This study is designed to test how well the combination of MET233 with MET097 works to treat individuals with obesity or overweight with or without diabetes.

This is a randomized, placebo-controlled, double-blind, double-dummy study to investigate the safety, tolerability, PK, and PD of subcutaneous (SC) doses of MET233 co-administered with MET097 in adult participants with a BMI of 27 to 45 kg/m2 (inclusive), including some participants with T2DM. For Part A, after the up to 4-week screening period, the study includes 1 dose and a 12-week safety follow-up after administration. For Part B and Part C, after the up to 4-week screening period, the study includes 12 once-weekly doses and an approximately 11-week safety follow-up after the last administration. Parts A and B will include only participants with overweight or obesity without type 2 diabetes. Part C will include participants with overweight or obesity who also have type 2 diabetes. For Part D, after the up to 4-week screening period, the study includes weekly and monthly (ie, every 4 weeks [QM]) and an approximate 11-week safety follow-up after last administration. For Part E, after the up to 4-week screening period, the study includes multiple dose QW-to-QM and an approximate 11-week safety followup after last administration. For Part G, after the up to 4-week screening period, the study includes multiple dose cohort of QW and QM and an approximate 11-week safety followup after last administration.

Inclusion Criteria:

• Adult males or females aged 18 to 75 years (inclusive) at the time of screening.

• BMI ≥27.0 kg/m2 and ≤38.0 kg/m2 (inclusive) at Screening for Parts A, B, and C, and ≥30.0 kg/m2 and ≤45.0 kg/m2 (inclusive) at Screening for Parts D and E. Have a BMI ≥27.0 kg/m2 and ≤45.0 kg/m2 (inclusive) at Screening for Parts G.

• Participants must be in generally stable health, as determined by the investigator based on medical history, physical examination (including vital signs), laboratory evaluations, and electrocardiogram (ECG).

  • Participants must have no clinically significant diseases or clinically significant findings on the physical examination (including vital signs), laboratory evaluations, and electrocardiogram (ECG).
  • Participants in Parts C must not have clinically significant diseases except type 2 diabetes mellitus (T2DM), sleep apnea, well-controlled hypertension, and/or dyslipidemia.
  • Participants in Parts E and G must not have any clinically significant diseases except hypertension, dyslipidemia, and/or a clinical diagnosis of sleep apnea.

• Willing and able to comply with all scheduled study visits, procedures, and required assessments.

• Women of childbearing potential must be willing to comply with protocol-specified contraceptive requirements and must not plan to become pregnant during the study.

Exclusion Criteria:

• Female who is lactating or who is pregnant according to the pregnancy test at Screening or on Day 1. Unwillingness or inability to comply with protocol-specified contraceptive requirements.
• Clinically significant abnormalities in laboratory results in the opinion of the investigator, increase risk or interfere with study participation.
• Seated blood pressure higher than 160/100 mmHg at the Screening visit or prior to the first study drug administration.
• Elevated resting pulse greater than 100 beats per minute at Screening visit or prior to the first study drug administration.
• Estimated glomerular filtration rate (eGFR) <80 mL/min at the Screening visit.
• Diagnosis of Type 1 diabetes.
• For Part A, Part B, Part D, Part E and Part G: Diagnosis of T2DM or glycated hemoglobin (HbA1c) > 6.4% or fasting plasma glucose >126 mg/dL at the Screening visit or history of taking any medications to lower glucose.
• For Part A, Part B and Part D: Participant reported weight-related comorbidity, including sleep apnea and cardiovascular disease.
• Use of prohibited prescription or non-prescription medications, supplements, or investigational products within protocol-defined washout periods.
• History or presence of clinically significant gastrointestinal, endocrine, respiratory, renal, hepatic, hematologic, neurologic, cardiovascular, psychiatric, immunologic, or other systemic diseases, except where explicitly permitted by the protocol.
• Personal or family history of medullary thyroid carcinoma, multiple endocrine neoplasia syndrome, pancreatitis, or pancreatic cancer.
• History of acute or chronic pancreatitis or pancreatic cancer.
• Participation in a weight loss program with or without pharmacotherapy during the 3 months prior to study administration or plans to do so.
• History of bariatric or weight-loss surgery.
• Clinically significant psychiatric illness that may interfere with study participation or safety.
• Screening assessments indicative of moderate to severe depression.
• History of drug or alcohol abuse or dependence within the past 2 years.

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.