A Study to Evaluate AMG 133 Administered Subcutaneously in Participants With Overweight or Obesity

Prior treatment

• Uncontrolled thyroid disease, defined as thyroid-stimulating hormone (TSH) \> 6.0 mIU/L or \< 0.4 mIU/L at Screening. Participants who receive treatment for hypothyroidism are permitted if their thyroid hormone replacement dose has been stable for 3 months prior to Screening and TSH criteria are met.
• Previous surgical procedure for obesity within 6 months prior to Check-in.
• History of or current suicidal ideation (thoughts), suicide attempt(s), or major psychiatric illness (including depression) within 6 months prior to Screening.
• Use of any over-the-counter or prescription medications within 30 days or 5 half-lives (whichever is longer) before Check-in.
• Current or prior use of all herbal medicines (e.g., St. John's wort), vitamins, and supplements consumed by the participant within the 30 days prior to enrollment, unless deemed acceptable by the Investigator (or designee) and in consultation with the Sponsor.
• Participant has received a dose of an investigational drug within the past 30 days or 5 half-lives, whichever is longer, prior to Check-in.
• Have previously completed or withdrawn from this study or any other study investigating AMG 133 or have previously received the investigational product.

Other illness

• History or evidence, at Screening or Check-in, of clinically significant disorder, condition, or disease not otherwise excluded that, in the opinion of the Investigator (or designee), would pose a risk to participant safety or interfere with the study evaluation, procedures, or completion.
• History or evidence of endocrine disorder (such as Cushing's Syndrome) that can cause obesity.
• Malignancy except nonmelanoma skin cancers or cervical or breast ductal carcinoma in situ within the last 5 years.
• Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2.
• History of or current signs of gastroparesis.
• History or current signs or symptoms of cardiovascular disease (aside from controlled hypertension and controlled dyslipidemia), including but not limited to myocardial infarction, congenital heart disease, valvular heart disease, coronary revascularization, or angina.
• History or evidence of clinically significant arrhythmia at Screening, including any clinically significant findings on the ECG taken at Screening or Check-in.
• History of hypersensitivity or allergy to AMG 133 or its ingredients, unless approved by the Investigator (or designee) and in consultation with the Sponsor.
• Estimated glomerular filtration rate less than ≤ 60 mL/min/1.73 m\^2 as calculated by the Modification of Diet in Renal Disease equation at Screening or Check-in. One repeat of abnormal values will be allowed.

Lab values

• History of or active diabetes (regardless of type with the exception of gestational diabetes), or Hemoglobin A1C ≥ 6.5% (≥ 48 mmol/mol), at Screening.
• History of acute or chronic pancreatitis within 1 year prior to Check-in, or elevation in serum lipase/amylase (\> 2x the upper limit of normal) at Screening, or fasting serum triglyceride level of \> 500 mg/dL at Screening. One repeat of abnormal values will be allowed.
• Current use or prior use of any glucagon-like peptide 1 receptor (GLP-1R) agonist, GIPR glucose-dependent insulinotropic polypeptide receptor (GIPR) agonist or antagonist within the past 3 months prior to Check-in.
• Female participants of childbearing potential with a positive pregnancy test assessed at Screening or Check-in by a serum or urine pregnancy test.

Other

• Alanine aminotransferase or aspartate aminotransferase \> 2x the upper limit of normal at Screening or Check-in. One repeat of abnormal values will be allowed.
• Female participants lactating/breastfeeding or who plan to breastfeed during the study through 16 weeks after the last dose of AMG 133.
• Unwilling to adhere to contraceptive requirements through 16 weeks after the last dose of AMG 133.
• Unwilling to abide with study restrictions.
• Participants who, in the opinion of the Investigator (or designee), should not participate in this study.

• Participant has provided informed consent before initiation of any study-specific activities/procedures.
• Male or female participants, between 18 and 65 years of age (inclusive) at the time of Screening.
• Except for obesity, no clinically significant findings from medical history, physical examination, 12-lead electrocardiogram (ECG), vital signs measurements, and clinical laboratory evaluations (congenital nonhemolytic hyperbilirubinemia \[e.g., suspicion of Gilbert's syndrome based on total and direct bilirubin\] is not acceptable) as assessed by the Investigator (or designee). Participants with obstructive sleep apnea, controlled hypertension, and/or controlled dyslipidemia on stable therapies will be permitted. Participants with other mild, well-controlled comorbidities may be permitted with approval of the Investigator (or designee) in consultation with the Medical Monitor as appropriate.
• Body mass index ≥ 27 kg/m\^2 at the time of Screening.
• Have a stable body weight (\< 5 kg self-reported change) within 3 months before Screening, as assessed by the Investigator (or designee) based on participant self-report. Have not modified diet or adopted any nutritional lifestyle modification for 3 months, as assessed by the Investigator (or designee) based on participant self-report.