Ecnoglutide shows favorable safety, BMI reduction in adolescents with obesity in phase 1b trial

A once-weekly, cyclic adenosine monophosphate (cAMP)–biased glucagon-like peptide-1 (GLP-1) receptor agonist was well tolerated and produced double-digit reductions in body mass index (BMI) among adolescents with obesity over 20 weeks, according to phase 1b data presented as a late-breaking abstract at the 62nd Annual Meeting of the European Association for the Study of Diabetes (EASD).¹ No drug-related serious adverse events were reported with ecnoglutide, and its pharmacokinetic profile in adolescents was broadly consistent with that observed in adults.¹

The sponsor, Sciwind Biosciences, described the study as the first completed trial of a biased GLP-1 receptor agonist in adolescents, and a phase 3 adolescent trial is now underway.¹ "In the treatment of adolescent obesity, safety always comes first," said Junfen Fu, professor and principal investigator at the Children's Hospital, Zhejiang University School of Medicine, who added that the larger trial will evaluate effects on growth, development, and metabolic markers.¹

Ecnoglutide phase 1b trial design in adolescents aged 12 to 17 years

The multicenter, randomized, double-blind, placebo-controlled trial (NCT07143227) enrolled 48 adolescents aged 12 to 17 years with obesity at Tanner stages 2 to 5.¹ All participants had achieved less than a 5% BMI reduction after at least 12 weeks of diet and exercise intervention alone.¹ Participants were randomized 1:1:1:1 to ecnoglutide 1.2 mg, 1.8 mg, or 2.4 mg or placebo for 20 weeks.¹ Safety and tolerability were the primary objectives; pharmacokinetic and pharmacodynamic parameters were secondary.¹

Safety, BMI reduction, and metabolic outcomes with ecnoglutide in adolescents

Gastrointestinal events, including nausea, diarrhea, and vomiting, were the most frequently reported adverse events and were mostly mild and transient.¹ Drug exposure increased in a dose-dependent manner, which investigators said supports use of the adult dosing regimen in adolescents.¹

At week 20, BMI decreased by 11.2% to 12.6% across ecnoglutide groups vs 0.0% with placebo, and body weight decreased by 10.4% to 12.1% vs a 1.2% gain with placebo (P < .0001 for all comparisons).¹ Weight reduction was evident by week 4.¹ Waist and neck circumference, hemoglobin A1c, triglycerides, and blood pressure also improved vs placebo, although specific values were not reported in the release.¹

Pediatric obesity burden and GLP-1 receptor agonist treatment options

Citing the World Obesity Atlas 2026, the sponsor reported that China had approximately 62 million children and adolescents aged 5 to 19 years with high BMI in 2025, including approximately 33 million with obesity.¹ No antiobesity medication is currently approved for adolescents in China.¹

In the United States, the American Academy of Pediatrics recommends that clinicians offer pharmacotherapy to adolescents aged 12 years and older with obesity as an adjunct to health behavior and lifestyle treatment.³ Semaglutide 2.4 mg is approved for this population based on the STEP TEENS trial, in which mean BMI changed by −16.1% vs 0.6% with placebo at 68 weeks.⁴

Ecnoglutide biased agonism mechanism and adult phase 3 SLIMMER data

Ecnoglutide preferentially activates cAMP signaling at the GLP-1 receptor, an approach the sponsor says limits activation of pathways associated with gastrointestinal adverse events and receptor desensitization.¹ That tolerability rationale has not been tested head-to-head against conventional GLP-1 receptor agonists. The drug is approved in China for adult weight management and adult type 2 diabetes.¹ In the adult phase 3 SLIMMER trial, mean percent change in body weight at 40 weeks was –9.1%, –10.9%, and –13.2% with ecnoglutide 1.2 mg, 1.8 mg, and 2.4 mg, respectively, compared with 0.1% with placebo.²

Limitations of the ecnoglutide adolescent data and next steps

These findings come from a small, short, single-country study with roughly 12 participants per arm, reported as a conference abstract rather than a peer-reviewed publication. The 20-week duration cannot capture effects on linear growth, pubertal progression, or weight maintenance after discontinuation, and generalizability beyond Chinese adolescents is unknown. The phase 3 trial will enroll more participants over a longer treatment period and systematically assess growth, development, glycemia, lipids, and liver function.¹

References

1. Hangzhou Sciwind Biosciences Co, Ltd. EASD 2026 | Ecnoglutide demonstrates favorable safety profile in adolescents with obesity. News release. PR Newswire. September 30, 2026. Accessed September 30, 2026. https://www.prnewswire.com/news-releases/easd-2026--ecnoglutide-demonstrates-favorable-safety-profile-in-adolescents-with-obesity-302894192.html

2. Ji L, Gao L, Xue H, et al. Efficacy and safety of a biased GLP-1 receptor agonist ecnoglutide in adults with overweight or obesity: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Diabetes Endocrinol. 2025;13(9):777-789. doi:10.1016/S2213-8587(25)00141-X

3. Hampl SE, Hassink SG, Skinner AC, et al. Clinical practice guideline for the evaluation and treatment of children and adolescents with obesity. Pediatrics. 2023;151(2):e2022060640. doi:10.1542/peds.2022-060640

4. Weghuber D, Barrett T, Barrientos-Pérez M, et al. Once-weekly semaglutide in adolescents with obesity. N Engl J Med. 2022;387(24):2245-2257. doi:10.1056/NEJMoa2208601