A once-weekly glucagon-like peptide-1 receptor agonist, ecnoglutide, significantly reduced bodyweight and improved health indicators in adult patients with overweight or obesity, according to findings from the first phase 3 trial of this novel drug.
In a randomized, double-blind, placebo-controlled phase 3 trial in China, researchers evaluated ecnoglutide in 664 adult patients aged 18 to 75 years who had overweight or obesity but not diabetes. The participants received weekly subcutaneous injections of ecnoglutide (1.2 mg, 1.8 mg, or 2.4 mg) or placebo for 48 weeks, along with diet and exercise counseling.
At week 48, those receiving 2.4 mg of ecnoglutide had a mean weight reduction of 15.4% compared with –0.3% among those receiving placebo. This corresponded to a mean absolute weight loss of 13.8 kg. The 1.8-mg and 1.2-mg ecnoglutide groups lost 13.3% and 9.9% of bodyweight, respectively.
In the 2.4 mg group, 93% of the participants achieved at least 5% weight loss—a threshold considered clinically meaningful for cardiometabolic benefits—vs 14% in the placebo group. Additionally, 80% reached ≥ 10% weight loss, 64% reached ≥ 15%, and 28% lost ≥ 20%. None of the participants in the placebo group reached the 20% threshold.
The study also showed improvements in secondary outcomes, including reductions in waist circumference, body mass index, systolic blood pressure, fasting glucose, insulin levels, and lipid parameters such as triglycerides and low-density lipoprotein cholesterol. The participants also reported better quality-of-life scores. Among those with elevated liver fat, ecnoglutide significantly reduced liver fat content.
Adverse events were common but mostly mild gastrointestinal symptoms such as nausea, vomiting, and diarrhea. These events declined over time. Treatment discontinuation because of adverse events occurred in 2% of the participants receiving ecnoglutide. No cases of pancreatitis or medullary thyroid carcinoma were reported. One participant in the 2.4-mg ecnoglutide group was diagnosed with papillary thyroid cancer, assessed as unrelated to treatment.
The trial, conducted at 36 sites in China and funded by Hangzhou Sciwind Biosciences, evaluated ecnoglutide—a cAMP-biased glucagon-like peptide-1 receptor agonist designed to selectively activate weight-related signaling pathways. This selective activation may potentially reduce receptor desensitization compared to unbiased GLP-1 agonists, though head-to-head comparisons are needed. Weight reduction began by week 4 and continued through week 48 without plateauing.
While the study was conducted only in China, limiting generalizability to other populations until confirmed in broader trials, the findings supported the potential of ecnoglutide as a treatment option for long-term weight management in patients with overweight or obesity.
Disclosures can be found in the study.
