Metabolic / Dual GLP-1/Glucagon Agonist Research Peptides Guide

The Metabolic / Dual GLP-1/Glucagon Agonist category encompasses innovative peptides that target both GLP-1 and glucagon receptors, aiming to address obesity and related metabolic disorders. Research indicates that these compounds can synergistically enhance glucose regulation and promote weight loss through distinct but complementary mechanisms. Each peptide's clinical status varies, with some undergoing advanced trials while others have received regulatory approval in specific regions. Understanding the evidence base, mechanisms, and safety profiles of these peptides is crucial for researchers exploring their therapeutic potential.

Mazdutide (IBI362) is a dual GLP-1/glucagon receptor agonist co-developed by Innovent Biologics and Eli Lilly, with a molecular weight of 4,563.06 g/mol. This once-weekly injectable peptide is designed to harness the appetite-suppressing effects of GLP-1 alongside glucagon’s ability to enhance energy expenditure and promote hepatic fat reduction. As of June 2025, Mazdutide received approval from China's NMPA for chronic weight management, followed by an approval in September 2025 for glycemic control in type 2 diabetes, marking a significant milestone as the first dual agonist of its kind approved globally. Ongoing Phase II trials in the United States aim to further investigate its efficacy and safety in diverse populations.

Pemvidutide (ALT-801) is a dual GLP-1/glucagon receptor agonist developed by Altimmune, targeting obesity and nonalcoholic steatohepatitis (NASH/MASH). This peptide is formulated for once-weekly administration, combining the appetite suppression attributed to GLP-1 with glucagon's role in increasing energy expenditure and reducing hepatic fat. The Phase II clinical trials, including the MOMENTUM study for obesity and the IMPACT study for NASH/MASH, have been completed, demonstrating promising results that support its continued development. Anticipation for Phase III trials is growing, as researchers seek to further validate its therapeutic potential and establish robust evidence for clinical use.

Cotadutide (MEDI0382), developed by AstraZeneca (originally MedImmune), is another dual GLP-1/glucagon receptor agonist designed for once-daily administration. It aims to integrate the glucose-lowering and appetite-suppressing effects of GLP-1 with glucagon's ability to promote hepatic fat oxidation and boost energy expenditure. Phase II trials have been completed for indications including type 2 diabetes, obesity, and NASH/MASH. However, the future development of Cotadutide remains uncertain, as AstraZeneca has not progressed to Phase III trials, potentially due to mixed results and shifting priorities within its research portfolio. This underscores the complexities of peptide development in the competitive landscape of metabolic therapies.