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Glucagon-like peptide-1 (GLP-1) receptor agonists have revolutionized weight management and are becoming essential for the treatment of obesity-related medical conditions. This study aimed to determine the pharmacokinetics, preliminary pharmacodynamics, safety, and tolerability of a long-acting GLP-1 receptor agonist, TE-8105, in overweight or obese adults without T2DM. An open-label study of four single ascending dose cohorts (A1-A4, 0.5, 0.75, 1.5, and 3.0 mg TE-8105, respectively) and two multiple dose cohorts (B1 flat dosing, 1.0 mg TE-8105 Q2W SC for 5 doses, and B2 titration dosing, sequence 2 × 1.5, 2 × 2.0, 2 × 2.5, and 3 × 3.0 mg Q2W SC) was conducted using a combination of in-patient and out-patient assessments. The half-life of TE-8105 was about 120 h. There was no accumulation after flat dosing, but mean (SD) accumulation ratios were 3.75 (0.86) for C_max and 3.00 (0.65) for AUC following titration dosing. The mean % decrease in body weight from baseline to the end of study visit for titration dosing was 2.06%, with 4/8 participants maintaining weight loss of ≥5%. Treatment-related treatment emergent adverse effects (TEAEs) were consistent with the mechanism of action of TE-8105 and dose-dependent, including nausea (Part A: 16.7%; Part B: 21.4%), abdominal pain (Part A: 4.2%), constipation (Part A: 4.2%; Part B: 7.1%), and vomiting (Part A: 4.2%; Part B: 7.1%). Overall, TE-8105 was safe and well tolerated with pharmacokinetics potentially allowing for less frequent SC dosing than currently available GLP-1 receptor agonists.