A once-daily oral small-molecule GLP-1 receptor agonist produced progressive, dose-dependent weight loss without food or fluid restrictions, according to a study published on Jun. 11. The results support larger phase 3 trials for long-term weight management.
Researchers evaluated the efficacy, safety, and tolerability of oral non-peptide small-molecule elecoglipron in adults with obesity or overweight and at least one weight-related health condition but without diabetes. The multicenter, randomized, double-blind, placebo-controlled phase 2 clinical trial was conducted across Australia, Canada, Germany, Japan, Taiwan, the United Kingdom, and the United States.
Adults with a body mass index (BMI) of at least 30 kg/m² or those overweight with a BMI of at least 27 kg/m² plus one additional condition were eligible. Individuals with diabetes or recent use of diabetes or weight-loss medications were excluded. A total of 310 adult participants were randomly assigned to receive either active oral elecoglipron or placebo in varying regimens over a treatment period of 36 weeks.
The primary outcomes measured included percentage change in body weight from baseline and the proportion who lost at least five percent of their body weight after 26 weeks. At week 26, estimated average weight loss ranged from 2.6% to 10.5% for low- and high-dose groups respectively; those on placebo lost an average of only 0.6%. By week 36, participants taking higher doses achieved up to an average of 11.8% reduction in body weight compared to just 0.3% among those receiving placebo.
The use of elecoglipron was also associated with reductions in BMI, waist circumference, systolic blood pressure, and markers such as high-sensitivity C-reactive protein; these improvements generally increased with dose but should be interpreted as changes in risk markers rather than evidence for reduced clinical events.
Gastrointestinal adverse events such as nausea and diarrhea were most common but typically mild to moderate and resolved over time; no deaths occurred during the trial period nor any clinically diagnosed pancreatitis cases reported. AstraZeneca funded the study and contributed to its design and reporting.
