Diabetes Mellitus, Type 2
Conditions
Brief summary
This study is designed to look at how best to start and then gradually intensify (as needed) the insulin lispro premix regimen in type 2 diabetes patients who consume a light breakfast.
Interventions
DRUGInsulin Glargine
patient glucose-level dependent, injection, as needed per patient glucose level, 48 weeks
DRUGInsulin Lispro Premix (mid-mixture and low-mixture)
patient glucose level dependent, injection, as needed per patient glucose level, 48 weeks
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
30 Years to 74 Years
Healthy volunteers
No
Inclusion criteria
* Diabetes Mellitus, Type 2 * have been receiving metformin plus at least one other oral antihyperglycemic medication (OAM) (sulfonylurea or Thiazolidinedione \[TZD\]) without insulin, for at least 90 days prior to Visit 1 * glycosylated hemoglobin (HbA1c) greater than or equal to 7.0% and less than 11.0% * regularly consume a light breakfast (less than 15% of total daily calorie intake) * capable and willing to follow the protocol * give written consent
Exclusion criteria
* are taking a TZD whose country label does not allow in combination with insulin * are taking any glucose-lowering agents (other than specified in the inclusion criteria above) * have a body mass index greater than 40 kg/m\^2 * have a history of severe hypoglycemia in past 24 weeks * are pregnant or may become pregnant * women who are breastfeeding * have significant cardiac disease * have significant renal or liver disease * undergoing therapy for a malignancy * contraindications to study medications * have an irregular sleep/wake cycle
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Baseline Adjusted Glycosylated Hemoglobin (HbA1c) at Endpoint | 48 weeks | Least Squares Mean (LSMean) values were adjusted based on a fixed effect linear regression model: HbA1c = Treatment + Country + HbA1c baseline value + Ramadan holiday between Visit 10 (Week 36) and Visit 12 (Week 48) (yes/no) in per-protocol (PP) population. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| HbA1c Over Time | 16 weeks, 32 weeks, and 48 weeks | Least Squares Mean (LSMean) values were adjusted based on a mixed effect linear regression model with a participant specific random effect: HbA1c = Treatment + Country + HbA1c baseline value + Ramadan holiday between Visit 10 (Week 36) and Visit 12 (Week 48) (yes/no) + visit + visit\*treatment in Full Analysis Set (FAS) Population. |
| Percentage of Patients Achieving HbA1c Less Than or Equal to 6.5% and Less Than or Equal to 7% Over Time | 16 weeks, 32 weeks and 48 weeks | — |
| 7-point Self-monitored Blood Glucose Profiles | 16 weeks, 32 weeks and 48 weeks | — |
| Mean Postprandial Blood Glucose Values | Baseline, 16 weeks, 32 weeks and 48 weeks | Mean postprandial blood glucose values were assessed using GlycoMark, which is an FDA-approved blood test measuring levels of 1,5 anhydroglucitol (1,5 AG) in serum or plasma. When 1,5 AG values decrease, serum glucose levels increase. |
| Percentage of Participants Using Each Possible Final Insulin Regimen | 48 weeks | Insulin Regimens: Lispro: Mid-Mix (MM) before noon; Low-Mix (LM) before evening (PM); MM before noon+LM before PM; LM before morning (AM)+MM before noon + LM before PM; MM before AM +MM before noon+LM before PM Glargine: Glargine once a day (QD); Glargine QD + 1 Lispro (noon or PM); Glargine QD + 2 Lispro (noon and PM); Glargine QD + 3 Lispro. |
| Body Weight Change From Baseline to Endpoint | baseline, 48 weeks | — |
| Incidence of All Self-reported Hypoglycemic Episodes | Baseline to 48 weeks | Percentage of participants with self-reported hypoglycemic episodes at any time during the study. A hypoglycemic episode is defined as any time a participant feels that he/she is experiencing a sign or symptom that is associated with hypoglycemia, or has a blood glucose level of ≤70 mg/dL (3.9 mmol/L) (Roche plasma glucose) or ≤75 mg/dL (4.2 mmol/L) (IFCC Plasma Values), even if it was not associated with signs, symptoms, or treatment consistent with current guidelines (ADA 2005). |
| Rate Per 30 Days of All Self-reported Hypoglycemic Episodes | Baseline to 48 weeks | The hypoglycemia rate between two visits will be calculated as the total number of episodes between the two visits divided by the number of days between the visits, and then multiplied by 30 days (rate per patient per 30 days). |
| Number of Participants With Adverse Events | Baseline to 48 weeks | A summary of serious adverse events (SAEs) and all other non-serious treatment-emergent adverse events (TEAE) is located in the Reported Adverse Event Module. TEAEs are defined as events that are newly reported after randomization or reported to worsen in severity from baseline. |
| Mean Daily Total, Basal and Prandial Insulin Dose | 16 weeks, 32 weeks and 48 weeks | — |
Countries
Canada, Egypt, India, Mexico, Portugal, Romania, Spain, Turkey (Türkiye)
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Glargine Glargine +/- 1,2 or 3 injections of insulin lispro plus oral antihyperglycemic medications (OAMs) | 173 |
| Premix Insulin Lispro Premixed Insulin Lispro (mid-mixture or low-mixture)1,2 or 3 injections plus OAMs | 171 |
| Total | 344 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 3 |
| Overall Study | Lost to Follow-up | 6 | 10 |
| Overall Study | Physician Decision | 8 | 0 |
| Overall Study | Protocol Violation | 10 | 8 |
| Overall Study | Sponsor decision | 8 | 6 |
| Overall Study | Withdrawal by Subject | 7 | 6 |
Baseline characteristics
| Characteristic | Total | Premix Insulin Lispro | Glargine |
|---|---|---|---|
| Age Continuous | 54.29 years STANDARD_DEVIATION 8.77 | 54.33 years STANDARD_DEVIATION 8.944 | 54.24 years STANDARD_DEVIATION 8.621 |
| Glycosylated Hemoglobin (HbA1c) | 9.02 percent glycosylated hemoglobin STANDARD_DEVIATION 0.966 | 8.98 percent glycosylated hemoglobin STANDARD_DEVIATION 0.945 | 9.07 percent glycosylated hemoglobin STANDARD_DEVIATION 0.988 |
| Race/Ethnicity, Customized African | 3 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Caucasian | 198 Participants | 101 Participants | 97 Participants |
| Race/Ethnicity, Customized East Asian | 21 Participants | 10 Participants | 11 Participants |
| Race/Ethnicity, Customized Hispanic | 84 Participants | 40 Participants | 44 Participants |
| Race/Ethnicity, Customized West Asian | 38 Participants | 19 Participants | 19 Participants |
| Region of Enrollment Brazil | 13 participants | 5 participants | 8 participants |
| Region of Enrollment Canada | 7 participants | 4 participants | 3 participants |
| Region of Enrollment Egypt | 64 participants | 33 participants | 31 participants |
| Region of Enrollment India | 58 participants | 28 participants | 30 participants |
| Region of Enrollment Mexico | 71 participants | 33 participants | 38 participants |
| Region of Enrollment Portugal | 15 participants | 8 participants | 7 participants |
| Region of Enrollment Romania | 50 participants | 25 participants | 25 participants |
| Region of Enrollment Spain | 40 participants | 22 participants | 18 participants |
| Region of Enrollment Turkey | 26 participants | 13 participants | 13 participants |
| Sex: Female, Male Female | 176 Participants | 84 Participants | 92 Participants |
| Sex: Female, Male Male | 168 Participants | 87 Participants | 81 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 52 / 169 | 53 / 173 |
| serious Total, serious adverse events | 7 / 169 | 3 / 173 |
Outcome results
Primary
Baseline Adjusted Glycosylated Hemoglobin (HbA1c) at Endpoint
Least Squares Mean (LSMean) values were adjusted based on a fixed effect linear regression model: HbA1c = Treatment + Country + HbA1c baseline value + Ramadan holiday between Visit 10 (Week 36) and Visit 12 (Week 48) (yes/no) in per-protocol (PP) population.
Time frame: 48 weeks
Population: PP Population=All participants who were randomized and met following criteria during study:~* no violations of Inclusion/Exclusion Criteria~* no early study discontinuation~* compliant with treatment~* received no other antihyperglycemic medication than allowed in Protocol, and have not been on systemic glucocorticoids for \>14 consecutive days.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Glargine | Baseline Adjusted Glycosylated Hemoglobin (HbA1c) at Endpoint | 7.55 percent glycosylated hemoglobin |
| Premix Insulin Lispro | Baseline Adjusted Glycosylated Hemoglobin (HbA1c) at Endpoint | 7.40 percent glycosylated hemoglobin |
95% CI: [-0.42, 0.13]
Secondary
7-point Self-monitored Blood Glucose Profiles
Time frame: 16 weeks, 32 weeks and 48 weeks
Population: Full Analysis Set: All participants who enrolled in this study, completed Screening, were randomized to one of the study treatments, and had at least one post baseline measurement for the dependent variable, according to intent-to-treat (ITT) principles.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Glargine | 7-point Self-monitored Blood Glucose Profiles | Week 16 Before Breakfast (n=142, n=145) | 6.94 millimoles per Liter (mmol/L) | Standard Error 0.17 |
| Glargine | 7-point Self-monitored Blood Glucose Profiles | Week 32 Before Breakfast (n=126, n=130) | 6.65 millimoles per Liter (mmol/L) | Standard Error 0.14 |
| Glargine | 7-point Self-monitored Blood Glucose Profiles | Week 48 Before Breakfast (n=123, n=130) | 6.79 millimoles per Liter (mmol/L) | Standard Error 0.15 |
| Glargine | 7-point Self-monitored Blood Glucose Profiles | Week 16 After Breakfast (n=136, n=138) | 9.12 millimoles per Liter (mmol/L) | Standard Error 0.25 |
| Glargine | 7-point Self-monitored Blood Glucose Profiles | Week 32 After Breakfast (n=123, n=127) | 8.65 millimoles per Liter (mmol/L) | Standard Error 0.24 |
| Glargine | 7-point Self-monitored Blood Glucose Profiles | Week 48 After Breakfast (n=120, n=129) | 8.88 millimoles per Liter (mmol/L) | Standard Error 0.23 |
| Glargine | 7-point Self-monitored Blood Glucose Profiles | Week 16 Before Lunch (n=143, n=145) | 7.33 millimoles per Liter (mmol/L) | Standard Error 0.21 |
| Glargine | 7-point Self-monitored Blood Glucose Profiles | Week 32 Before Lunch (n=128, n=132) | 7.00 millimoles per Liter (mmol/L) | Standard Error 0.19 |
| Glargine | 7-point Self-monitored Blood Glucose Profiles | Week 48 Before Lunch (n=121, n=129) | 7.14 millimoles per Liter (mmol/L) | Standard Error 0.2 |
| Glargine | 7-point Self-monitored Blood Glucose Profiles | Week 16 After Lunch (n=138, n=140) | 9.32 millimoles per Liter (mmol/L) | Standard Error 0.25 |
| Glargine | 7-point Self-monitored Blood Glucose Profiles | Week 32 After Lunch (n=127, n=130) | 8.34 millimoles per Liter (mmol/L) | Standard Error 0.23 |
| Glargine | 7-point Self-monitored Blood Glucose Profiles | Week 48 After Lunch (n=120, n=126) | 8.58 millimoles per Liter (mmol/L) | Standard Error 0.24 |
| Glargine | 7-point Self-monitored Blood Glucose Profiles | Week 16 Before Dinner (n=143, n=145) | 7.84 millimoles per Liter (mmol/L) | Standard Error 0.21 |
| Glargine | 7-point Self-monitored Blood Glucose Profiles | Week 32 Before Dinner (n=129, n=132) | 7.31 millimoles per Liter (mmol/L) | Standard Error 0.19 |
| Glargine | 7-point Self-monitored Blood Glucose Profiles | Week 48 Before Dinner (n=120, n=129) | 7.55 millimoles per Liter (mmol/L) | Standard Error 0.21 |
| Glargine | 7-point Self-monitored Blood Glucose Profiles | Week 16 After Dinner (n=140, n=141) | 9.68 millimoles per Liter (mmol/L) | Standard Error 0.26 |
| Glargine | 7-point Self-monitored Blood Glucose Profiles | Week 32 After Dinner (n=128, n=131) | 8.64 millimoles per Liter (mmol/L) | Standard Error 0.23 |
| Glargine | 7-point Self-monitored Blood Glucose Profiles | Week 48 After Dinner (n=120, n=126) | 8.87 millimoles per Liter (mmol/L) | Standard Error 0.22 |
| Glargine | 7-point Self-monitored Blood Glucose Profiles | Week 16 at 0300 Hours (n=114, n=120) | 7.34 millimoles per Liter (mmol/L) | Standard Error 0.33 |
| Glargine | 7-point Self-monitored Blood Glucose Profiles | Week 32 at 0300 Hours (n=105, n=106) | 6.94 millimoles per Liter (mmol/L) | Standard Error 0.32 |
| Glargine | 7-point Self-monitored Blood Glucose Profiles | Week 48 at 0300 Hours (n=104, n=107) | 6.94 millimoles per Liter (mmol/L) | Standard Error 0.32 |
| Premix Insulin Lispro | 7-point Self-monitored Blood Glucose Profiles | Week 32 After Lunch (n=127, n=130) | 8.69 millimoles per Liter (mmol/L) | Standard Error 0.22 |
| Premix Insulin Lispro | 7-point Self-monitored Blood Glucose Profiles | Week 16 Before Breakfast (n=142, n=145) | 7.36 millimoles per Liter (mmol/L) | Standard Error 0.17 |
| Premix Insulin Lispro | 7-point Self-monitored Blood Glucose Profiles | Week 16 at 0300 Hours (n=114, n=120) | 7.22 millimoles per Liter (mmol/L) | Standard Error 0.31 |
| Premix Insulin Lispro | 7-point Self-monitored Blood Glucose Profiles | Week 32 Before Breakfast (n=126, n=130) | 7.20 millimoles per Liter (mmol/L) | Standard Error 0.14 |
| Premix Insulin Lispro | 7-point Self-monitored Blood Glucose Profiles | Week 48 After Lunch (n=120, n=126) | 8.34 millimoles per Liter (mmol/L) | Standard Error 0.23 |
| Premix Insulin Lispro | 7-point Self-monitored Blood Glucose Profiles | Week 48 Before Breakfast (n=123, n=130) | 6.94 millimoles per Liter (mmol/L) | Standard Error 0.15 |
| Premix Insulin Lispro | 7-point Self-monitored Blood Glucose Profiles | Week 32 After Dinner (n=128, n=131) | 8.50 millimoles per Liter (mmol/L) | Standard Error 0.23 |
| Premix Insulin Lispro | 7-point Self-monitored Blood Glucose Profiles | Week 16 After Breakfast (n=136, n=138) | 9.92 millimoles per Liter (mmol/L) | Standard Error 0.25 |
| Premix Insulin Lispro | 7-point Self-monitored Blood Glucose Profiles | Week 16 Before Dinner (n=143, n=145) | 7.92 millimoles per Liter (mmol/L) | Standard Error 0.21 |
| Premix Insulin Lispro | 7-point Self-monitored Blood Glucose Profiles | Week 32 After Breakfast (n=123, n=127) | 9.16 millimoles per Liter (mmol/L) | Standard Error 0.23 |
| Premix Insulin Lispro | 7-point Self-monitored Blood Glucose Profiles | Week 48 at 0300 Hours (n=104, n=107) | 6.57 millimoles per Liter (mmol/L) | Standard Error 0.31 |
| Premix Insulin Lispro | 7-point Self-monitored Blood Glucose Profiles | Week 48 After Breakfast (n=120, n=129) | 8.94 millimoles per Liter (mmol/L) | Standard Error 0.22 |
| Premix Insulin Lispro | 7-point Self-monitored Blood Glucose Profiles | Week 32 Before Dinner (n=129, n=132) | 7.39 millimoles per Liter (mmol/L) | Standard Error 0.18 |
| Premix Insulin Lispro | 7-point Self-monitored Blood Glucose Profiles | Week 16 Before Lunch (n=143, n=145) | 7.66 millimoles per Liter (mmol/L) | Standard Error 0.21 |
| Premix Insulin Lispro | 7-point Self-monitored Blood Glucose Profiles | Week 48 After Dinner (n=120, n=126) | 8.09 millimoles per Liter (mmol/L) | Standard Error 0.21 |
| Premix Insulin Lispro | 7-point Self-monitored Blood Glucose Profiles | Week 32 Before Lunch (n=128, n=132) | 7.25 millimoles per Liter (mmol/L) | Standard Error 0.19 |
| Premix Insulin Lispro | 7-point Self-monitored Blood Glucose Profiles | Week 48 Before Dinner (n=120, n=129) | 7.19 millimoles per Liter (mmol/L) | Standard Error 0.2 |
| Premix Insulin Lispro | 7-point Self-monitored Blood Glucose Profiles | Week 48 Before Lunch (n=121, n=129) | 6.86 millimoles per Liter (mmol/L) | Standard Error 0.19 |
| Premix Insulin Lispro | 7-point Self-monitored Blood Glucose Profiles | Week 32 at 0300 Hours (n=105, n=106) | 6.80 millimoles per Liter (mmol/L) | Standard Error 0.31 |
| Premix Insulin Lispro | 7-point Self-monitored Blood Glucose Profiles | Week 16 After Lunch (n=138, n=140) | 9.37 millimoles per Liter (mmol/L) | Standard Error 0.25 |
| Premix Insulin Lispro | 7-point Self-monitored Blood Glucose Profiles | Week 16 After Dinner (n=140, n=141) | 9.03 millimoles per Liter (mmol/L) | Standard Error 0.26 |
Secondary
Body Weight Change From Baseline to Endpoint
Time frame: baseline, 48 weeks
Population: Safety Set Population: All participants who received at least one dose of study drug during the treatment period and had measurement at baseline and endpoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Glargine | Body Weight Change From Baseline to Endpoint | 2.70 kilograms (kg) |
| Premix Insulin Lispro | Body Weight Change From Baseline to Endpoint | 2.61 kilograms (kg) |
95% CI: [-0.89, 0.7]
Secondary
HbA1c Over Time
Least Squares Mean (LSMean) values were adjusted based on a mixed effect linear regression model with a participant specific random effect: HbA1c = Treatment + Country + HbA1c baseline value + Ramadan holiday between Visit 10 (Week 36) and Visit 12 (Week 48) (yes/no) + visit + visit\*treatment in Full Analysis Set (FAS) Population.
Time frame: 16 weeks, 32 weeks, and 48 weeks
Population: Full Analysis Set: All participants who enrolled in this study, completed Screening, were randomized to one of the study treatments, and had at least one post baseline measurement for the dependent variable, according to intent-to-treat (ITT) principles.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Glargine | HbA1c Over Time | 16 weeks (n=142,n=140) | 7.57 percent glycosylated hemoglobin |
| Glargine | HbA1c Over Time | 32 weeks (n=119, n=121) | 7.43 percent glycosylated hemoglobin |
| Glargine | HbA1c Over Time | 48 weeks (n=115,n=125) | 7.40 percent glycosylated hemoglobin |
| Premix Insulin Lispro | HbA1c Over Time | 16 weeks (n=142,n=140) | 7.62 percent glycosylated hemoglobin |
| Premix Insulin Lispro | HbA1c Over Time | 32 weeks (n=119, n=121) | 7.46 percent glycosylated hemoglobin |
| Premix Insulin Lispro | HbA1c Over Time | 48 weeks (n=115,n=125) | 7.33 percent glycosylated hemoglobin |
95% CI: [-0.18, 0.29]
95% CI: [-0.22, 0.29]
95% CI: [-0.33, 0.18]
Secondary
Incidence of All Self-reported Hypoglycemic Episodes
Percentage of participants with self-reported hypoglycemic episodes at any time during the study. A hypoglycemic episode is defined as any time a participant feels that he/she is experiencing a sign or symptom that is associated with hypoglycemia, or has a blood glucose level of ≤70 mg/dL (3.9 mmol/L) (Roche plasma glucose) or ≤75 mg/dL (4.2 mmol/L) (IFCC Plasma Values), even if it was not associated with signs, symptoms, or treatment consistent with current guidelines (ADA 2005).
Time frame: Baseline to 48 weeks
Population: Safety Set Population: All participants who received at least one dose of study drug during the treatment period and had measurement at baseline and endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Glargine | Incidence of All Self-reported Hypoglycemic Episodes | 60.1 percentage of participants |
| Premix Insulin Lispro | Incidence of All Self-reported Hypoglycemic Episodes | 64.5 percentage of participants |
p-value: 0.4935Fisher Exact
Secondary
Mean Daily Total, Basal and Prandial Insulin Dose
Time frame: 16 weeks, 32 weeks and 48 weeks
Population: Full Analysis Set: All participants who enrolled in this study, completed Screening, were randomized to one of the study treatments, and had at least one post baseline measurement for the dependent variable, according to intent-to-treat (ITT) principles.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Glargine | Mean Daily Total, Basal and Prandial Insulin Dose | Week 32 Total Daily Insulin (N=135, N=140) | 40.80 International Units per day (IU/day) | Standard Deviation 27.037 |
| Glargine | Mean Daily Total, Basal and Prandial Insulin Dose | Week 48 Basal Insulin (N=130, N=137) | 31.52 International Units per day (IU/day) | Standard Deviation 17.194 |
| Glargine | Mean Daily Total, Basal and Prandial Insulin Dose | Week 16 Basal Insulin (N=156, N=155) | 25.53 International Units per day (IU/day) | Standard Deviation 13.239 |
| Glargine | Mean Daily Total, Basal and Prandial Insulin Dose | Week 16 Prandial Insulin (N=156, N=155) | 4.41 International Units per day (IU/day) | Standard Deviation 9.181 |
| Glargine | Mean Daily Total, Basal and Prandial Insulin Dose | Week 48 Total Daily Insulin (N=130, N=137) | 46.45 International Units per day (IU/day) | Standard Deviation 31.402 |
| Glargine | Mean Daily Total, Basal and Prandial Insulin Dose | Week 32 Prandial Insulin (N=135, N=140) | 10.75 International Units per day (IU/day) | Standard Deviation 14.901 |
| Glargine | Mean Daily Total, Basal and Prandial Insulin Dose | Week 32 Basal Insulin (N=135, N=140) | 30.05 International Units per day (IU/day) | Standard Deviation 16.211 |
| Glargine | Mean Daily Total, Basal and Prandial Insulin Dose | Week 48 Prandial Insulin (N=130, N=137) | 14.94 International Units per day (IU/day) | Standard Deviation 19.082 |
| Glargine | Mean Daily Total, Basal and Prandial Insulin Dose | Week 16 Total Daily Insulin (N=156, N=155) | 29.94 International Units per day (IU/day) | Standard Deviation 18.523 |
| Premix Insulin Lispro | Mean Daily Total, Basal and Prandial Insulin Dose | Week 48 Prandial Insulin (N=130, N=137) | 16.07 International Units per day (IU/day) | Standard Deviation 10.28 |
| Premix Insulin Lispro | Mean Daily Total, Basal and Prandial Insulin Dose | Week 16 Total Daily Insulin (N=156, N=155) | 26.94 International Units per day (IU/day) | Standard Deviation 15.398 |
| Premix Insulin Lispro | Mean Daily Total, Basal and Prandial Insulin Dose | Week 32 Total Daily Insulin (N=135, N=140) | 38.45 International Units per day (IU/day) | Standard Deviation 23.876 |
| Premix Insulin Lispro | Mean Daily Total, Basal and Prandial Insulin Dose | Week 48 Total Daily Insulin (N=130, N=137) | 46.20 International Units per day (IU/day) | Standard Deviation 28.396 |
| Premix Insulin Lispro | Mean Daily Total, Basal and Prandial Insulin Dose | Week 16 Basal Insulin (N=156, N=155) | 17.97 International Units per day (IU/day) | Standard Deviation 10.636 |
| Premix Insulin Lispro | Mean Daily Total, Basal and Prandial Insulin Dose | Week 32 Basal Insulin (N=135, N=140) | 25.06 International Units per day (IU/day) | Standard Deviation 15.763 |
| Premix Insulin Lispro | Mean Daily Total, Basal and Prandial Insulin Dose | Week 48 Basal Insulin (N=130, N=137) | 30.12 International Units per day (IU/day) | Standard Deviation 18.612 |
| Premix Insulin Lispro | Mean Daily Total, Basal and Prandial Insulin Dose | Week 16 Prandial Insulin (N=156, N=155) | 8.97 International Units per day (IU/day) | Standard Deviation 5.472 |
| Premix Insulin Lispro | Mean Daily Total, Basal and Prandial Insulin Dose | Week 32 Prandial Insulin (N=135, N=140) | 13.39 International Units per day (IU/day) | Standard Deviation 8.599 |
Secondary
Mean Postprandial Blood Glucose Values
Mean postprandial blood glucose values were assessed using GlycoMark, which is an FDA-approved blood test measuring levels of 1,5 anhydroglucitol (1,5 AG) in serum or plasma. When 1,5 AG values decrease, serum glucose levels increase.
Time frame: Baseline, 16 weeks, 32 weeks and 48 weeks
Population: Full Analysis Set: All participants who enrolled in this study, completed Screening, were randomized to one of the study treatments, and had at least one post baseline measurement for the dependent variable, according to intent-to-treat (ITT) principles.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Glargine | Mean Postprandial Blood Glucose Values | Baseline (N=160, N=158) | 6.25 microgram per milliliter (µg/mL) | Standard Deviation 5.804 |
| Glargine | Mean Postprandial Blood Glucose Values | Week 16 (N=143, N=141) | 9.69 microgram per milliliter (µg/mL) | Standard Deviation 6.161 |
| Glargine | Mean Postprandial Blood Glucose Values | Week 48 (N=119, N=125) | 10.90 microgram per milliliter (µg/mL) | Standard Deviation 6.661 |
| Glargine | Mean Postprandial Blood Glucose Values | Week 32 (N=125, N=123) | 10.54 microgram per milliliter (µg/mL) | Standard Deviation 7.098 |
| Premix Insulin Lispro | Mean Postprandial Blood Glucose Values | Week 48 (N=119, N=125) | 11.41 microgram per milliliter (µg/mL) | Standard Deviation 7.344 |
| Premix Insulin Lispro | Mean Postprandial Blood Glucose Values | Baseline (N=160, N=158) | 5.69 microgram per milliliter (µg/mL) | Standard Deviation 4.426 |
| Premix Insulin Lispro | Mean Postprandial Blood Glucose Values | Week 16 (N=143, N=141) | 9.52 microgram per milliliter (µg/mL) | Standard Deviation 5.767 |
| Premix Insulin Lispro | Mean Postprandial Blood Glucose Values | Week 32 (N=125, N=123) | 10.81 microgram per milliliter (µg/mL) | Standard Deviation 6.824 |
p-value: 0.6615Wilcoxon (Mann-Whitney)
p-value: 0.9798Wilcoxon (Mann-Whitney)
p-value: 0.6169Wilcoxon (Mann-Whitney)
p-value: 0.7834Wilcoxon (Mann-Whitney)
Secondary
Number of Participants With Adverse Events
A summary of serious adverse events (SAEs) and all other non-serious treatment-emergent adverse events (TEAE) is located in the Reported Adverse Event Module. TEAEs are defined as events that are newly reported after randomization or reported to worsen in severity from baseline.
Time frame: Baseline to 48 weeks
Population: Safety Set Population: All participants who received at least one dose of study drug during the treatment period.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Glargine | Number of Participants With Adverse Events | SAE | 3 participants |
| Glargine | Number of Participants With Adverse Events | TEAE | 53 participants |
| Premix Insulin Lispro | Number of Participants With Adverse Events | SAE | 7 participants |
| Premix Insulin Lispro | Number of Participants With Adverse Events | TEAE | 52 participants |
Secondary
Percentage of Participants Using Each Possible Final Insulin Regimen
Insulin Regimens: Lispro: Mid-Mix (MM) before noon; Low-Mix (LM) before evening (PM); MM before noon+LM before PM; LM before morning (AM)+MM before noon + LM before PM; MM before AM +MM before noon+LM before PM Glargine: Glargine once a day (QD); Glargine QD + 1 Lispro (noon or PM); Glargine QD + 2 Lispro (noon and PM); Glargine QD + 3 Lispro.
Time frame: 48 weeks
Population: Full Analysis Set: All participants who enrolled in this study, completed Screening, were randomized to one of the study treatments, and had a measurement for the dependent variable at the time point, according to intent-to-treat (ITT) principles.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Glargine | Percentage of Participants Using Each Possible Final Insulin Regimen | MM before noon | 0 percentage of participants |
| Glargine | Percentage of Participants Using Each Possible Final Insulin Regimen | LM before PM | 0 percentage of participants |
| Glargine | Percentage of Participants Using Each Possible Final Insulin Regimen | MM before noon+LM before PM | 0 percentage of participants |
| Glargine | Percentage of Participants Using Each Possible Final Insulin Regimen | LM before AM+MM before noon+LM before PM | 0 percentage of participants |
| Glargine | Percentage of Participants Using Each Possible Final Insulin Regimen | MM before AM+MM before noon+LM before PM | 0 percentage of participants |
| Glargine | Percentage of Participants Using Each Possible Final Insulin Regimen | Glargine QD | 59 percentage of participants |
| Glargine | Percentage of Participants Using Each Possible Final Insulin Regimen | Glargine QD+1 Lispro (noon or PM) | 27 percentage of participants |
| Glargine | Percentage of Participants Using Each Possible Final Insulin Regimen | Glargine QD+2 Lispro (noon and PM) | 30 percentage of participants |
| Glargine | Percentage of Participants Using Each Possible Final Insulin Regimen | Glargine QD+3 Lispro | 14 percentage of participants |
| Glargine | Percentage of Participants Using Each Possible Final Insulin Regimen | Other (not specified) | 0 percentage of participants |
| Premix Insulin Lispro | Percentage of Participants Using Each Possible Final Insulin Regimen | Glargine QD+2 Lispro (noon and PM) | 0 percentage of participants |
| Premix Insulin Lispro | Percentage of Participants Using Each Possible Final Insulin Regimen | MM before noon | 15 percentage of participants |
| Premix Insulin Lispro | Percentage of Participants Using Each Possible Final Insulin Regimen | Glargine QD | 0 percentage of participants |
| Premix Insulin Lispro | Percentage of Participants Using Each Possible Final Insulin Regimen | LM before PM | 33 percentage of participants |
| Premix Insulin Lispro | Percentage of Participants Using Each Possible Final Insulin Regimen | Other (not specified) | 4 percentage of participants |
| Premix Insulin Lispro | Percentage of Participants Using Each Possible Final Insulin Regimen | MM before noon+LM before PM | 42 percentage of participants |
| Premix Insulin Lispro | Percentage of Participants Using Each Possible Final Insulin Regimen | Glargine QD+1 Lispro (noon or PM) | 0 percentage of participants |
| Premix Insulin Lispro | Percentage of Participants Using Each Possible Final Insulin Regimen | LM before AM+MM before noon+LM before PM | 36 percentage of participants |
| Premix Insulin Lispro | Percentage of Participants Using Each Possible Final Insulin Regimen | Glargine QD+3 Lispro | 0 percentage of participants |
| Premix Insulin Lispro | Percentage of Participants Using Each Possible Final Insulin Regimen | MM before AM+MM before noon+LM before PM | 7 percentage of participants |
Secondary
Percentage of Patients Achieving HbA1c Less Than or Equal to 6.5% and Less Than or Equal to 7% Over Time
Time frame: 16 weeks, 32 weeks and 48 weeks
Population: Full Analysis Set: All participants who enrolled in this study, completed Screening, were randomized to one of the study treatments, and had at least one post baseline measurement for the dependent variable, according to intent-to-treat (ITT) principles.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Glargine | Percentage of Patients Achieving HbA1c Less Than or Equal to 6.5% and Less Than or Equal to 7% Over Time | Week 16 HbA1c <=7.0% (n=157, n=155) | 24.2 percentage of participants |
| Glargine | Percentage of Patients Achieving HbA1c Less Than or Equal to 6.5% and Less Than or Equal to 7% Over Time | Week 16 HbA1c <=6.5% (n=157, n=155) | 14.6 percentage of participants |
| Glargine | Percentage of Patients Achieving HbA1c Less Than or Equal to 6.5% and Less Than or Equal to 7% Over Time | Week 32 HbA1c <=7.0% (n=137, n=141) | 32.1 percentage of participants |
| Glargine | Percentage of Patients Achieving HbA1c Less Than or Equal to 6.5% and Less Than or Equal to 7% Over Time | Week 32 HbA1c <=6.5% (n=137, n=141) | 19.0 percentage of participants |
| Glargine | Percentage of Patients Achieving HbA1c Less Than or Equal to 6.5% and Less Than or Equal to 7% Over Time | Week 48 HbA1c <=7.0% (n=130, n=137) | 36.2 percentage of participants |
| Glargine | Percentage of Patients Achieving HbA1c Less Than or Equal to 6.5% and Less Than or Equal to 7% Over Time | Week 48 HbA1c <=6.5% (n=130, n=137) | 18.5 percentage of participants |
| Premix Insulin Lispro | Percentage of Patients Achieving HbA1c Less Than or Equal to 6.5% and Less Than or Equal to 7% Over Time | Week 48 HbA1c <=7.0% (n=130, n=137) | 48.2 percentage of participants |
| Premix Insulin Lispro | Percentage of Patients Achieving HbA1c Less Than or Equal to 6.5% and Less Than or Equal to 7% Over Time | Week 16 HbA1c <=7.0% (n=157, n=155) | 30.3 percentage of participants |
| Premix Insulin Lispro | Percentage of Patients Achieving HbA1c Less Than or Equal to 6.5% and Less Than or Equal to 7% Over Time | Week 32 HbA1c <=6.5% (n=137, n=141) | 20.6 percentage of participants |
| Premix Insulin Lispro | Percentage of Patients Achieving HbA1c Less Than or Equal to 6.5% and Less Than or Equal to 7% Over Time | Week 16 HbA1c <=6.5% (n=157, n=155) | 18.7 percentage of participants |
| Premix Insulin Lispro | Percentage of Patients Achieving HbA1c Less Than or Equal to 6.5% and Less Than or Equal to 7% Over Time | Week 48 HbA1c <=6.5% (n=130, n=137) | 24.8 percentage of participants |
| Premix Insulin Lispro | Percentage of Patients Achieving HbA1c Less Than or Equal to 6.5% and Less Than or Equal to 7% Over Time | Week 32 HbA1c <=7.0% (n=137, n=141) | 37.6 percentage of participants |
p-value: 0.2524Chi-squared
p-value: 0.2127Chi-squared
p-value: 0.3281Chi-squared
p-value: 0.2812Chi-squared
p-value: 0.6963Chi-squared
p-value: 0.0643Chi-squared
Secondary
Rate Per 30 Days of All Self-reported Hypoglycemic Episodes
The hypoglycemia rate between two visits will be calculated as the total number of episodes between the two visits divided by the number of days between the visits, and then multiplied by 30 days (rate per patient per 30 days).
Time frame: Baseline to 48 weeks
Population: Safety Set Population: All participants who received at least one dose of study drug during the treatment period and had measurement at baseline and endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glargine | Rate Per 30 Days of All Self-reported Hypoglycemic Episodes | 0.67 episodes per 30 days | Standard Deviation 1.106 |
| Premix Insulin Lispro | Rate Per 30 Days of All Self-reported Hypoglycemic Episodes | 0.79 episodes per 30 days | Standard Deviation 1.587 |