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. 2023 Jul 18;24(1):89.
doi: 10.1186/s10194-023-01631-z.

Treatment with GLP-1 receptor agonists is associated with significant weight loss and favorable headache outcomes in idiopathic intracranial hypertension

Nik Krajnc  1   2 , Bianca Itariu  3 , Stefan Macher  1   2 , Wolfgang Marik  2   4 , Jürgen Harreiter  3 , Martin Michl  5 , Klaus Novak  2   6 , Christian Wöber  1   2 , Berthold Pemp #  5 , Gabriel Bsteh #  7   8
Affiliations

Treatment with GLP-1 receptor agonists is associated with significant weight loss and favorable headache outcomes in idiopathic intracranial hypertension

Nik Krajnc et al. J Headache Pain. .

Abstract

Background: In idiopathic intracranial hypertension (IIH), sustained weight loss is the main pillar in modifying disease course, whereby glucagon-like peptide-1 receptor agonists (GLP-1-RAs) could present an attractive treatment option.

Methods: In this open-label, single-center, case-control pilot study, patients with IIH (pwIIH) and a body mass index (BMI) of ≥ 30 kg/m2 were offered to receive a GLP-1-RA (semaglutide, liraglutide) in addition to the usual care weight management (UCWM). Patients electing for UCWM only served as a control group matched for age-, sex- and BMI (1:2 ratio). The primary endpoint was the percentage weight loss at six months (M6) compared to baseline. Secondary endpoints included the rate of patients with a weight loss of ≥ 10%, monthly headache days (MHD), the rate of patients with a ≥ 30% and ≥ 50% reduction in MHD, visual outcome parameters, and adverse events (AEs).

Results: We included 39 pwIIH (mean age 33.6 years [SD 8.0], 92.3% female, median BMI 36.3 kg/m2 [IQR 31.4-38.3]), with 13 patients being treated with GLP-1-RAs. At M6, mean weight loss was significantly higher in the GLP-1-RA group (-12.0% [3.3] vs. -2.8% [4.7]; p < 0.001). Accordingly, weight loss of ≥ 10% was more common in this group (69.2% vs. 4.0%; p < 0.001). Median reduction in MHD was significantly higher in the GLP-1-RA group (-4 [-10.5, 0.5] vs. 0 [-3, 1]; p = 0.02), and the 50% responder rate was 76.9% vs. 40.0% (p = 0.04). Visual outcome parameters did not change significantly from baseline to M6. Median reduction in acetazolamide dosage was significantly higher in the GLP-1-RA group (-16.5% [-50, 0] vs. 0% [-25, 50]; p = 0.04). AEs were mild or moderate and attributed to gastrointestinal symptoms in 9/13 patients. None of the AEs led to premature treatment discontinuation.

Conclusions: This open-label, single-center pilot study suggests that GLP-1-RAs are an effective and safe treatment option for achieving significant weight loss with a favorable effect on headache, leading to reduced acetazolamide dosage in pwIIH.

Keywords: Glucagon-like peptide-1; Headache; Idiopathic intracranial hypertension; Visual worsening; Weight loss.

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Conflict of interest statement

Nik Krajnc: has participated in meetings sponsored by, received speaker honoraria or travel funding from BMS/Celgene, Janssen-Cilag, Merck, Novartis, Roche and Sanofi-Genzyme and held a grant for a Multiple Sclerosis Clinical Training Fellowship Programme from the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

Bianca Itariu: declares no conflict of interest relevant to this study.

Stefan Macher: declares no conflict of interest relevant to this study.

Wolfgang Marik: declares no conflict of interest relevant to this study.

Jürgen Harreiter: has participated in meetings sponsored by, received speaker/consultancy honoraria or travel funding from Novo Nordisk, Sanofi, Novartis, Eli Lilly, Boehringer-Ingelheim. He has received unrestricted research grants from Bayer and Astra Zeneca.

Martin Michl: declares no conflict of interest relevant to this study.

Klaus Novak: declares no conflict of interest relevant to this study.

Christian Wöber: has received honoraria consultancy/speaking from Apomedica, Curelator, Eli Lilly, Grünenthal, Hermes, Lundbeck, Novartis, Pfizer, Ratiopharm/Teva, and Stada.

Berthold Pemp: declares no conflict of interest relevant to this study.

Gabriel Bsteh: has participated in meetings sponsored by, received speaker honoraria or travel funding from Biogen, Celgene/BMS, Lilly, Merck, Novartis, Roche, Sanofi-Genzyme and Teva, and received honoraria for consulting Biogen, Celgene/BMS, Novartis, Roche, Sanofi-Genzyme and Teva. He has received unrestricted research grants from Celgene/BMS and Novartis.

Figures

Fig. 1
Fig. 1
GLP-1 is secreted from enteroendocrine cells where it activates intestinal vagal afferents, located in the gut and portal circulation, further activating GLP-1-producing neurons in the nucleus tractus solitarii. These neurons project to several food-regulating areas, including the ventral tegmental area, the nucleus accumbens and the hypothalamus. There, GLP-1 directly activates POMC/CART neurons and indirectly inhibits, via GABAergic transmission, the NPY/AgRP neurons, which collectively results in signals reducing food intake. Efferent pathways, which originate in the brain stem, subsequently signal to peripheral organs to close the loop of feeding behavior and glucose metabolism regulation. GLP-1 receptors are also expressed on the choroid plexus epithelial cells, where the binding of GLP-1 reduces Na + K + ATPase activity, leading to decreased CSF secretion and consequently decreased ICP. Created with BioRender.com. AgRP: agouti-related peptide, AP: area postrema, CART: cocaine- and amphetamine-regulated transcript, CSF: cerebrospinal fluid, ENS: enteric nervous system, GLP-1: glucagon-like peptide-1, Hyp: hypothalamus, ICP: intracranial pressure, NPY: neuropeptide Y, NTS: nucleus tractus solitarii, POMC: proopiomelanocortin, SFO: subfornical organ
Fig. 2
Fig. 2
Flow chart of inclusion/exclusion process. BMI: body mass index, FUP: follow-up, GLP-1-RA: glucagon-like peptide-1 receptor agonist, UCWM: usual care weight management, VIIH: Vienna Idiopathic Intracranial Hypertension database
Fig. 3
Fig. 3
Weight loss in patients treated with GLP-1-RAs and controls. **p < 0.01, ***p < 0.001
Fig. 4
Fig. 4
Change in monthly headache days (MHC) in patients treated with GLP-1-RAs and controls (a). Fifty percent responder rate at M6 was 75.0% and 33.3% in the GLP-1-RA and the UCWM group, respectively (b). *p < 0.05, **p < 0.01
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