A Study of LY4329090 in Participants With Obesity or Overweight Who Are Otherwise Healthy

A Phase 1, Participant- and Investigator-Blind, Single-Ascending and Multiple- Ascending Dose Study to Investigate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of LY4329090 in Participants With Obesity or Overweight

The main purpose of this study is to assess how well LY4329090 is tolerated and what side effects may occur in healthy participants with obesity or overweight. Blood tests will be performed to investigate how the body processes the study drug and how the study drug affects the body. Study participants will be in one of 2 parts. For each participant in Part A, the study will last about 10 weeks and will include a stay in the Clinical Research Unit (CRU) lasting 5 nights along with 5 outpatient visits to the CRU. For each participant in Part B, the study will last about 21 weeks and will include 4 stays totaling 11 nights along with 14 outpatient visits to the CRU.

Inclusion Criteria:

• Participant must be 18 (21 for Singapore site) to 65 years of age, inclusive, at the time of signing the informed consent.
• Are overtly healthy with no comorbidities related to body mass index (BMI).
• Have a BMI between 27.0 kilograms per square meter (kg/m²) and 40.0 kg/m², inclusive.
• Have had a self-reported stable weight for 3 months prior to screening.

Exclusion Criteria:

• Have a history or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal (GI), endocrine, hematological, or neurological disorders.

• Have a history of chronic medical conditions involving the heart, liver, or kidneys.

• Have either

  • ongoing asymptomatic bradycardia defined as less than 50 beats per minute at screening visit
  • electrocardiogram (ECG) findings at screening visit of second-degree atrioventricular block or higher, or
  • history of symptomatic bradycardia with uncorrected etiology, including diagnosis of sick sinus syndrome.

• Have an abnormal blood pressure and/or pulse rate at screening.

• Have an obesity induced by other endocrinologic disorders or diagnosed monogenetic or syndromic forms of obesity.

• Have any of the following:

  • a diagnosis of hypocalcemia or hypercalcemia, or
  • confirmed abnormal laboratory values for calcium and serum phosphorus.

• Have a known, clinically significant gastric emptying abnormality, have undergone weight loss surgery, or have had endoscopic and/or device-based therapy for obesity or have had device removal within the last 6 months.

• Have been diagnosed with type 1 or type 2 diabetes mellitus or have glycated hemoglobin A1c (HbA1c) greater than or equal to (≥) 6.5 percent (%) or 48 millimoles per mole (mmol/mol) at screening.

• Have a history or presence of psychiatric disorders, within the last 2 years, that would present a safety risk or may significantly impair the participant's ability to comply with study procedures.

• Have taken any glucose-lowering medications, including insulin, in the past 3 months before screening.

• Have received any drugs from the incretins class within 90 days prior to screening.

• Have been treated within 3 months prior to screening or plan to be treated with prescription medications that promote weight loss.

• Intend to use any weight loss medications during study participation.

• Prior (within 6 months) or planned (during the study) device-based treatment use for obesity.