Safety, Tolerability, and Pharmacodynamics of IONIS-DGAT2Rx in Adult Patients With Type 2 Diabetes

Inclusion Criteria: * Must have given written informed consent and be able to comply with all study requirements. * Males or females aged 18-75, inclusive, at the time of Informed Consent. * Females must be non-pregnant and non-lactating, and either surgically sterile or post- menopausal. * Males must be surgically sterile, abstinent or using an acceptable contraceptive method. * Body mass index (BMI) ≥ 27.0 - ≤ 39.0 kilograms per square meter (kg/m\^2). * Diagnosis of Type 2 Diabetes Mellitus with an Hemoglobin A1C (HbA1c) ≥7.3% and ≤9.5% at screening. * Must have been on a stable dose of Oral Antidiabetic Therapy for a minimum of 3 months prior to Screening. * ≥ 10% liver fat prior to randomization assessed by MRI-PDFF. * Stable body weight for at least 3 months before screening. Exclusion Criteria: * Clinically-significant abnormalities in medical history or physical examination. * Clinically-significant abnormalities in screening laboratory values that would render a participant unsuitable for inclusion, per Sponsor. * Evidence of uncorrected hypothyroidism or hyperthyroidism results at Screening. * History of solid organ transplantation or renal dialysis. * Clinically-significant complications of diabetes. * Treatment with another Study Drug, biological agent, or device within one-month of screening. * Known history or evidence of liver disease with a positive test for human immunodeficiency virus (HIV), Hepatitis C virus (HCV), or chronic Hepatitis B virus (HBV), or chronic liver disease other than NASH. * Recent history of, or current drug or alcohol abuse. * Current use of concomitant medications known to significantly impact body weight or that may cause liver toxicity, per Investigator * Use of anticoagulant/Antiplatelet agents unless the dose has been stable for 4 weeks prior to the first dose of study drug\] * Use of non-steroidal anti-inflammatory drug nimesulide or any other drug influencing coagulation (except lose-dose aspirin). * Use of obeticholic acid or ursodeoxycholic acid * Considered unsuitable for inclusion by the Principal Investigator