Probably in direction, and not by the amounts the papers print. Idiopathic intracranial hypertension raises pressure inside the skull, causes severe headache and swells the optic nerve, and weight loss is one of the few things established to help it, so a drug producing large weight loss ought to work. A meta-analysis of nine studies covering 13,257 participants reports that it does, with papilledema at a risk ratio of 0.38 and headache at 0.73 [1]. It also reports something that cannot be true, and that number is the reason to distrust the size of the rest. The eye is somewhere these drugs have produced mixed signals before, as the optic nerve evidence by indication shows.
The clinical outcomes go the expected way. Headache risk came in at a risk ratio of 0.73 (95% CI 0.61–0.86), papilledema at 0.38 (95% CI 0.25–0.56), visual worsening at 0.51 (95% CI 0.37–0.68), and needing surgical intervention at 0.76 (95% CI 0.65–0.89). Mechanistically this is about as plausible as findings in this field get.
The reason to dwell on an implausible number rather than ignore it is that it calibrates the others. The mortality estimate and the papilledema estimate come from the same studies, comparing the same people. Whatever made the treated group so much less likely to die — being younger, healthier, better engaged with care, well enough to be offered an injection — was also making them less likely to lose vision. So the direction of the vision findings is probably right and the size of them is almost certainly inflated.
A second meta-analysis, built from different sources, lands in the same direction [3]. It pooled two clinical trials, one of them randomized, and two registries: 1,550 patients, 768 of them on a GLP-1 or dual GIP/GLP-1 drug. Against standard care, papilledema came in at a risk ratio of 0.25 (95% CI 0.15–0.43) and visual disturbance or blindness at 0.41 (95% CI 0.18–0.92).
Headache, at 0.61 with an interval from 0.34 to 1.07, fell short of significance. The analysis detected no association between the drugs and body mass index, and its authors suspect the effect reaches beyond weight loss. Its abstract reports no mortality figure, so the calibration argument above belongs to the first analysis, not to this one. Two pools, with papilledema at 0.38 and 0.25, agree on which way it goes.
What neither supplies is a large randomized trial. The first analysis excluded studies of patients with prior IIH treatment, which removes one source of confusion, and its abstract does not say how many of its nine studies were randomized. The second counted one among its four sources. Where a pooled study is observational, its risk ratio inherits every baseline difference that study carried.
The separate optic nerve literature is worth keeping apart from this one. Pooling eight cohorts, semaglutide carried a relative effect of 1.93 for non-arteritic anterior ischemic optic neuropathy, with a 95% confidence interval of 1.22 to 3.08 [2]. That is a different condition, a different mechanism and a different comparison, and it cuts against the idea that anything here is simply good for the optic nerve.
For someone with this diagnosis the practical position is reasonable and the numbers are not. Weight loss helps intracranial pressure, these drugs produce weight loss, and a neuro-ophthalmologist weighing one is on defensible ground. Reading 0.38 as the papilledema benefit to expect is not defensible. It is the same reason a mortality hazard ratio the authors disowned and the dialysis cohort need their baseline tables read first, and the same reason the overdose comparison gave five different answers.