Ecnoglutide Shows Promise as Next-Generation Obesity Treatment

A novel drug, ecnoglutide, has demonstrated significant efficacy in weight loss in obese or overweight individuals without diabetes, according to the results of a Phase III clinical trial recently published in The Lancet Diabetes & Endocrinology. Administered once weekly, this GLP-1 receptor agonist with a novel functional bias led to weight reductions of up to 13% after 40 weeks of treatment, with a favorable safety profile.

The findings reinforce the therapeutic potential of this molecule as an emerging alternative within the growing group of GLP-1-based medications, which have transformed the approach to obesity in recent years.

Clinically significant weight reductions

The trial enrolled 664 adults with overweight or obesity (body mass index [BMI] ≥28 kg/m², or ≥24 kg/m² with associated comorbidities) and no diabetes diagnosis. They were randomly assigned to receive one of three weekly doses of ecnoglutide (1.2 mg, 1.8 mg, or 2.4 mg) or placebo for 40 weeks.

The results showed an average reduction in body weight of 9.1% at the lowest dose , 10.9% at the intermediate dose , and 13.2% at the highest dose , compared with a 0.1% change in the placebo group. In absolute terms, this equates to a weight loss of up to 13.8 kilograms, compared with 200 grams in the control group.

Furthermore, 87% of participants receiving the highest dose of ecnoglutide achieved at least a 5% reduction in body weight , a clinically relevant threshold. This proportion was 84% ​​at the intermediate dose and 77% at the lowest dose, compared to only 16% in the placebo group.

Mechanism of action of ecnoglutide

Ecnoglutide belongs to a family of drugs that act as glucagon-like peptide-1 (GLP-1) receptor agonists, which stimulate insulin secretion, delay gastric emptying, and decrease appetite. What distinguishes this molecule from other well-known treatments, such as semaglutide or liraglutide , is its “functional bias” : it has been designed to preferentially favor the intracellular cyclic adenosine monophosphate (cAMP) pathway .

This bias toward cAMP may confer greater efficacy and less activation of other pathways that could be associated with adverse effects, although more comparative studies are needed to confirm these benefits, the study states.

Regarding safety, treatment-related adverse events were common but mostly mild to moderate and gastrointestinal in nature , such as nausea, vomiting, or diarrhea, following a similar profile to other GLP-1 inhibitors. Treatment-related adverse events were observed in 155 (93%) of 166 participants in the ecnoglutide 1.2 mg group, 154 (93%) of 166 participants in the ecnoglutide 1.8 mg group, 156 (93%) of 167 participants in the ecnoglutide 2.4 mg group, and 139 (84%) of 165 participants in the placebo group. Only 10 participants discontinued treatment due to these side effects, suggesting good overall tolerability.

The authors emphasize that no unexpected safety signals were detected during the 40-week study and highlight that most adverse events were transient and manageable.

New therapeutic options

With the growing number of people with obesity worldwide—more than 1 billion, according to the World Health Organization (WHO)—the need for effective, safe, and sustainable drug therapies is increasingly urgent. GLP-1 agonists have revolutionized this field, and ecnoglutide could represent a new generation of these drugs.

“In obese or overweight adults without diabetes, weekly administration of ecnoglutide resulted in superior and sustained body weight reduction compared with placebo, with a favorable safety profile,” the researchers concluded in the publication.

Although still under investigation, these results support its potential as a treatment for weight management , either as monotherapy or as part of a comprehensive approach along with diet, exercise, and lifestyle changes.

Following this Phase III trial, ecnoglutide’s efficacy will need to be confirmed in more diverse populations , including those with type 2 diabetes or other metabolic comorbidities. Its long-term impact on cardiovascular health markers, quality of life, and risk of more serious adverse events will also be assessed.

In addition, clinical development could include direct comparisons with other drugs in its class, such as semaglutide or tirzepatide, to determine whether differences in molecular mechanisms translate into relevant clinical benefits.

With a once-weekly formulation and a robust efficacy profile, ecnoglutide is emerging as a potential new pharmacological tool in the treatment of obesity, a complex chronic disease that requires a multidisciplinary and sustained approach.

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First published in GACETA MEDICA. A third-party contributor translated and adapted the article from the original. In case of discrepancy, the original will prevail.

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