Weekly Subcutaneous <scp>VK2735</scp> , a <scp>GIP</scp> / <scp>GLP</scp> ‐1 Receptor Dual Agonist, for Weight Management: Phase 2, Randomized, 13‐Week <scp>VENTURE</scp> Study

OBJECTIVE: This study aimed to determine doses of VK2735, a novel glucagon-like peptide-1/glucose-dependent insulinotropic polypeptide (GLP-1/GIP) receptor dual agonist, that are effective for weight loss over 13 weeks of treatment. METHODS: VENTURE was a phase 2, randomized, double-blind, placebo-controlled, dose-ranging study of weekly subcutaneous VK2735 in adults with obesity or overweight and ≥ 1 weight-related comorbidity. Participants with diabetes mellitus were ineligible. The primary endpoint was percent change from baseline in body weight at Week 13. Secondary efficacy endpoints were observed and change from baseline weight loss and the proportion of participants losing ≥ 5% and ≥ 10% of baseline weight. RESULTS: Study was conducted between August 2023 and February 2024. Mean weight reduction with active treatment ranged from 9.2 kg (2.5 mg dose) to 14.6 kg (15 mg dose), corresponding to 9.1% and 14.7% weight reductions, respectively; the placebo group had a 1.8 kg (1.7%) reduction. In the active treatment groups, 93% (130/140) of participants had a ≥ 5% weight reduction, compared with 12% (4/34) of participants with placebo treatment. The common adverse events (AEs) were gastrointestinal, which decreased in reported frequency after dose titration to steady state. CONCLUSIONS: All subcutaneous doses of VK2735 significantly reduced body weight. The AE profile of VK2735 was primarily gastrointestinal, with decreased reported frequency upon continued use. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT06068946.