Study of Human Regular U-500 Insulin in Adult Participants With Type 2 Diabetes

Major Inclusion Criteria:

- Have type 2 diabetes mellitus (World Health Organization [WHO] Classification of
Diabetes)

- Have a body mass index (BMI) ≥25 kilogram per square meter (kg/m^2)

- Have Glycated Hemoglobin A1c (HbA1c) ≥7.5% and ≤12.0%, as measured by the central
laboratory at entry

- Current U-100 insulin/analogue users on >200 and ≤600 units per day for ≥3 months at
study entry and reconfirmed at randomization

- Have a history of stable body weight for at least 3 months prior to study entry

- Concomitant medications may include metformin (MET), dipeptidyl peptidase-4 (DPP-4)
inhibitors approved for use with insulin at time of study entry (for example,
sitagliptin, saxagliptin, and linagliptin), pioglitazone, and/or sulfonylureas
(SUs)/glinides (repaglinide or nateglinide). Participant's oral antihyperglycemic
drug (OAD) dose(s) must have been stable for ≥3 months

Major Exclusion Criteria:

- Have type 1 diabetes mellitus or other types of diabetes mellitus apart from type 2
diabetes mellitus

- Have obvious clinical signs or symptoms of liver disease, acute or chronic hepatitis,
or alanine aminotransferase or aspartate aminotransferase levels ≥3 times the upper
limit of the reference range

- Have chronic kidney disease stage 4 and higher or history of renal transplantation

- Have history of more than 1 episode of severe hypoglycemia within the 6 months prior
to study entry

- Have received insulin by continuous subcutaneous insulin infusion in the 3 months
prior to study entry

- Have received U-500R in the 3 months prior to study entry

- Have had a blood transfusion or severe blood loss within 3 months prior to study
entry or have known hemoglobinopathy, hemolytic anemia, or sickle cell anemia

- Are taking chronic systemic glucocorticoid therapy or have received such therapy
within the 4 weeks immediately prior to study entry

- Have an irregular sleep/wake cycle

- Have used rosiglitazone, once- or twice-daily glucagon-like peptide-1 (GLP-1)
receptor agents, pramlintide, or other injectable or oral antihyperglycemic therapy
not listed in the inclusion criteria in the 3 months prior to study entry.
Participants may not have used once-weekly GLP-1 receptor agents in the 4 months
prior to study entry

- Have used any weight loss drugs in the 3 months prior to study entry

- Have a history of bariatric surgery

- Have a history of malignancy other than basal cell or squamous cell skin cancer

- Have New York Heart Association (NYHA) Class III or IV per NYHA Cardiac Disease
Functional Classification

- Are breastfeeding or pregnant, or intend to become pregnant during the course of the
study, or are sexually active women of childbearing potential not actively practicing
birth control by a method determined by the investigator to be medically acceptable