The aim of this study is to evaluate the efficacy of VRB-101 for body weight reduction compared to placebo in participants who have obesity or overweight with weight-related comorbidities.

This is a randomized, double-blind, placebo-controlled study of oral ecnoglutide (VRB-101), with 5 active arms and 1 placebo arm. The study will include a Screening Period of 4 weeks, followed by a 20-week Study Treatment Period and a 4-week Safety Follow-up Period prior to the end of study (EOS) visit.

Inclusion Criteria:

• Have hemoglobin A1c (HbA1c) <6.5%.
• Have a BMI of ≥30 kg/m2 OR ≥27 kg/m2 and <30 kg/m2 with at least 1 weight-related comorbidity.
• Have a self-reported history of stable body weight for the 3 months prior to randomization (≤5% body weight change).
• Participants of childbearing potential must be non-pregnant and non-lactating and must agree to use study-specified contraceptive methods.

Exclusion Criteria:

• Have any prior diagnosis of type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM), or other forms of diabetes mellitus. A participant with a history of gestational diabetes may be included in the study if the participant has an HbA1c < 6.5% at Screening.
• Have at least 1 laboratory value suggestive of diabetes during Screening, including 1 or more of HbA1c ≥6.5% (48 mmol/mol) or random glucose ≥200 mg/dL (11.1 mmol/L).
• Have had exposure to glucagon-like peptide -1 (GLP-1) 6 months prior to Screening or any prior history of known or suspected hypersensitivity/allergies, intolerability, or lack of efficacy to these medications. Have known or suspected hypersensitivity to study intervention(s), to selective GLP-1 receptor agonist (RA) or glucose-dependent insulinotropic peptide (GIP)/GLP-1 or GLP-1/glucagon (GCG) dual receptor agonists.
• Pregnant or breastfeeding at Screening or planning to become pregnant (self or partner) at any time within the dosing period, including follow -up, and for at least 60 days after the last dose of study intervention.