Ecnoglutide reduces weight, improves cardiometabolic health in adults with obesity

Once-a-week treatment with ecnoglutide demonstrates superiority over placebo, with sustained reductions in body weight and improvements in cardiometabolic indexes among adults with overweight or obesity, reports a study presented at ADA 2025. 

“Ecnoglutide is a cAMP-biased long-acting GLP-1 analogue being developed for the treatment of obesity and type 2 diabetes,” said lead author Dr Linong Ji, director of Peking University Diabetes Center and the Department of Endocrinology and Metabolism, Peking University People’s Hospital, Beijing, China. 

Ji and his team conducted a double-blind, randomized, placebo-controlled phase III trial at 36 sites across China for 48 weeks. They recruited 664 adults with overweight or obesity and randomly allocated them to receive once-weekly ecnoglutide (1.2, 1.8, or 2.4 mg) or placebo. 

The mean body weight and BMI of participants at baseline were 91.3 kg and 32.5 kg/m2, respectively. Those on ecnoglutide achieved greater bodyweight reductions from baseline than those on placebo after 48 weeks (–9.9 percent to –15.4 percent vs –0.3 percent; p<0.0001). [ADA 2025, abstract 164-OR] 

Among the participants who received ecnoglutide, 77.7 percent to 92.8 percent had a weight loss ≥5 percent, 51.2 percent to 79.6 percent had ≥10-percent reductions, and up to 63.5 percent achieved ≥15-percent reductions. The use of the study drug likewise improved certain cardiometabolic indexes such as lipid profile and liver fat content. 

Safety profile 

Ecnoglutide also showed a favourable safety profile, with good tolerability despite a significantly greater proportion of participants reporting any adverse event (AE) relative to placebo users (92.8 percent to 93.4 percent vs 84.2 percent). AEs leading to treatment discontinuation occurred in 10 participants (2.0 percent), while serious AEs occurred in five ecnoglutide users (1.0 percent). 

The most common AEs reported were diarrhoea, nausea and vomiting, and decreased appetite. Most of these events were transient and mild to moderate in severity. 

“In adults with overweight or obesity, ecnoglutide once-weekly treatments led to superior and sustained bodyweight reductions over placebo and improvements in cardiometabolic indexes,” Ji said.  

Aminosterol antagonist 

Apart from GLP-1 agonists, other therapies are currently being investigated for effective weight management among patients with type 2 diabetes and obesity. 

A recent phase Ia study reported the safety and tolerability of ENT-03 in the treatment of obesity and diabetes. [ADA 2025, abstract 271-OR] 

“ENT-03 is a subcutaneously administered aminosterol antagonist of PTP1B that acts in the hypothalamus to decrease weight,” according to lead author Dr Richard S. Larson, CEO and chief medical officer for Metabolics Pharma, Inc., Philadelphia, Pennsylvania, US. 

The study drug was well-tolerated in healthy participants with obesity (n=27) and those with both obesity and diabetes (n=8). No safety signals, treatment-emergent AEs, serious AEs, and AEs leading to discontinuation were reported. 

All treatment-emergent AEs were mild or moderate in severity. Of the participants, four experienced mild nausea, and two had moderate vomiting. Mild injection site reactions occurred in four individuals, but these did not need any intervention.