A Study to Compare the Effect of a Double Dose of Two Long-acting Insulin Therapies in Participants With Type 2 Diabetes
Condition: Type 2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Insulin Peglispro; Insulin Glargine
Intervention description: Administered SQ; Administered SQ
Intervention MeSH terms: Insulin; Insulin, Globin Zinc; Insulin Glargine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Enrollment: 68.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No

Summary:

      The primary purpose of this study is to compare the effect of a double dose of a study drug
      known as insulin peglispro to a double dose of insulin glargine in participants who have type
      2 diabetes. Participants will be treated with study insulin daily, in two 4-week study
      periods. Each participant will receive insulin peglispro during one treatment period and
      insulin glargine during the other treatment period.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Have type 2 diabetes mellitus (T2DM), based on the World Health Organization (WHO)
             classification, for ≥1 year.

          -  Use any type of basal insulin (except degludec), including once-or twice-daily human
             insulin neutral protamine Hagedom (NPH), insulin detemir, or insulin glargine.

          -  Have hemoglobin A1c (HbA1c) levels ≤9.0% according to local laboratory testing at
             screening.

          -  Have body mass index (BMI) ≤40.0 kilograms/square meter (kg/m^2).

          -  Have been treated with stable doses of insulin for at least 30 days before screening
             with:

               -  Basal insulin with daily doses ±30% of mean during the last 4 weeks.

               -  Doses of a basal insulin must be between 0.3 unit/kg/day and 1 unit/kg/day.

          -  If on metformin, thiazolidinediones (TZDs), sodium glucose co-transporter 2 (SGLT-2)
             inhibitors, or dipeptidyl peptidase (DPP4) inhibitors, must be on stable doses for the
             last 30 days.

        Exclusion Criteria:

          -  Are using prandial, self-mixed, or premixed insulin. Participants using prandial
             insulin may be switched to everyday (qd) glargine if investigator judges that the
             participant will still meet fasting glucose requirements for randomization.

          -  Are using insulin pump therapy.

          -  Have excessive insulin resistance: Defined as >1.0 unit/kg/day as baseline treatment.

          -  If being treated with sulfonylureas (SUs) before screening, then must have SUs washed
             out between screening and randomization.

          -  Use any of these concomitant medications: morphine, codeine, antidiuretics,
             glucagon-like peptide-1 (GLP-1) receptor agonists (for example, exenatide, exenatide
             once weekly, lixisenatide or liraglutide), or pramlintide, used concurrently or within
             90 days before screening.

          -  Have hypoglycemia unawareness, defined as confirmed by laboratory test results or by
             historical episodes of hypoglycemia <54 mg/dL (3.0 mmol/L) without symptoms.

          -  Have fasting hypertriglyceridemia >400 mg/dL (>4.5 mmol/L) at screening, as determined
             by the local laboratory.

          -  Have had any episode of severe hypoglycemia (defined by requiring assistance due to
             neurologically disabling hypoglycemia) within 6 months before entry into the study.

          -  Have had 2 or more emergency room visits or hospitalizations due to poor glucose
             control in the past 6 months.

          -  Have had a previous clinically significant episode of ketoacidosis as determined by
             the investigator (ketone bodies at fasting and without acidosis is acceptable) in the
             past 6 months.

          -  Have history of renal transplantation, are currently receiving renal dialysis, or have
             estimated Glomerular Filtration Rate (eGFR) <60 milliliters/minute.

          -  Have obvious clinical signs or symptoms of liver disease (excluding nonalcoholic fatty
             liver disease), acute or chronic hepatitis, nonalcoholic steatohepatitis, or elevated
             liver enzyme measurements.

          -  Have active or untreated malignancy, have been in remission from clinically
             significant malignancy (other than basal cell or squamous cell skin cancer) for less
             than 5 years, or are at increased risk for developing cancer or a recurrence of cancer
             in the opinion of the investigator.