This is a randomized, double-blind,placebo-controlled phase I clinical study.The main purpose is to assess the safety and tolerability of single subcutaneous administration of HS-20136-2 injection in healthy participants.

This is a phase I, double-blind, randomised, placebo-controlled trial to assess the safety and tolerability of HS-20136-2 in healthy participants. We enrolled adults (aged 18-65 years, both inclusive) with body-mass index [BMI] ≥25 kg/m2 and ≤35 kg/m2 in Australia. Eligible participants were randomly assigned to receive a single dose subcutaneous injection of HS-20136-2 or placebo. The primary endpoint is：

1. Incidence, severity, and relationship to the investigational products of adverse events (AEs), serious adverse events (SAEs), and AEs leading to withdrawal from the study;
2. Changes in laboratory tests (hematology, urinalysis, blood biochemistry, coagulation function, etc.), vital signs, ECG results, etc., before and after administration.

Inclusion Criteria:

1. Participants who are able to sufficiently understand the study content, process, and potential adverse reactions, and voluntarily sign the informed consent form;
2. Healthy men and women aged 18-65 years (inclusive);
3. Body weight ≥ 50 kg (male) or ≥ 45 kg (female) and body mass index (BMI) within the range of 25-35 (inclusive) [BMI = body weight/body height2 (kg/m2)];

Exclusion Criteria:

1. Pregnant or lactating women;
2. Participants with a history of cardiovascular, respiratory, hepatic, renal, digestive tract, mental, neurological, hematological, immune, and metabolic abnormalities (such as unexplained recurrent hypoglycemia) and other diseases, and not suitable for the study as assessed by the investigator, such as: Childhood asthma (resolved),Depression (non-hospitalised, but potentially medicated in the past), Migraine, etc.
3. Glycosylated hemoglobin A1c (HbA1c) > 6.5% or fasting blood glucose ≤ 3.9 mmol/L (70 mg/dL) or ≥ 6.1 mmol/L (110 mg/dL) during the screening period;
4. The alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin (TBIL) > 1.5 × ULN during the screening period (except for cases of known Gilbert's Syndrome);
5. Participating in any clinical study involving drugs or medical devices (except for those not receiving an investigational drug or investigational device) within 3 months before screening or 5 half-lives (whichever is longer) before screening, or currently participating in a clinical trial;
6. Treatment with systemic steroids, immunomodulators, or chemotherapy within 3 months before screening or likely to receive them during the study;
7. Known severe allergic disease, or known allergies to GLP-1R agonists or Retatrutide, or allergic constitution (allergies to various drugs and foods);
8. With concomitant diseases that may significantly affect the absorption of drugs or nutrients as judged by the investigator, such as clinically significant gastrointestinal diseases (e.g., active inflammatory bowel disease) and symptoms of gastrointestinal disorders; or any condition that might affect the absorption of drugs, such as subtotal or total gastrectomy, sleeve gastrectomy, gastric bypass surgery, and resection of any intestinal area;
9. History of confirmed chronic pancreatitis or idiopathic acute pancreatitis, or serum amylase or lipase greater than the upper limit of normal at screening. A participant with a history of acute pancreatitis caused by gallstones may be included in the study if the participant has a cholecystectomy to resolve the problem;
10. Have a history of symptomatic gallbladder disease within the past 2 years, defined by the presence of gallstones on an imaging study and abdominal pain attributed to the gallstones by the participant's physician; subjects who had a procedure to remove the gallstones and/or the gallbladder (cholecystectomy), with no long-term complications, are eligible for participation as long as the procedure was completed at least 3 months prior to screening;
11. Diet or weight loss treatment within 3 months prior to administration (regardless of the reason) or having body weight change of more than 5% or a significant change in living habits within 3 months prior to administration;
12. Other reasons for exclusion, as determined by the investigator.