Liraglutide

Mechanism (as reported)

A class review reported that GLP-1 receptor agonists share mechanisms including augmentation of glucose-stimulated insulin secretion, suppression of glucagon secretion (at hyper- or euglycemia), deceleration of gastric emptying, and reduction in calorie intake and body weight. (PMID: 33068776) A connectomics study reported that liraglutide activated GLP-1 receptor–expressing inhibitory neurons (TRHArc neurons) that inhibited hunger-promoting AgRP neurons in a mouse satiety circuit, affecting feeding and weight-related effects. (PMID: 39627618)

Key findings (each cites a source)

• A systematic review of randomized controlled trials in adults without diabetes (26 RCTs; 15,491 participants) reported that liraglutide produced weight loss of up to 5.8% (95% CI 3.6% to 8.0%) after 26 weeks compared with placebo. [PMID 39761578]
• In the same systematic review, gastrointestinal adverse events were reported as the most common adverse events for GLP-1 receptor agonists, and serious adverse events and adverse events requiring discontinuation were rare. [PMID 39761578]
• A review of GLP-1 receptor agonists in type 2 diabetes described shared mechanisms including augmentation of hyperglycemia-induced insulin secretion, suppression of glucagon secretion at hyper- or euglycemia, deceleration of gastric emptying, and reduction in calorie intake and body weight. [PMID 33068776]
• A mouse connectomics study reported that liraglutide activated TRH+ Arc neurons predicted to express the Glp1r gene and that activating these neurons inhibited AgRP neurons and feeding; silencing TRHArc neurons reportedly caused overeating/weight gain and attenuated liraglutide's effect on body weight. [PMID 39627618]
• A pharmacovigilance analysis of individual case safety reports in EudraVigilance (01/01/2021–30/05/2023) identified psychiatric adverse event reports for liraglutide and found depression as the most commonly reported psychiatric adverse event; the analysis also reported deaths and life-threatening outcomes in association with some reports (including liraglutide). [PMID 38265519]
• A randomized-trial-focused review on obesity and GLP-1 agonists summarized multiple studies on GLP-1 agonists for weight loss and reported that GLP-1 agonists have been shown to promote weight loss in preclinical and clinical studies. [PMID 37445623]
• A preclinical mouse study reported that liraglutide reduced Ang II-induced aortic dissection incidence and mortality in APOE(-/-) mice and described an effect on M1 macrophage polarization mediated via GLP-1R activation, with pathway elements including PI3K/AKT and CXCL3 noted in the study. [PMID 38548245]