Evolutionary perspectives on GLP-1 receptor agonists and the modern obesity, sedentary behaviour, and loneliness epidemics

CONTEXT: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have transformed obesity and diabetes treatments and show promise for many other health conditions, warranting an examination of their broader health effects. OBJECTIVE: We examine obesity, sedentary behaviour, and loneliness through an evolutionary medicine framework, assessing GLP-1RAs' role in buffering or exacerbating mismatches between novel environments and our evolved physiology. METHODS: We searched for relevant GLP-1RA papers through PubMed utilising keywords such as "physical activity," "social," and "qualitative," and synthesise important findings in this narrative review. RESULTS: GLP-1RAs buffer against the negative health effects of obesogenic foods through the drugs' effects on our neurobiology. These drugs may mitigate the effects of sedentary lifestyles, as it is easier to exercise without excess weight. However, rapid drug-induced weight loss may reduce fat-free mass if behavioural interventions (e.g. strength training) are not undertaken. Finally, we discuss the mismatch of reduced social eating and associated loneliness. While little data exists on the social effects of GLP-1RAs, emerging evidence suggests that GLP-1RAs may alleviate or intensify loneliness depending on an individual's milieu and specific drug response. CONCLUSION: Our novel environments increasingly challenge human health. GLP-1RAs may help us manage these mismatches in some ways and exacerbate them in others.