A Study to Evaluate ALN-4324 in Overweight to Obese Healthy Volunteers and in Overweight to Obese Patients With T2DM

• ALN-4324 (Drug): ALN-4324 will be administered subcutaneously (SC)
• Placebo (Drug): Placebo will be administered SC

Primary outcomes

• Part A: Frequency of Adverse Events (AEs) [Up to 9 months]
• Part B: Frequency of Adverse Events [Up to 12 months]

Secondary outcomes

• Part A: Area Under the Plasma Concentration-time Curve (AUC) of ALN-4324 in Plasma [Predose and up to 3 days postdose]
• Part A: Maximum Observed Plasma Concentration (Cmax) of ALN-4324 in Plasma [Predose and up to 3 days postdose]
• Part A: Time to Maximum Plasma Concentration (Tmax) of ALN-4324 in Plasma [Predose and up to 3 days postdose]
• Part A: Fraction of ALN-4324 excreted in urine [Predose and up to 24 hours postdose (fe)]
• Part B: Change from Baseline in HbA1c [Baseline up to 6 months]
• Part B: Response to Glucose Tolerance Test [Predose and up to 2 hours postdose]
• Part B: Concentrations of ALN-4324 in Plasma [Predose and up to 4 hours postdose]

Sex: All, ages: 18 Years to 75 Years, accepts healthy volunteers

Inclusion Criteria:

Part A:

* Has a body mass index (BMI) of ≥27 kg/m\^2 and <40 kg/m\^2

Part B:

* Is an adult patient with a confirmed diagnosis of T2DM
* Has a hemoglobin A1c (HbA1c) ≥7% to <10.5%
* Has a BMI of ≥25 kg/m\^2 and <45 kg/m\^2
* Is on a stable dose of either metformin or metformin and a sodium-glucose cotransporter 2 inhibitor (SGLT2i)

Exclusion Criteria:

Part A:

* Has known human immunodeficiency virus (HIV) infection; or known current or chronic hepatitis C virus or hepatitis B virus infection

Part B:

* Receiving therapies for chronic weight management or antidiabetic medications other than metformin and SGLT2i

Note: other protocol defined inclusion/exclusion criteria apply

• Medical Director, Study director, Alnylam Pharmaceuticals