IBI362, LY3305677, Moshutai
Evidence Grade C — Moderate human evidence. 38 published studies, 25 human. 31 registered clinical trials.
Mazdutide is a dual GLP-1/glucagon receptor agonist developed primarily in China, where it has already been approved for weight management — making it the first drug in its class to reach any market. The glucagon component adds a mechanism that increases energy expenditure and burns liver fat, complementing the appetite suppression from GLP-1. Development for markets outside China is ongoing.
38 published studies: 25 human, 1 animal, 1 in-vitro, 21 reviews
Mazdutide has been approved in China (as Moshutai) for weight management and is in Phase III development for other markets. In the Chinese Phase III GLORY-1 trial (610 patients), the 6 mg dose achieved approximately 15% weight loss at 48 weeks with 80% liver fat reduction in participants with baseline hepatic steatosis.
Mazdutide's approval in China makes it the first dual GLP-1/glucagon agonist to receive marketing authorisation anywhere. The dramatic liver fat reduction may position it strongly for metabolic liver disease indications. Development for non-Chinese markets is ongoing.
Mazdutide combines GLP-1 receptor activation (appetite suppression) with glucagon receptor activation (increased energy expenditure and liver fat burning), similar in concept to survodutide (#160). The glucagon component directly stimulates hepatic fat oxidation, which produces significant liver fat reduction alongside weight loss.
In the Chinese Phase III GLORY-1 trial (610 patients), the highest dose achieved approximately 15% weight loss at 48 weeks, with an 80% reduction in liver fat in participants who had fatty liver at baseline. The dramatic liver fat reduction may position mazdutide strongly for metabolic liver disease, a massive unmet need. Head-to-head data showed superiority over semaglutide for both weight loss and blood sugar control in Chinese patients. Key limitations include that all Phase III evidence comes from Chinese populations only, and development outside China remains at Phase II. Eli Lilly holds the rights for markets outside China, and their Phase 2 trial results will determine whether a global filing is pursued. Remarkably low discontinuation rates (0.5-2.9%) suggest favourable tolerability. Survodutide, a competing dual GLP-1/glucagon agonist from Boehringer Ingelheim, is also in advanced development.
ASCEND-1: Lifestyle Intervention Plus Mazdutide for Weight Management
Efficacy and Safety of IBI362 in Hypertensive Patients With Overweight/Obesity
A Study of HDM1005 in Participants With T2DM Not Controlled With Metformin Alone or in Combination With a Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitor
A Study of IBI362 in Chinese Adolescents With Obesity or Overweight
Mazdutide as Adjuvant Therapy Following Sleeve Gastrectomy in Severe Obesity
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Liraglutide is marketed as Victoza for type 2 diabetes (approved 2010) and Saxenda for weight management (approved 2014). The LEADER trial, involving over 9,300 patients followed for nearly four years, established that liraglutide reduced the risk of major cardiovascular events by 13% — a landmark finding that helped establish GLP-1 treatments as a class with heart benefits. Saxenda is also approved for adolescents aged 12 and older. While historically significant, liraglutide has been substantially surpassed by newer agents. In a direct comparison, semaglutide achieved 15.8% weight loss compared to liraglutide's 6.4%. Liraglutide remains relevant as a lower-intensity option and as a benchmark against which newer treatments are measured. It has over a decade of real-world safety data, making it one of the best-understood medications in this class.
Setmelanotide is marketed as Imcivree (Rhythm Pharmaceuticals; approved November 2020 for POMC, PCSK1, or LEPR deficiency; June 2022 for Bardet-Biedl syndrome; December 2024 expanded to patients aged 2 years and older). Genetic testing confirming an eligible mutation is required before treatment. In patients with POMC or PCSK1 deficiency, approximately 80% achieved at least 10% weight loss in clinical trials. In Bardet-Biedl syndrome, 32.3% achieved the same threshold. The most common side effects are injection-site reactions and skin darkening (due to the melanocortin pathway's connection to pigmentation). Setmelanotide exemplifies precision medicine — it is highly effective in the specific genetic populations it targets but is not indicated for common obesity.
HGH Fragment 176-191 has no marketing authorisation. A Phase IIa trial in obesity (approximately 300 patients) failed to demonstrate statistically significant weight loss at any dose tested. The clinical development programme was discontinued. The disconnect between animal data (which showed significant fat reduction in obese mice) and the failed human trial is the defining feature of this compound's development history. Products available through unregulated channels lack pharmaceutical quality assurance. The failed Phase II trial represents the highest level of clinical evidence available.
