A Study of MET233 in Combination With MET097 in Individuals With Obesity or Overweight With or Without Diabetes

Prior treatment

• 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.
• Use of prohibited prescription or non-prescription medications, supplements, or investigational products within protocol-defined washout periods.
• Participation in a weight loss program with or without pharmacotherapy during the 3 months prior to study administration or plans to do so.

Other illness

• Diagnosis of Type 1 diabetes.
• For Part A, Part B and Part D: Participant reported weight-related comorbidity, including sleep apnea and cardiovascular disease.
• 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.
• History of bariatric or weight-loss surgery.
• Clinically significant psychiatric illness that may interfere with study participation or safety.
• History of drug or alcohol abuse or dependence within the past 2 years.

Lab values

• Clinically significant abnormalities in laboratory results in the opinion of the investigator, increase risk or interfere with study participation.
• Estimated glomerular filtration rate (eGFR) \<80 mL/min at the Screening visit.
• 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.

Other

• 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.
• Screening assessments indicative of moderate to severe depression.

• 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.