Head-to-Head Study Validates Clinical Advantage of cAMP-Biased GLP-1 Agonist Ecnoglutide: 35% Greater Weight Loss Than Semaglutide at Week 20
核心洞察
Interim analysis from the SLIMMER-UP-SWITCH Phase 2 trial shows ecnoglutide achieved a least-squares mean body weight reduction of -12.8% versus -9.5% for semaglutide (P<0.0001) at Week 20.
The proportion of patients achieving ≥10% weight loss was 74% with ecnoglutide compared to 40% with semaglutide (P<0.001), nearly a twofold difference.
Ecnoglutide, the world's first approved cAMP-biased GLP-1 receptor (搜索) agonist, demonstrated a 20% greater reduction in waist circumference versus semaglutide (10.5 cm vs. 8.7 cm, P<0.05).
NEW ORLEANS — Interim results from a head-to-head Phase 2 clinical trial demonstrate that ecnoglutide, the world's first approved cAMP-biased GLP-1 receptor (搜索) agonist, delivers significantly greater weight loss than semaglutide in adults with obesity (搜索), according to data presented as a Late-Breaking abstract at the 86th Scientific Sessions of the American Diabetes Association (ADA) 2026.
The SLIMMER-UP-SWITCH study, conducted across 17 research centers in China, enrolled 163 adult patients with obesity (搜索) (BMI ≥30 kg/m²) who were randomized 1:1 to receive once-weekly subcutaneous injections of either ecnoglutide or semaglutide at the same maintenance dose of 2.4 mg. The pre-specified interim analysis at Week 20 revealed that ecnoglutide produced a 35% greater reduction in body weight compared to semaglutide.
Weight Loss Outcomes
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<0.0001). The proportion of participants achieving ≥5% weight loss reached 99% with ecnoglutide compared to 86% with semaglutide (P<0.01). More strikingly, 74% of ecnoglutide-treated patients achieved ≥10% body weight loss versus only 40% in the semaglutide arm (P<0.001), representing a near doubling of the clinically meaningful response rate.
Circumference and Metabolic Improvements
Beyond weight reduction, ecnoglutide demonstrated superior effects on body circumference measures. The mean reduction in waist circumference from baseline was 10.5 cm in the ecnoglutide group and 8.7 cm in the semaglutide group (P<0.05), a 20% greater reduction. Improvements in arm circumference and neck circumference also favored ecnoglutide.
Professor Linong Ji, Director of the Department of Endocrinology at Peking University People's Hospital, emphasized the clinical significance of these findings: "Central obesity (搜索), characterized by abdominal fat accumulation, not only affects body shape but is also a key risk factor for type 2 diabetes (搜索), metabolic syndrome (搜索) and cardiovascular diseases (搜索). While effectively reducing body weight, ecnoglutide significantly improves central obesity and local fat accumulation, optimizing body shape while lowering the risk of related metabolic diseases."
Biased Agonism: Translating Nobel Prize-Winning Science
Ecnoglutide's differentiated profile stems from its mechanism as a cAMP-biased GLP-1 receptor (搜索) agonist. Traditional GLP-1 receptor agonists employ a "full pathway activation" mode, which activates weight loss signaling pathways but also frequently triggers pathways associated with gastrointestinal adverse events and receptor desensitization. Based on Nobel Prize-winning research findings, ecnoglutide optimizes GLP-1 receptor signal transduction to achieve a balance between potent efficacy and tolerability.
The safety profile observed in this head-to-head study was consistent with prior SLIMMER study results, with ecnoglutide demonstrating favorable gastrointestinal safety. In the previously reported Phase 3 SLIMMER study, which enrolled 664 Chinese adults with overweight or obesity (搜索), ecnoglutide 2.4 mg achieved an average weight loss of 15.4% at 48 weeks, with 92.8% of subjects losing more than 5% of body weight. That study also documented a mean waist circumference reduction of 12.8 cm, a 53.1% average reduction in liver fat content among subjects with baseline fatty liver disease (搜索), and significant improvements in blood pressure, blood lipids, and blood glucose. Notably, the treatment discontinuation rate due to adverse events was 2%, and discontinuation due to gastrointestinal adverse events was just 0.6%.
Clinical and Commercial Implications
Dr. Hai Pan, Founder and CEO of Sciwind Biosciences (搜索), framed the results as validation of a broader scientific philosophy: "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."
Jean-Christophe Pointeau, Global Senior Vice President and President of Pfizer China, added: "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." Pfizer holds exclusive commercialization rights for ecnoglutide in Mainland China.
Professor Ji underscored the evidentiary importance of the data: "This study provides the first direct clinical evidence validating the clinical advantages of the innovative cAMP-biased GLP-1 receptor (搜索) agonist mechanism. By optimizing GLP-1 receptor signal transduction, it delivers superior clinical benefits over traditional GLP-1 receptor agonists, providing high-quality evidence-based medical evidence for the field of weight management."
The SLIMMER-UP-SWITCH study continues with a planned 60-week treatment period, with the full dataset expected to further characterize the long-term efficacy and safety of ecnoglutide in direct comparison to semaglutide.