Obesity pharmacotherapy reimagined: The era of multi-receptor agonists and next-generation metabolic modulators, perspectives and controversies.

Narrative review of emerging obesity pharmacotherapies

“This review examines the evolving landscape of obesity pharmacotherapy beyond injectable GLP-1RAs.”

Multi-receptor agonists such as retatrutide achieve weight reductions of 20–24%

“Multi-receptor agonists represent the most transformative developments: triple agonists such as retatrutide achieve weight reductions of 20–24%, while dual GLP-1/glucagon agonists like survodutide and mazdutide show strong efficacy with particular promise for metabolic-associated steatotic liver disease.”

Oral GLP-1 agonists like orforglipron offer comparable efficacy to injectables and improve accessibility

“Oral GLP-1 agonists, including orforglipron, offer comparable efficacy to injectables while potentially improving global accessibility by eliminating cold-chain requirements and simplifying manufacturing.”

Agents like bimagrumab address lean mass preservation during weight loss

“Body composition optimization through agents like bimagrumab addresses lean mass preservation during potent anorectic therapy.”

Existing reviews have limited synthesis of emerging agents and guidance on personalization

“Existing reviews have focused predominantly on approved GLP-1RAs, with limited synthesis of emerging multi-receptor agonists, oral formulations, and body composition–targeted agents, while guidance on treatment personalization and sequencing strategies remains limited.”