Clinical Research Directory

Inclusion Criteria: Part A * Male and female participants aged 18 to 60 years * BMI 28 to 35 kg/m2 which has been stable (±5%) for the previous 3 to 6 months (based on participant self-report or medical records). For participants considered for enrollment in a cohort expansion, BMI 28 to 40 kg/ m2 will be allowed. * Healthy, in the opinion of the Investigator, as determined by prestudy medical history, physical examination, and clinical laboratory assessments Inclusion Criteria : Part B * Male and female participants aged 18 to 60 years * BMI 35 to 50 kg/m2 (inclusive) * Thyroid stimulating hormone is within normal range at Screening. May be on supplemental thyroid hormone as managed by their prescribing physician and stable within the last 60 days * Have Pre T2D or T2D Exclusion Criteria: Part A * History or presence of CV disease, including heart failure (New York Heart Association \[NYHA\] Class III or IV), myocardial infarction, angina, or clinically significant abnormal laboratory assessments * History or presence of thyroid disorders * Medical history or diagnosis of causes of liver disease * Use of any siRNA agent in the prior 12 months * Received an investigational agent within 90 days or 5 half-lives, whichever is longer, before the first dose of study drug or are in follow-up of another clinical study Exclusion Criteria: Part B * History of significant CV disease in the opinion of the Investigator. * Use of prescription medications (ie, anti-obesity or psychiatric medications) within 14 days or 7 half-lives (whichever is longer) before the first dose of study drug, except for allowed antihypertensive medications and statins. * Taking \>2 antihypertensive medications, or antihypertensive medication dose was changed in the 60 days prior to Screening. * Taking \>1 cholesterol-lowering medication, or cholesterol-lowering medication dose was changed in the 60 days prior to Screening. * Cohorts 1 and 2 (preT2D) only: use of any GLP-1 receptor agonists or dual incretin agonists within the 4 months prior to Screening. * Cohorts 4 and 5 (T2D) only: use of insulin or any medication that directly stimulates pancreatic insulin within the 60 days prior to Screening, including sulfonylureas, meglitinides, GLP-1 receptor agonists, dual incretin agonists, and DPP-4 inhibitors. * Use of any siRNA agent in the prior 12 months. * Received an investigational agent within 90 days or 5 half-lives, whichever is longer, before the first dose of study drug or are in follow-up of another clinical study.