Overview

This study is being done to learn how the study medicine affects the body and how safe it is for people who take it. The researchers will look at a number of health tests, including blood tests such as calcitonin, amylase, and lipase, because similar medicines have sometimes caused changes in these tests.

This study is seeking participants who are:

• Adults who are obese or overweight with weight-related health conditions, and
• Meet health and other checks assessed by the study doctor.

The study team will give a single dose of the study treatment at the clinic to the participants. At each study visit, blood samples will be collected, vital signs will be checked, and the study team will ask about any reactions or health changes. Vital signs are basic measurements that show how well the body is working. They help the study team quickly understand a participant's overall health. These usually include body temperature, heart rate, breathing rate, and blood pressure.

The study involves multiple clinic visits at a study site over the length of the study. The information collected will help researchers understand how the study medicine works and whether it is safe.

Eligibility

Key Inclusion Criteria:

• Participants 18 years of age or older at Screening who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and ECGs.
• BMI of 27-45 kg/m2 ; and a total body weight \>50 kg (110 lb).
• For Japanese participants only: BMI of 20-45 kg/m2 and a total body weight \>50 kg (110 lb) and must have 4 biological Japanese grandparents who were born in Japan.

Key Exclusion Criteria:

• Pregnant or breastfeeding women, or those planning pregnancy during the study.
• Clinically significant medical conditions including hematologic, renal, endocrine, pulmonary, gastrointestinal (including pancreatitis, gallbladder disease, clinically relevant gastric emptying disorders), cardiovascular, hepatic, psychiatric, neurologic, or severe allergic diseases.
• Personal or first-degree family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia type 2 (MEN2), or suspected MTC.
• Active or recent suicidal ideation in the past year, suicidal behavior within the past 5 years, or any psychiatric condition that increases risk in the investigator's judgment.
• Clinically significant gastric emptying abnormality or chronically taking drugs that directly affect GI motility.
• Acute gastrointestinal symptoms at screening or Day -1.
• Known hypersensitivity to PF-08653944, GLP-1 receptor agonists, or any excipients.
• Prior participation in any study involving PF-08653944 (formerly MET097) with at least one dose received.