Influence of metabolic state and body composition on the action of pharmacological treatment of migraine

Background Glucagon-like peptide-1 (GLP-1) plays a crucial role in metabolic disorders by enhancing insulin secretion, inhibiting glucagon release, and slowing gastric emptying, thereby improving glycemic control. In recent years, GLP-1 role in neuronal pathways has expanded its therapeutic potential. We aim to comprehensively evaluate the relevance of GLP-1 in headache and pain disorders. Methods A systematic literature search was conducted on PubMed and Embase (Ovid) databases using the search terms “GLP-1” and “pain”. Animal and human studies published in English language were included. Abstracts, reviews, and articles on other disorders than “pain” were excluded. Results The search strategy identified 833 hits, of which 42 studies were included in the final review. The studies were categorized into four groups: inflammatory pain and osteoarthritis, headaches, neuropathic pain and diabetic neuropathy, and visceral pain and irritable bowel syndrome. GLP-1 receptor (GLP-1R) agonists, like liraglutide, have shown analgesic effects by modulating pain hypersensitivity in animal models of inflammatory and neuropathic pain. GLP-1 is involved in migraine mechanisms and GLP-1R agonists are beneficial in individuals with idiopathic intracranial hypertension. Additionally, GLP-1R agonists reduce visceral hypersensitivity and ameliorate symptoms in patients with irritable bowel syndrome. Conclusions The therapeutic scope of GLP-1R agonists is expanding beyond traditional metabolic targets, highlighting its potential for headache and pain disorders. Engineering bimodal molecules that integrate GLP-1R agonism with specific pain-related mechanisms may offer innovative therapeutic options.

Glucagon-like peptide-1 (GLP-1) receptor agonists for headache and pain disorders: a systematic review

Halloum,

Dughem,

Beier

et al. 2024

Comparison of gepant effects at therapeutic plasma concentrations: connecting pharmacodynamics and pharmacokinetics

Boucherie,

Dammers,

Vincent

et al. 2024

Background Orally administered second-generation gepants are effective for the treatment of migraine. The intranasal administration of the third-generation gepant zavegepant might have additional benefits including a rapid onset of action, but it is not clear yet to which extent this has clinical relevance. Methods We examined the effect of zavegepant on the relaxations induced by calcitonin gene-related peptide (CGRP) in human isolated middle meningeal arteries. Furthermore, we connected the pharmacodynamics and pharmacokinetics of gepants by combining data from clinical and basic research. Results We showed that 10 nM zavegepant potently antagonized the functional response to CGRP. We also showed that all gepants are effective at inhibiting functional responses to CGRP at their therapeutic plasma concentrations. Conclusions The relatively low predicted potency of zavegepant to inhibit CGRP-induced relaxation at therapeutic systemic plasma concentrations may point to the relevance of local delivery to the trigeminovascular system through intranasal administration. This approach may have additional benefits for various groups of patients, including overweight patients.

Epidemiological linkage between migraine and diabetes mellitus: a systematic review and meta-analysis

Ha,

Nguyen,

Chu

2024

Background This study aimed to elucidate the nature and extent of the associations between diabetes mellitus (DM) and migraine through a systematic review and meta-analysis. Methods We searched the PubMed, Web of Science, and Scopus databases without a specified start date until June 2, 2024. Cross-sectional and cohort studies analyzing the risk of migraine in individuals with DM and vice versa were included. Studies without at least age and sex adjustments were excluded. Data were extracted to calculate odds ratios (ORs) and hazard ratios (HRs). Risk of bias was assessed using the Newcastle–Ottawa Quality Assessment Scale. Results Eight cross-sectional studies (131,361 patients with DM and 1,005,604 patients with migraine) and four cohort studies (103,205 patients with DM patients and 32,197 patients with migraine) were included. Meta-analyses of the cross-sectional studies showed no significant overall association between DM and migraine. Subgroup analyses revealed that type 1 diabetes reduced the odds of having migraine (OR 0.48, 95% confidence interval [CI] 0.30–0.77), while migraine without aura (MO) increased the odds of having DM (OR 1.19, 95% CI 1.02–1.39). The cohort studies indicated that DM decreased the risk of developing migraine (HR 0.83, 95% CI 0.76–0.90), and a history of migraine increased the risk of developing DM (HR 1.09, 95% CI 1.01–1.17). Conclusions DM, particularly type 1 diabetes, is negatively associated with migraine occurrence, whereas migraine, especially MO, is positively associated with DM occurrence. However, most of the results remained at a low or very low level of evidence, indicating the need for further research.