Mazdutide (IBI362 / LY3305677)

Structure: Synthetic oxyntomodulin analog. Dual agonist at GLP-1 and glucagon receptors with a fatty-acid acylation for albumin binding and once-weekly half-life. Originated as LY3305677 at Eli Lilly, licensed to Innovent Biologics for development in China as IBI362.

Status:

• Approved in China for chronic weight management (2025) under the trade name Xinerda (mazdutide injection).
• Type 2 diabetes indication is in late-stage Chinese trials.
• Not approved in the United States, EU, UK, or Australia at the time of writing.

Dosage (Phase 2 / approved Chinese label range):

• Titration: 1.5mg/week for 4 weeks, then 3mg/week for 4 weeks, then 4.5mg/week (and 6mg/week explored in Phase 2)
• Higher-dose Phase 2 (obesity): 9mg/week explored, with greater weight loss at the cost of more GI side effects

Administration:

• Once-weekly SubQ injection
• Pre-filled pen device used in Chinese Phase 3 trials and the approved product
• Titrate slowly to manage GI tolerability

Key Notes:

• Closest pipeline analog to survodutide (also a glucagon / GLP-1 dual agonist), with broadly similar mechanism but different molecular structure.
• Most clinical data is in Chinese populations; pharmacokinetics, dose-response, and adverse event rates in non-Asian populations are not yet well characterised.
• May be more accessible than survodutide for users in Asian markets; less accessible elsewhere via legitimate channels.
• Grey market sourcing exists internationally ahead of Western approval. Product purity is the main risk; counterfeit and underdosed product is common.
• Reduces serum uric acid in trials, which is unusual among GLP-1 class agents and potentially relevant for users with gout or hyperuricaemia.
• Same class warnings apply: pancreatitis risk (small but real), medullary thyroid carcinoma class boxed warning (extrapolated), gallbladder disease.
• Monitor: fasting glucose, HbA1c, lipid panel, ALT / AST / GGT, amylase / lipase, uric acid, heart rate.

References:

• Ji, L., Jiang, H., An, P., Deng, H., Liu, M., Li, L., Feng, L., Song, B., Han-Zhang, H., Ma, Q., & Qian, L. (2021). IBI362 (LY3305677), a weekly-dose GLP-1 and glucagon receptor dual agonist, in Chinese adults with overweight or obesity: A randomised, placebo-controlled, multiple-ascending-dose phase 1b study. eClinicalMedicine, 39, 101088. DOI: 10.1016/j.eclinm.2021.101088
• Ji, L., Gao, L., Jiang, H., Yang, J., Yu, L., Wen, J., Cai, C., Deng, H., Feng, L., Song, B., Ma, Q., & Qian, L. (2024). Safety and efficacy of a GLP-1 and glucagon receptor dual agonist mazdutide (IBI362) 9 mg and 10 mg in Chinese adults with overweight or obesity: A randomised, placebo-controlled, multiple-ascending-dose phase 1b trial. eClinicalMedicine, 73, 102691. DOI: 10.1016/j.eclinm.2024.102691
• Pocai, A. (2014). Action and therapeutic potential of oxyntomodulin. Molecular Metabolism, 3(3), 241-251. DOI: 10.1016/j.molmet.2013.12.001