A comprehensive narrative review integrating mechanistic, proteomic, epigenetic, and randomized trial data positions GLP-1 receptor agonists (semaglutide, liraglutide), dual GIP/GLP-1 agonist tirzepatide, and next-generation triple agonists (retatrutide) and glucagon-containing agents (survodutide) as candidates with effects extending beyond adiposity. Notably, newer multi-receptor agents achieve liver-fat reductions of 60–80%, with visceral and hepatic fat loss disproportionate to total weight lost — a distinction the review argues is more relevant to healthspan than scale readings. Exploratory proteomic and epigenetic analyses hint at weight-independent mechanisms, though the review explicitly cautions these fall short of proving slowed biological aging.
What distinguishes this field right now is the shift from obesity pharmacotherapy to metabolic systems biology. The cardiovascular and renal outcome trial data — SELECT, FLOW, SURMOUNT — have already moved the clinical needle, but the aging-biomarker angle remains genuinely exploratory and should be read cautiously. The aesthetic consequences — "Ozempic face," accelerated skin laxity, lean mass atrophy — represent an underappreciated clinical dimension that aesthetic and primary care practitioners increasingly must navigate. Critically, this is a narrative review by a single author at a lesser-known institution, carrying inherent selection bias risk and no pooled effect sizes. For healthy adults without obesity, extrapolating longevity benefits remains speculative. Still, the visceral-fat specificity of newer agents marks an incremental but meaningful advance over earlier weight-loss drugs, with real healthspan implications worth monitoring as longer-term trial data matures.