Clinical trial NCT01481779 (phase 3, status: completed)
Conditions: diabetes mellitus, type 1
ICD codes: E10.65, E10.9, E10.21, E10.36, E10.41, E10.42, E10.44
Drugs: glargine, ly2605541, insulin lispro
SMILES: [Na+].[Na+].[O-]P([O-])(F)=O
Eligibility criteria:

        Inclusion Criteria:

          -  Have had diabetes mellitus for at least 1 year

          -  Have an hemoglobin A1c (HbA1c) value less than 12% according to the central laboratory
             at screening

          -  Have a body mass index (BMI) less than or equal to 35.0 kilograms per square meter
             (kg/m^2)

          -  Have been treated for at least 90 days prior to screening with the following:

               -  Insulin detemir, insulin glargine, or human insulin isophane suspension (NPH)
                  insulin in combination with premeal insulin,

               -  Self-mixed or premixed insulin regimens with any basal and bolus insulin
                  combination administered at least twice daily, or

               -  Continuous SC insulin infusion therapy

          -  This inclusion criterion applies to female participants:

               -  Are not breastfeeding

               -  Test negative for pregnancy at screening and randomization based on serum
                  pregnancy tests

               -  Do not intend to become pregnant during the study

               -  Have practiced a reliable method of birth control (for example, use of oral
                  contraceptives or levonorgestrel, diaphragms with contraceptive jelly, cervical
                  caps with contraceptive jelly, condoms with contraceptive foam, intrauterine
                  devices, partner with vasectomy, or abstinence) for at least 6 weeks prior to
                  screening

               -  Agree to continue to use a reliable method of birth control during the study, as
                  determined by the investigator (and for 2 weeks following the last dose of study
                  drug)

          -  Capable of and willing and desirous to do the following: adhere to a multiple daily
             injection regimen, inject insulin with a prefilled pen and perform Self-Monitored
             Blood Glucose (SMBG) and record keeping as required by this protocol, as determined by
             the investigator. Caregiver may be responsible for all of the above.

        Exclusion Criteria:

          -  Are using twice-daily insulin glargine having been inadequately controlled on
             once-daily dosed glargine prior to screening

          -  Have excessive insulin resistance defined as having received a total daily dose of
             insulin greater than 1.5 units per kilogram (units/kg) at the time of randomization

          -  Receiving any oral or injectable medication (other than metformin for treatment of
             polycystic ovarian disease) intended for the treatment of diabetes mellitus other than
             insulins in the 90 days prior to screening

          -  Lipid-lowering medications:

               -  Are using niacin preparations as a lipid-lowering medication and/or bile acid
                  sequestrants within 90 days prior to screening or are using lipid-lowering
                  medication at a dose that has not been stable for greater than or equal to 90
                  days prior to screening

               -  If a participant has not been on a stable dose of lipid-lowering medication for
                  greater than or equal to 90 days prior to screening, the site should wait to
                  screen the participant. If the results of the screening laboratory tests require
                  a change to the participant's current lipid-lowering medication or initiation of
                  lipid-lowering medication, it is acceptable to change the lipid-lowering
                  medication for the participant and to have the participant return greater than or
                  equal to 90 days later to complete some of the screening procedures again

          -  Have fasting hypertriglyceridemia (defined as greater than 4.5 millimoles per liter
             [mmol/L], greater than 400 milligrams per deciliter [mg/dL]) at screening, as
             determined by the central laboratory

          -  Have had more than 1 episode of severe hypoglycemia (defined as requiring assistance
             due to neurologically disabling hypoglycemia as determined by the investigator) within
             6 months prior to entry into the study

          -  Have had 2 or more emergency room visits or hospitalizations due to poor glucose
             control (hyperglycemia or diabetic ketoacidosis) in the past 6 months

          -  Cardiovascular: have cardiac disease with functional status that is New York Heart
             Association Class III or IV (per New York Heart Association Cardiac Disease
             Classification)

          -  Renal: Have a history of renal transplantation or are currently receiving renal
             dialysis or have serum creatinine greater than 2.5 mg/dL

          -  Hepatic: Have obvious clinical signs or symptoms of liver disease (excluding
             non-alcoholic fatty liver disease [NAFLD]), acute or chronic hepatitis, non-alcoholic
             steatohepatitis (NASH), or elevated liver enzyme measurements as indicated below:

               -  Total bilirubin greater than or equal to 2 times the upper limit of normal (ULN)
                  as defined by the central laboratory,

               -  Alanine aminotransferase (ALT)/(serum glutamic pyruvic transaminase (SGPT)
                  greater than 2.5 times ULN as defined by the central laboratory, or

               -  Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT)
                  greater than 2.5 times ULN as defined by the central laboratory.

          -  Malignancy: 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 an increased risk for developing cancer or a
             recurrence of cancer in the opinion of the investigator

          -  Allergy: Have known hypersensitivity or allergy to any of the study insulins or their
             excipients

          -  Hematologic: Have had a blood transfusion or severe blood loss within 3 months prior
             to screening or have known hemoglobinopathy, hemolytic anemia, sickle cell anemia, or
             any other traits of hemoglobin abnormalities known to interfere with the HbA1c
             measurement

          -  Glucocorticoid therapy: Receiving chronic (lasting longer than 14 consecutive days)
             systemic glucocorticoid therapy (excluding topical , intraocular, intranasal, and
             inhaled preparations) or have received such therapy within 8 weeks immediately before
             screening with the exception of replacement therapy for adrenal insufficiency

          -  Diagnosed clinically significant diabetic autonomic neuropathy, in the opinion of the
             investigator

          -  Have any other condition (including known drug or alcohol abuse or psychiatric
             disorder including eating disorder) that precludes the participant from following and
             completing the protocol