Ecnoglutide, a cAMP-biased glucagon-like peptide-1 receptor agonist (GLP-1 RA), produced 35% greater weight loss than semaglutide at 20 weeks in a head-to-head randomized trial, according to interim data presented as a late-breaking abstract at the 2026 Scientific Sessions of the American Diabetes Association (ADA) in New Orleans, Louisiana.¹
Ecnoglutide: Fast Facts
- Mechanism: cAMP-biased GLP-1 receptor agonist developed by Sciwind Biosciences; engineered to preferentially activate cAMP signaling while minimizing β-arrestin recruitment and receptor internalization
- Regulatory status: Approved by China's National Medical Products Administration for chronic weight management; Pfizer holds exclusive commercialization rights in mainland China
- Phase 3 obesity data (SLIMMER): In 664 Chinese adults with overweight or obesity, the 2.4 mg dose produced 15.4% mean weight loss at 48 weeks, with a 0.6% discontinuation rate due to gastrointestinal adverse events
- Type 2 diabetes program: Evaluated in the EECOH phase 3 trial series; phase 3 data demonstrate glycemic efficacy and weight loss versus placebo and active comparators in adults with type 2 diabetes on background therapy
Traditional GLP-1 RAs have been used to treat type 2 diabetes since 2005 and gained approval for weight management in 2014, but individual heterogeneity in glucose-lowering potency and weight reduction efficacy, along with gastrointestinal tolerability concerns, have driven interest in next-generation agents. Biased agonism selectively favoring specific intracellular signaling pathways at a receptor represents one such engineering strategy of these agents.
Ecnoglutide is designed to potently induce cAMP signaling while avoiding GLP-1 receptor internalization, a signaling profile that preclinical data suggest may translate to more pronounced glycemic and weight-loss outcomes versus semaglutide.
“Better weight loss therapies do not come from simple stacking of targets, but from precise regulation of key biological mechanisms. The head-to-head study of ecnoglutide versus semaglutide provides direct clinical evidence for this innovative concept, marking an important milestone in the translation of biased agonist mechanisms from cutting-edge science to clinical application,” Hai Pan, Founder and CEO of Sciwind Biosciences, said in a statement. “From Nobel Prize-level basic research to patient-accessible clinical products, we will remain committed to scientific translation, turning more cutting-edge scientific achievements into tangible health benefits for patients worldwide."
The SLIMMER-UP-SWITCH trial was a multicenter, randomized, open-label phase 2 study conducted at 17 centers in China, enrolling 163 adults with obesity (BMI ≥30 kg/m²).¹ Participants were randomly assigned in a 1:1 ratio to receive once-weekly subcutaneous injections of ecnoglutide or semaglutide at the same maintenance dose of 2.4 mg. The pre-specified interim analysis was conducted at week 20 of a 60-week treatment period.
At week 20, the least-squares mean percentage change in body weight from baseline was −12.8% in the ecnoglutide group versus −9.5% in the semaglutide group (P <.0001).¹ The proportion of participants achieving ≥5% weight loss was 99% with ecnoglutide versus 86% with semaglutide (P <.01), and ≥10% weight loss was achieved by 74% versus 40%, respectively (P <.001). Ecnoglutide also produced a 20% greater reduction in waist circumference (10.5 cm vs 8.7 cm; P <.05), with superior reductions in arm and neck circumference as well.¹
The drug's safety profile in SLIMMER-UP-SWITCH was consistent with prior SLIMMER program data. Its favorable gastrointestinal tolerability is particularly notable because gastrointestinal adverse events are among the primary reasons patients discontinue GLP-1 RA therapy. In the earlier phase 3 SLIMMER obesity trial in 664 adults, the treatment discontinuation rate due to gastrointestinal adverse events was 0.6%.¹
The data arrive as the field weighs increasingly differentiated next-generation incretin strategies. In the phase 3 EECOH-1 trial in type 2 diabetes, ecnoglutide demonstrated pronounced improvements versus placebo in glycemic control and body weight, with a favorable safety and tolerability profile, supporting its potential as a treatment option for type 2 diabetes.
Ecnoglutide is currently approved by China's National Medical Products Administration for chronic weight management, with Pfizer holding exclusive commercialization rights in mainland China. No US regulatory submission has been announced for the obesity indication. The 60-week SLIMMER-UP-SWITCH trial remains ongoing.
"These new findings add to the clinical evidence that new generation biased GLP-1 therapies in weight management and metabolic treatment can offer patients enhanced efficacy, tolerability and safety,” said Jean-Christophe Pointeau, Global Senior Vice President and President of Pfizer China.
References
Ji L, et al. Efficacy and safety of a biased GLP-1 receptor agonist ecnoglutide in adults with overweight or obesity. Lancet Diabetes Endocrinol. 2025;13(9):777–789.
Guo W, et al. Discovery of ecnoglutide — a novel, long-acting, cAMP-biased glucagon-like peptide-1 (GLP-1) analog. JHEP Reports. 2023. https://doi.org/10.1016/j.biopha.2023.115148
El Eid L, et al. Biased agonism and polymorphic variation at the GLP-1 receptor: implications for the development of personalised therapeutics. Pharmacol Res. 2022;184:106411.
