Elecoglipron Phase 2 Trial Reports Weight Loss, GI AEs

Key Takeaways

• At week 26, estimated mean body-weight change across elecoglipron doses ranged from -2.6% to -10.5%, compared with -0.6% with placebo.
• The estimated proportion reaching at least 5% weight loss ranged from 40.4% to 88.8% with elecoglipron and was 15.6% with placebo.
• Adverse events occurred in 84% to 98% of elecoglipron-treated participants and 84% with placebo, most often nausea, constipation, diarrhea, headache, and vomiting. The authors said the findings support phase 3 investigation.

At week 26, estimated mean body-weight change reached -10.5% with 75 mg elecoglipron using weekly titration, compared with -0.6% with placebo in the phase 2 VISTA trial of elecoglipron. The trial enrolled adults with obesity, or with overweight and at least one weight-related condition, and no type 2 diabetes. Elecoglipron is an oral small-molecule GLP-1 receptor agonist evaluated as a once-daily tablet without food or fluid restriction.

Researchers conducted a multicenter, double-blind, randomized, controlled, phase 2 dose-ranging trial over 36 weeks at sites in Australia, Canada, Germany, Japan, Taiwan, the UK, and the USA. Adults were eligible at age 18 years or older if they had obesity with BMI at least 30 kg/m2 and no type 2 diabetes. Participants with overweight could enroll with BMI at least 27 kg/m2, at least one weight-related condition, and no type 2 diabetes. Treatment groups were assigned in a 2:3:3:3:3:5 ratio to 5 mg, 15 mg, 50 mg with every-4-weeks dose escalation, 75 mg with weekly titration, 75 mg with every-2-week titration, or matching placebo. Mean age was 48.4 years, 73% were female, and dual primary endpoints were percent change in bodyweight from baseline and proportion reaching at least 5% weight loss at week 26.

From Oct 8, 2024, to Feb 18, 2025, 472 individuals were screened, 162 did not meet inclusion criteria, and 310 were randomized. Overall, 288 participants, or 93%, completed the study, and 231, or 75%, completed assigned treatment through the protocol. At week 26, estimated mean body-weight change ranged from -2.6% with 5 mg to -10.5% with 75 mg weekly titration, compared with -0.6% with placebo. The estimated proportion reaching at least 5% weight loss ranged from 40.4% to 88.8% with elecoglipron and was 15.6% with placebo. 

Safety and tolerability were assessed in all participants who received at least one dose of study treatment. Adverse events occurred in 84% to 98% of participants across elecoglipron dose groups and in 84% with placebo. The most common events were nausea, constipation, diarrhea, headache, and vomiting.