.
MirdadRT, MorsyMM, AzzamAY, et al.Comparison of bariatric surgery and community weight management for idiopathic intracranial hypertension in a multicenter retrospective cohort study. Sci Rep2025;15(1):13982; doi: 10.1038/s41598-025-97081-5
24.
MollanSP, MitchellJL, YiangouA, et al.Association of amount of weight lost after bariatric surgery with intracranial pressure in women with idiopathic intracranial hypertension. Neurology2022;99(11):e1090–e1099; doi: 10.1212/WNL.0000000000200839
25.
O’LearyS, PriceA, Camarillo-RodriguezL, et al.Impact of GLP-1 receptor agonists on idiopathic intracranial hypertension clinical and neurosurgical outcomes: A propensity-matched multi-institutional cohort study. J Neurosurg2025;143(4):1037–1047; doi: 10.3171/2025.1.JNS242357
26.
DruckerDJ. GLP-1 physiology informs the pharmacotherapy of obesity. Mol Metab2022;57:101351; doi: 10.1016/j.molmet.2021.101351
27.
BoerGA, HayDL, TupsA. Obesity pharmacotherapy: Incretin action in the central nervous system. Trends Pharmacol Sci2023;44(1):50–63; doi: 10.1016/j.tips.2022.11.001
28.
ChenB, YuX, Horvath-DianoC, et al.GLP-1 programs the neurovascular landscape. Cell Metab2024;36(10):2173–2189; doi: 10.1016/j.cmet.2024.09.003
29.
LvC, HanS, ShaZ, et al.Cerebral glucagon-like peptide-1 receptor activation alleviates traumatic brain injury by glymphatic system regulation in mice. CNS Neurosci Ther2023;29(12):3876–3888; doi: 10.1111/cns.14308
MarkeyKA, MollanSP, JensenRH, et al.Understanding idiopathic intracranial hypertension: Mechanisms, management, and future directions. Lancet Neurol2016;15(1):78–91; doi: 10.1016/s1474-4422(15)00298-7
32.
WallM, KupersmithMJ, KieburtzKD, NORDIC Idiopathic Intracranial Hypertension Study Group. et al.The idiopathic intracranial hypertension treatment trial: Clinical profile at baseline. JAMA Neurol2014;71(6):693–701; doi: 10.1001/jamaneurol.2014.133
33.
WallM, McDermottMP, KieburtzKD, et al.Effect of acetazolamide on visual function in patients with idiopathic intracranial hypertension and mild visual loss: The idiopathic intracranial hypertension treatment trial. JAMA2014;311(16):1641–1651; doi: 10.1001/jama.2014.3312
34.
HathawayJT, ShahMP, HathawayDB, et al.Risk of nonarteritic anterior ischemic optic neuropathy in patients prescribed semaglutide. JAMA Ophthalmol2024;142(8):732–739; doi: 10.1001/jamaophthalmol.2024.2296
35.
KatzBJ, LeeMS, LincoffNS, et al.Ophthalmic complications associated with the antidiabetic drugs semaglutide and tirzepatide. JAMA Ophthalmol2025;143(3):215–220; doi: 10.1001/jamaophthalmol.2024.6058
36.
ZhangDL, FinnAP. Glucagon-like peptide-1 receptor agonists and the eye. Curr Opin Ophthalmol2025;36(5):407–413; doi: 10.1097/icu.0000000000001137
37.
SimoR, HernandezC. GLP-1R as a target for the treatment of diabetic retinopathy: Friend or foe? Diabetes2017;66(6):1453–1460; doi: 10.2337/db16-1364
38.
VilsbollT, BainSC, LeiterLA, et al.Semaglutide, reduction in glycated haemoglobin and the risk of diabetic retinopathy. Diabetes Obesity Metabolism2018;20(4):889–897; doi: 10.1111/dom.13172
39.
MarchandL, LuytonC, BernardA. Glucagon-like peptide-1 (GLP-1) receptor agonists in type 2 diabetes and long-term complications: FOCUS on retinopathy. Diabet Med2021;38(1):e14390; doi: 10.1111/dme.14390
40.
YriHM, RönnbäckC, WegenerM, et al.The course of headache in idiopathic intracranial hypertension: A 12-month prospective follow-up study. Eur J Neurol2014;21(12):1458–1464; doi: 10.1111/ene.12512
41.
FriedmanDI, QuirosPA, SubramanianPS, and the NORDIC IIHTT Study Group. et al.Headache in idiopathic intracranial hypertension: Findings from the idiopathic intracranial hypertension treatment trial. Headache2017;57(8):1195–1205; doi: 10.1111/head.13153
42.
WestgateCSJ, IsraelsenIME, JensenRH, et al.Understanding the link between obesity and headache-with focus on migraine and idiopathic intracranial hypertension. J Headache Pain2021;22(1):123; doi: 10.1186/s10194-021-01337-0
43.
HalloumW, DughemYA, BeierD, et al.Glucagon-like peptide-1 (GLP-1) receptor agonists for headache and pain disorders: A systematic review. J Headache Pain2024;25(1):112; doi: 10.1186/s10194-024-01821-3
44.
DickerD, SagyYW, RamotN, et al.Bariatric metabolic surgery vs glucagon-like peptide-1 receptor agonists and mortality. JAMA Netw Open2024;7(6):e2415392; doi: 10.1001/jamanetworkopen.2024.15392
45.
SmitsMM, HolstJJ. Endogenous glucagon-like peptide (GLP)-1 as alternative for GLP-1 receptor agonists: Could this work and how? Diabetes Metab Res Rev2023;39(8):e3699; doi: 10.1002/dmrr.3699
46.
ZhengZ, ZongY, MaY, et al.Glucagon-like peptide-1 receptor: Mechanisms and advances in therapy. Signal Transduct Target Ther2024;9(1):234; doi: 10.1038/s41392-024-01931-z
47.
KoskinasKC, Van CraenenbroeckEM, AntoniadesC, ESC Scientific Document Group. et al.Obesity and cardiovascular disease: An ESC clinical consensus statement. Eur Heart J2024;45(38):4063–4098; doi: 10.1093/eurheartj/ehae508
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