Study of Human Regular U-500 Insulin in Adult Participants With Type 2 Diabetes
Condition: Diabetes Mellitus, Type 2
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Human Regular U-500 Insulin
Intervention MeSH terms: Insulin
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 325.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      The main purpose of this study is to compare the effectiveness of Human Regular U-500 Insulin
      three times a day versus twice a day.
    

Eligibility criteria:

        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