Diabetes Mellitus, Type 2
Conditions
Keywords
Type 2 Diabetes, Insulin, Algorithms, Blood glucose levels
Brief summary
Evidence regarding optimal methods of insulin dose adjustment is lacking in the literature. The purpose of this study is to evaluate the efficacy and safety of two approaches to escalate prandial insulin therapy in participants with type 2 diabetes mellitus not achieving adequate glycemic control on basal insulin.
Detailed description
Participants who enter the study and are already taking insulin glargine with a screening HbA1c \>7.0% will be randomized to one of two treatment arms. Both arms will add prandial insulin to existing basal insulin therapy.
Interventions
DRUGInsulin lispro
Administered subcutaneously, up to three times daily for 24 weeks
DRUGGlargine
Administered subcutaneously, dosage determined by investigator once daily for 24 weeks
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Have type 2 diabetes * Have been treated for at least 90 days with insulin glargine, neutral protamine Hagedorn (NPH), or detemir in combination with oral antihyperglycemic agents as monotherapy, dual, or triple therapy \[sulfonylurea, meglitinide, metformin, pioglitazone, or dipeptidyl peptidase-4 (DPP-4) inhibitor\] and in the opinion of the investigator requires further intensification of therapy * Are treated with insulin glargine, NPH, or detemir at least 20 units per day (U/day) at enrollment * Have an glycated hemoglobin (HbA1c) value greater than 7.0% and less than or equal to 12.0% according to the central laboratory at screening * Capable of and willing to do the following: inject insulin with a prefilled pen, perform self blood glucose monitoring and record keeping as required by this protocol, as determined by the investigator * Have given written informed consent to participate in this study in accordance with local regulations
Exclusion criteria
* Prior rapid- or short-acting insulin therapy: participants receiving scheduled long-term short-acting or rapid-acting or premixed insulin therapy within the past 6 months will not be eligible to participate in the study. Participants who have previously received short- or rapid-acting insulin as part of short-term insulin therapy (during gestational diabetes, during an acute hospitalization or illness) or occasional use will be allowed to participate in this study. Occasional use (e.g., used to treat acute hyperglycemia) shall be defined as less than daily administration of not more than 1 dose per day of short- or rapid-acting insulin * Concomitant medications: glucagon-like peptide-1 (GLP-1) receptor agonist, alpha-glucosidase inhibitor, or rosiglitazone use concurrently or within 3 months prior to entry into the study * Severe hypoglycemia: have had more than one episode of severe hypoglycemia (defined as requiring assistance of a third party due to disabling hypoglycemia) within 6 months prior to entry into the study * Excessive insulin resistance: received a total daily dose of insulin greater than 2.0 units per kilogram (U/kg) at the time of randomization * Morbid obesity: defined as a body mass index greater than or equal to 45 kilograms per square meter (kg/m²) * Malignancy: have active or untreated malignancy, or have been in remission from clinically significant malignancy (other than basal cell or squamous cell skin cancer) for less than 5 years * Cardiovascular: have cardiac disease with functional status that is New York Heart Association Class III or IV (see New York Heart Association Cardiac Disease Classifications) or have Congestive Heart Failure (CHF) requiring pharmacologic treatment or, in the investigator's opinion, have severe dependent edema (i.e., edema of the feet or ankles) or have any condition associated with hypoperfusion, hypoxemia, dehydration, or sepsis * Renal: have a history of renal transplantation or are currently receiving renal dialysis or have serum creatinine greater than or equal to 2 milligrams per deciliter (mg/dL) if not on metformin * Hepatic: have obvious clinical signs or symptoms of liver disease, acute or chronic hepatitis, or alanine aminotransferase/serum glutamic pyruvic transaminase (ALT/SGPT) greater than 3 times the upper limit of the reference range as defined by the central laboratory * Hematologic: have known hemoglobinopathy or chronic anemia or other known blood disorder * Reproductive:(for women) are pregnant or intend to become pregnant during the course of the study; are sexually active women of childbearing potential not actively practicing birth control by a method determined by the investigator to be medically acceptable; or are breastfeeding * Allergy: have known allergy to insulin lispro, insulin glargine, or excipients contained in these products * Glucocorticoid therapy: receiving chronic (lasting longer than 2 weeks) systemic glucocorticoid therapy (excluding topical and inhaled preparations) or have received such therapy within 2 weeks immediately before screening * Adherence to protocol: have any other condition (including known drug or alcohol abuse or psychiatric disorder) that precludes the participant from following and completing the protocol * Prior participation: are currently enrolled in, or have participated in, an interventional medical, surgical, or pharmaceutical drug or device or off-label use study (an investigational study in which a medical or surgical treatment was given) within 30 days prior to entry into the study, or persons who have previously completed or withdrawn from this study (after having signed the informed consent document). Participants may be ineligible if they are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study * Non-approved drug: have been treated with a drug within the last 30 days that has not received regulatory approval at the time of study entry
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to 24 Week Endpoint in Glycated Hemoglobin (HbA1c) | Baseline, 24 weeks | The change from baseline to 24 weeks in the percentage of HbA1c in plasma. The Least Squares (LS) mean was estimated from a mixed-effects model with repeated measures (MMRM) that included the independent variables: fixed effects for treatment, country, sulfonylurea/meglitinide use, visit, treatment by visit interaction with baseline HbA1c as a covariate. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants ≥65 Years of Age Achieving Glycated Hemoglobin (HbA1c) Target Concentration | 24-week endpoint | Percentage of participants ≥65 years of age achieving HbA1c target concentration of ≤7.0% or ≤6.5%. |
| Change From Baseline to 24 Week Endpoint in Body Weight | Baseline, 24-weeks | Body weight was measured twice at each indicated visit and the average of the 2 measurements was used for analyses. Least Squares (LS) mean calculated using mixed model repeating measure (MMRM) analysis that included baseline, treatment, country, sulfonylurea/meglitinide use, baseline glycated hemoglobin (HbA1c) strata (≤8% and \>8%), visit and treatment-by-visit interaction . |
| Time to Reach Glycated Hemoglobin (HbA1c) Target Values | Baseline through 24 weeks | Percentage of participants is the number of participants who achieved HbA1c target values of ≤6.5% or ≤7.0% during the specified time period divided by the total number of participants who did not discontinue from the study but had not reached HbA1c target at the beginning of the specified post baseline time period (≤100 days and ≥101 days). Participants who did not experience an outcome before discontinuation or completion of the study were censored using the date of discontinuation. Participants who were lost to follow up the date of discontinuation were considered to be the date of last contact. |
| Change From Baseline to 24 Week Endpoint in Fasting Glucose | Baseline, 24 weeks | Least Squares (LS) mean calculated using mixed model repeating measure (MMRM) analysis that included baseline, treatment, country, sulfonylurea/meglitinide use, baseline glycated hemoglobin (HbA1c) strata (≤8% and \>8%), visit and treatment-by-visit interaction. |
| Change From Baseline to 24 Week Endpoint in Fasting Glucose in Participants ≥65 Years of Age | Baseline, 24 weeks | Least Squares (LS) mean calculated using mixed model repeating measure (MMRM) analysis that included baseline, treatment, country, sulfonylurea/meglitinide use, baseline glycated hemoglobin (HbA1c) strata (≤8% and \>8%), visit and treatment-by-visit interaction. |
| Change From Baseline to 24 Week Endpoint in 1,5-anhydroglucitol (1,5-AG) | Baseline, 24 weeks | Least Squares (LS) mean calculated using mixed model repeating measure (MMRM) analysis that included baseline treatment, country, sulfonylurea/meglitinide use, baseline glycated hemoglobin (HbA1c) strata (≤8% and \>8%), visit and treatment-by-visit interaction. |
| Percentage of Participants Achieving Glycated Hemoglobin (HbA1c) Target Values | 24-week endpoint | Percentage of participants who achieved HbA1c levels of ≤7.0% or ≤6.5%. |
| Daily Dose of Insulin: Total, Basal and Prandial (Bolus) | 24 weeks | Total insulin was the sum of basal insulin (glargine) that was required to manage normal daily blood fluctuations and prandial insulin that was taken at meal time. Least Squares (LS) mean calculated using mixed model repeating measure (MMRM) analysis that included baseline, treatment, country, sulfonylurea/meglitinide use, baseline glycated hemoglobin (HbA1c) strata (≤8% and \>8%), visit and treatment-by-visit interaction. |
| Daily Dose of Insulin Per Kilogram of Body Weight: Total, Basal and Prandial (Bolus) | 24 weeks | Total insulin was the sum of basal insulin (glargine) that was required to manage normal daily blood fluctuations and prandial insulin that was taken at meal time. Total, basal and prandial amounts were then divided by the participant's body weight in kilograms (kg). Least Squares (LS) mean calculated using mixed model repeating measure (MMRM) analysis that included baseline, treatment, country, sulfonylurea/meglitinide use, baseline glycated hemoglobin (HbA1c) strata (≤8% and \>8%), visit and treatment-by-visit interaction. |
| The Number of Participants With a Hypoglycemic Episode (Incidence) | Randomization through 24 weeks overall | A hypoglycemic episode was defined as any time a participant felt they were experiencing a sign or symptom that was associated with hypoglycemia, or had a blood glucose level of ≤70 milligram per deciliter \[mg/dL, ≤3.9 millimoles per liter (mmol/L)\] even if it was not associated with signs, symptoms or treatment (consistent with current American Diabetes Association 2005 guidelines). |
| The Number of Participants ≥65 Years of Age With Hypoglycemic Episodes (Incidence) | Randomization through 24 weeks overall | A hypoglycemic episode in participants ≥ 65 years of age was defined as any time a participant felt they were experiencing a sign or symptom that was associated with hypoglycemia, or had a blood glucose level of ≤70 milligram per deciliter \[mg/dL, ≤3.9 millimoles per liter (mmol/L)\] even if it was not associated with signs, symptoms or treatment (consistent with current American Diabetes Association 2005 guidelines). |
| The Rate of Hypoglycemic Episodes | Randomization through 24 weeks overall | The hypoglycemia rate per 30 days was calculated as the number of hypoglycemic episodes reported divided by the number of days at risk times 30. |
| Percentage of Participants With Severe Hypoglycemic Episodes | Randomization up to 24 weeks | Severe hypoglycemia is defined as an event requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. These episodes may be associated with sufficient neuroglycopenia to induce seizure or coma. Plasma glucose measurements may not be available during such an event, but neurological recovery attributable to the restoration of plasma glucose to normal is considered sufficient evidence that the event was induced by low plasma glucose. |
| Change From Baseline to 24 Weeks in 7-Point Self-Monitored Blood Glucose (SMBG) Profile | Baseline, 24 weeks | 7-Point Self-Monitored Blood Glucose profiles are measures of blood glucose concentration taken 7 time a day at the morning pre-meal, morning 2-hours (HR) postprandial (PP), midday pre-meal, midday 2-hours post-meal, evening pre-meal, bedtime and 0300 hour (3 am). Each participant took measures over any 3 days and the average was calculated for each of the 7 time points. Least Squares (LS) mean calculated using mixed model repeating measure (MMRM) analysis that included baseline, treatment, country, sulfonylurea/meglitinide use, baseline glycated hemoglobin (HbA1c) strata (≤8% and \>8%), visit and treatment-by-visit interaction. |
Countries
Argentina, Austria, Brazil, Canada, Croatia, Denmark, France, Lithuania, Mexico, Poland, Puerto Rico, Romania, Russia, South Africa, United States
Participant flow
Pre-assignment details
Protocol had 2 independent studies (Study A, Study B) from which data was analyzed separately and independently: Participants were randomized to 1of the 2 treatment arms (Q1D, Q3D) at the site level. Sites were assigned to a study according to an allocation plan that was pre-specified before initiation of the study.
Participants by arm
| Arm | Count |
|---|---|
| Study A Q1D Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose reading from the previous day (Q1D).
Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks.
Participants were randomized to Q1D at the site level: sites were assigned to Study A according to an allocation plan that was pre-specified before initiation of Study A. | 267 |
| Study A Q3D Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated based dose was on blood glucose readings from the past 3 days (Q3D).
Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks.
Participants were randomized to Q3D at the site level: sites were assigned to Study A according to an allocation plan that was pre-specified before initiation of Study A. | 261 |
| Study B Q1D Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose reading from the previous day (Q1D).
Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks.
Participants were randomized to Q1D at the site level: sites were assigned to Study B according to an allocation plan that was pre-specified before initiation of Study B. | 288 |
| Study B Q3D Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose readings from the past 3 days (Q3D).
Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks.
Participants were randomized to Q3D at the site level: sites were assigned to Study B according to an allocation plan that was pre-specified before initiation of Study B. | 290 |
| Total | 1,106 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 4 | 2 | 3 |
| Overall Study | Death | 2 | 0 | 1 | 3 |
| Overall Study | Entry Criteria Not Met | 1 | 3 | 4 | 7 |
| Overall Study | Lack of Efficacy | 1 | 2 | 1 | 0 |
| Overall Study | Lost to Follow-up | 4 | 4 | 8 | 9 |
| Overall Study | Physician Decision | 4 | 10 | 8 | 11 |
| Overall Study | Protocol Violation | 17 | 13 | 8 | 8 |
| Overall Study | Quality Issues | 0 | 0 | 3 | 2 |
| Overall Study | Sponsor Decision | 1 | 2 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 14 | 15 | 13 | 9 |
Baseline characteristics
| Characteristic | Study A Q1D | Study A Q3D | Study B Q1D | Study B Q3D | Total |
|---|---|---|---|---|---|
| Age, Continuous | 57.89 years STANDARD_DEVIATION 10.25 | 58.82 years STANDARD_DEVIATION 9.46 | 57.71 years STANDARD_DEVIATION 9.71 | 57.01 years STANDARD_DEVIATION 10.61 | 57.83 years STANDARD_DEVIATION 10.03 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 100 Participants | 96 Participants | 91 Participants | 95 Participants | 382 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 150 Participants | 153 Participants | 182 Participants | 177 Participants | 662 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 17 Participants | 12 Participants | 15 Participants | 18 Participants | 62 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 22 Participants | 20 Participants | 11 Participants | 11 Participants | 64 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 4 Participants | 8 Participants | 2 Participants | 18 Participants |
| Race (NIH/OMB) Black or African American | 20 Participants | 15 Participants | 35 Participants | 29 Participants | 99 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 2 Participants | 4 Participants | 6 Participants | 13 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 2 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) White | 219 Participants | 218 Participants | 228 Participants | 240 Participants | 905 Participants |
| Region of Enrollment Argentina | 28 participants | 28 participants | 37 participants | 38 participants | 131 participants |
| Region of Enrollment Austria | 0 participants | 1 participants | 4 participants | 1 participants | 6 participants |
| Region of Enrollment Brazil | 2 participants | 4 participants | 11 participants | 14 participants | 31 participants |
| Region of Enrollment Canada | 5 participants | 6 participants | 7 participants | 11 participants | 29 participants |
| Region of Enrollment Croatia | 3 participants | 3 participants | 4 participants | 5 participants | 15 participants |
| Region of Enrollment Denmark | 5 participants | 0 participants | 1 participants | 0 participants | 6 participants |
| Region of Enrollment France | 3 participants | 0 participants | 1 participants | 3 participants | 7 participants |
| Region of Enrollment Lithuania | 2 participants | 4 participants | 4 participants | 5 participants | 15 participants |
| Region of Enrollment Mexico | 31 participants | 31 participants | 21 participants | 25 participants | 108 participants |
| Region of Enrollment Poland | 9 participants | 8 participants | 15 participants | 15 participants | 47 participants |
| Region of Enrollment Puerto Rico | 26 participants | 19 participants | 7 participants | 7 participants | 59 participants |
| Region of Enrollment Romania | 9 participants | 6 participants | 11 participants | 10 participants | 36 participants |
| Region of Enrollment Russian Federation | 12 participants | 13 participants | 15 participants | 16 participants | 56 participants |
| Region of Enrollment South Africa | 1 participants | 2 participants | 11 participants | 13 participants | 27 participants |
| Region of Enrollment United States | 131 participants | 136 participants | 139 participants | 127 participants | 533 participants |
| Sex: Female, Male Female | 133 Participants | 138 Participants | 155 Participants | 155 Participants | 581 Participants |
| Sex: Female, Male Male | 134 Participants | 123 Participants | 133 Participants | 135 Participants | 525 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 136 / 268 | 142 / 263 | 130 / 289 | 150 / 292 |
| serious Total, serious adverse events | 21 / 268 | 17 / 263 | 21 / 289 | 27 / 292 |
Outcome results
Primary
Change From Baseline to 24 Week Endpoint in Glycated Hemoglobin (HbA1c)
The change from baseline to 24 weeks in the percentage of HbA1c in plasma. The Least Squares (LS) mean was estimated from a mixed-effects model with repeated measures (MMRM) that included the independent variables: fixed effects for treatment, country, sulfonylurea/meglitinide use, visit, treatment by visit interaction with baseline HbA1c as a covariate.
Time frame: Baseline, 24 weeks
Population: Full Analysis Set: All participants who completed the lead-in period (if applicable), were randomized, received ≥1 dose of study insulin with a baseline value for HbA1C, except participants from the excluded site.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Study A Q1D | Change From Baseline to 24 Week Endpoint in Glycated Hemoglobin (HbA1c) | -1.00 percentage HbA1c | Standard Error 0.08 |
| Study A Q3D | Change From Baseline to 24 Week Endpoint in Glycated Hemoglobin (HbA1c) | -0.96 percentage HbA1c | Standard Error 0.08 |
| Study B Q1D | Change From Baseline to 24 Week Endpoint in Glycated Hemoglobin (HbA1c) | -0.98 percentage HbA1c | Standard Error 0.07 |
| Study B Q3D | Change From Baseline to 24 Week Endpoint in Glycated Hemoglobin (HbA1c) | -0.92 percentage HbA1c | Standard Error 0.07 |
95% CI: [-0.15, 0.22]
95% CI: [-0.12, 0.24]
Secondary
Change From Baseline to 24 Week Endpoint in 1,5-anhydroglucitol (1,5-AG)
Least Squares (LS) mean calculated using mixed model repeating measure (MMRM) analysis that included baseline treatment, country, sulfonylurea/meglitinide use, baseline glycated hemoglobin (HbA1c) strata (≤8% and \>8%), visit and treatment-by-visit interaction.
Time frame: Baseline, 24 weeks
Population: Full Analysis Set: all participants who completed the lead-in period (if applicable), were randomized, received ≥1 dose of study insulin with baseline 1,5-AG value, except participants from the excluded site.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Study A Q1D | Change From Baseline to 24 Week Endpoint in 1,5-anhydroglucitol (1,5-AG) | 3.24 microgram/milliliter (mcg/mL) | Standard Error 0.35 |
| Study A Q3D | Change From Baseline to 24 Week Endpoint in 1,5-anhydroglucitol (1,5-AG) | 3.09 microgram/milliliter (mcg/mL) | Standard Error 0.36 |
| Study B Q1D | Change From Baseline to 24 Week Endpoint in 1,5-anhydroglucitol (1,5-AG) | 3.22 microgram/milliliter (mcg/mL) | Standard Error 0.32 |
| Study B Q3D | Change From Baseline to 24 Week Endpoint in 1,5-anhydroglucitol (1,5-AG) | 2.95 microgram/milliliter (mcg/mL) | Standard Error 0.31 |
p-value: 0.72395% CI: [-0.95, 0.66]Mixed Models Analysis
p-value: 0.49595% CI: [-1.08, 0.52]Mixed Models Analysis
Secondary
Change From Baseline to 24 Week Endpoint in Body Weight
Body weight was measured twice at each indicated visit and the average of the 2 measurements was used for analyses. Least Squares (LS) mean calculated using mixed model repeating measure (MMRM) analysis that included baseline, treatment, country, sulfonylurea/meglitinide use, baseline glycated hemoglobin (HbA1c) strata (≤8% and \>8%), visit and treatment-by-visit interaction .
Time frame: Baseline, 24-weeks
Population: Full Analysis Set: all participants who completed the lead-in period (if applicable), were randomized and received ≥1 dose of study insulin with a baseline body weight, except participants from the excluded site.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Study A Q1D | Change From Baseline to 24 Week Endpoint in Body Weight | 2.15 kilograms (kg) | Standard Error 0.27 |
| Study A Q3D | Change From Baseline to 24 Week Endpoint in Body Weight | 2.96 kilograms (kg) | Standard Error 0.28 |
| Study B Q1D | Change From Baseline to 24 Week Endpoint in Body Weight | 2.47 kilograms (kg) | Standard Error 0.24 |
| Study B Q3D | Change From Baseline to 24 Week Endpoint in Body Weight | 1.97 kilograms (kg) | Standard Error 0.24 |
p-value: 0.01495% CI: [0.17, 1.46]Mixed Models Analysis
p-value: 0.10895% CI: [-1.12, 0.11]Mixed Models Analysis
Secondary
Change From Baseline to 24 Week Endpoint in Fasting Glucose
Least Squares (LS) mean calculated using mixed model repeating measure (MMRM) analysis that included baseline, treatment, country, sulfonylurea/meglitinide use, baseline glycated hemoglobin (HbA1c) strata (≤8% and \>8%), visit and treatment-by-visit interaction.
Time frame: Baseline, 24 weeks
Population: Full Analysis Set: all participants who completed the lead-in period (if applicable), were randomized, received ≥1 dose of study insulin with baseline fasting glucose values, except participants from the excluded site.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Study A Q1D | Change From Baseline to 24 Week Endpoint in Fasting Glucose | 0.08 millimoles/liter (mmoles/L) | Standard Error 0.22 |
| Study A Q3D | Change From Baseline to 24 Week Endpoint in Fasting Glucose | 0.37 millimoles/liter (mmoles/L) | Standard Error 0.23 |
| Study B Q1D | Change From Baseline to 24 Week Endpoint in Fasting Glucose | -0.36 millimoles/liter (mmoles/L) | Standard Error 0.21 |
| Study B Q3D | Change From Baseline to 24 Week Endpoint in Fasting Glucose | 0.45 millimoles/liter (mmoles/L) | Standard Error 0.21 |
95% CI: [-0.19, 0.77]
95% CI: [0.3, 1.31]
Secondary
Change From Baseline to 24 Week Endpoint in Fasting Glucose in Participants ≥65 Years of Age
Least Squares (LS) mean calculated using mixed model repeating measure (MMRM) analysis that included baseline, treatment, country, sulfonylurea/meglitinide use, baseline glycated hemoglobin (HbA1c) strata (≤8% and \>8%), visit and treatment-by-visit interaction.
Time frame: Baseline, 24 weeks
Population: A subset of the Full Analysis Set: all participants who completed the lead-in period (if applicable), were randomized, received ≥1 dose of study insulin, who are ≥65 years of age with baseline fasting glucose values, except participants from the excluded site.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Study A Q1D | Change From Baseline to 24 Week Endpoint in Fasting Glucose in Participants ≥65 Years of Age | 0.42 millimoles/liter (mmoles/L) | Standard Error 0.44 |
| Study A Q3D | Change From Baseline to 24 Week Endpoint in Fasting Glucose in Participants ≥65 Years of Age | 1.01 millimoles/liter (mmoles/L) | Standard Error 0.46 |
| Study B Q1D | Change From Baseline to 24 Week Endpoint in Fasting Glucose in Participants ≥65 Years of Age | -0.18 millimoles/liter (mmoles/L) | Standard Error 0.5 |
| Study B Q3D | Change From Baseline to 24 Week Endpoint in Fasting Glucose in Participants ≥65 Years of Age | 0.96 millimoles/liter (mmoles/L) | Standard Error 0.46 |
p-value: 0.24295% CI: [-0.4, 1.58]Mixed Models Analysis
p-value: 0.08295% CI: [-0.15, 2.41]Mixed Models Analysis
Secondary
Change From Baseline to 24 Weeks in 7-Point Self-Monitored Blood Glucose (SMBG) Profile
7-Point Self-Monitored Blood Glucose profiles are measures of blood glucose concentration taken 7 time a day at the morning pre-meal, morning 2-hours (HR) postprandial (PP), midday pre-meal, midday 2-hours post-meal, evening pre-meal, bedtime and 0300 hour (3 am). Each participant took measures over any 3 days and the average was calculated for each of the 7 time points. Least Squares (LS) mean calculated using mixed model repeating measure (MMRM) analysis that included baseline, treatment, country, sulfonylurea/meglitinide use, baseline glycated hemoglobin (HbA1c) strata (≤8% and \>8%), visit and treatment-by-visit interaction.
Time frame: Baseline, 24 weeks
Population: Full Analysis Set: all participants who completed the lead-in period (if applicable), were randomized, received ≥1 dose of study insulin and had values at baseline and the specified timepoint, except participants from the excluded site.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Study A Q1D | Change From Baseline to 24 Weeks in 7-Point Self-Monitored Blood Glucose (SMBG) Profile | Evening Pre-Meal (214, 200, 214, 215) | -46.75 milligrams/deciliter (mg/dL) | Standard Error 3.6 |
| Study A Q1D | Change From Baseline to 24 Weeks in 7-Point Self-Monitored Blood Glucose (SMBG) Profile | Midday 2-HR PP (207, 195, 201, 203) | -45.75 milligrams/deciliter (mg/dL) | Standard Error 3.95 |
| Study A Q1D | Change From Baseline to 24 Weeks in 7-Point Self-Monitored Blood Glucose (SMBG) Profile | Midday Pre-Meal (214, 199, 213, 219) | -42.37 milligrams/deciliter (mg/dL) | Standard Error 3.07 |
| Study A Q1D | Change From Baseline to 24 Weeks in 7-Point Self-Monitored Blood Glucose (SMBG) Profile | 0300 hour (3 am) (203, 192, 194, 193) | -26.33 milligrams/deciliter (mg/dL) | Standard Error 3.87 |
| Study A Q1D | Change From Baseline to 24 Weeks in 7-Point Self-Monitored Blood Glucose (SMBG) Profile | Bedtime (214, 200, 214, 216) | -60.61 milligrams/deciliter (mg/dL) | Standard Error 4.78 |
| Study A Q1D | Change From Baseline to 24 Weeks in 7-Point Self-Monitored Blood Glucose (SMBG) Profile | Morning 2-HR PP (208, 194, 202, 201) | -41.57 milligrams/deciliter (mg/dL) | Standard Error 3.74 |
| Study A Q1D | Change From Baseline to 24 Weeks in 7-Point Self-Monitored Blood Glucose (SMBG) Profile | Morning Pre-Meal (215, 200, 214, 219) | -3.97 milligrams/deciliter (mg/dL) | Standard Error 3.02 |
| Study A Q3D | Change From Baseline to 24 Weeks in 7-Point Self-Monitored Blood Glucose (SMBG) Profile | 0300 hour (3 am) (203, 192, 194, 193) | -23.96 milligrams/deciliter (mg/dL) | Standard Error 3.98 |
| Study A Q3D | Change From Baseline to 24 Weeks in 7-Point Self-Monitored Blood Glucose (SMBG) Profile | Morning Pre-Meal (215, 200, 214, 219) | -0.65 milligrams/deciliter (mg/dL) | Standard Error 3.12 |
| Study A Q3D | Change From Baseline to 24 Weeks in 7-Point Self-Monitored Blood Glucose (SMBG) Profile | Morning 2-HR PP (208, 194, 202, 201) | -42.28 milligrams/deciliter (mg/dL) | Standard Error 3.86 |
| Study A Q3D | Change From Baseline to 24 Weeks in 7-Point Self-Monitored Blood Glucose (SMBG) Profile | Midday Pre-Meal (214, 199, 213, 219) | -40.94 milligrams/deciliter (mg/dL) | Standard Error 3.16 |
| Study A Q3D | Change From Baseline to 24 Weeks in 7-Point Self-Monitored Blood Glucose (SMBG) Profile | Midday 2-HR PP (207, 195, 201, 203) | -49.23 milligrams/deciliter (mg/dL) | Standard Error 4.06 |
| Study A Q3D | Change From Baseline to 24 Weeks in 7-Point Self-Monitored Blood Glucose (SMBG) Profile | Evening Pre-Meal (214, 200, 214, 215) | -43.38 milligrams/deciliter (mg/dL) | Standard Error 3.7 |
| Study A Q3D | Change From Baseline to 24 Weeks in 7-Point Self-Monitored Blood Glucose (SMBG) Profile | Bedtime (214, 200, 214, 216) | -62.86 milligrams/deciliter (mg/dL) | Standard Error 4.91 |
| Study B Q1D | Change From Baseline to 24 Weeks in 7-Point Self-Monitored Blood Glucose (SMBG) Profile | Morning 2-HR PP (208, 194, 202, 201) | -43.80 milligrams/deciliter (mg/dL) | Standard Error 2.94 |
| Study B Q1D | Change From Baseline to 24 Weeks in 7-Point Self-Monitored Blood Glucose (SMBG) Profile | 0300 hour (3 am) (203, 192, 194, 193) | -22.40 milligrams/deciliter (mg/dL) | Standard Error 3.75 |
| Study B Q1D | Change From Baseline to 24 Weeks in 7-Point Self-Monitored Blood Glucose (SMBG) Profile | Bedtime (214, 200, 214, 216) | -54.71 milligrams/deciliter (mg/dL) | Standard Error 4.1 |
| Study B Q1D | Change From Baseline to 24 Weeks in 7-Point Self-Monitored Blood Glucose (SMBG) Profile | Evening Pre-Meal (214, 200, 214, 215) | -41.59 milligrams/deciliter (mg/dL) | Standard Error 3.27 |
| Study B Q1D | Change From Baseline to 24 Weeks in 7-Point Self-Monitored Blood Glucose (SMBG) Profile | Midday Pre-Meal (214, 199, 213, 219) | 38.57 milligrams/deciliter (mg/dL) | Standard Error 2.59 |
| Study B Q1D | Change From Baseline to 24 Weeks in 7-Point Self-Monitored Blood Glucose (SMBG) Profile | Midday 2-HR PP (207, 195, 201, 203) | -53.45 milligrams/deciliter (mg/dL) | Standard Error 3.35 |
| Study B Q1D | Change From Baseline to 24 Weeks in 7-Point Self-Monitored Blood Glucose (SMBG) Profile | Morning Pre-Meal (215, 200, 214, 219) | -1.24 milligrams/deciliter (mg/dL) | Standard Error 2.22 |
| Study B Q3D | Change From Baseline to 24 Weeks in 7-Point Self-Monitored Blood Glucose (SMBG) Profile | Morning 2-HR PP (208, 194, 202, 201) | -39.42 milligrams/deciliter (mg/dL) | Standard Error 2.93 |
| Study B Q3D | Change From Baseline to 24 Weeks in 7-Point Self-Monitored Blood Glucose (SMBG) Profile | Midday 2-HR PP (207, 195, 201, 203) | -50.38 milligrams/deciliter (mg/dL) | Standard Error 3.33 |
| Study B Q3D | Change From Baseline to 24 Weeks in 7-Point Self-Monitored Blood Glucose (SMBG) Profile | Evening Pre-Meal (214, 200, 214, 215) | -35.94 milligrams/deciliter (mg/dL) | Standard Error 3.21 |
| Study B Q3D | Change From Baseline to 24 Weeks in 7-Point Self-Monitored Blood Glucose (SMBG) Profile | Morning Pre-Meal (215, 200, 214, 219) | 0.85 milligrams/deciliter (mg/dL) | Standard Error 2.18 |
| Study B Q3D | Change From Baseline to 24 Weeks in 7-Point Self-Monitored Blood Glucose (SMBG) Profile | 0300 hour (3 am) (203, 192, 194, 193) | -13.39 milligrams/deciliter (mg/dL) | Standard Error 3.71 |
| Study B Q3D | Change From Baseline to 24 Weeks in 7-Point Self-Monitored Blood Glucose (SMBG) Profile | Bedtime (214, 200, 214, 216) | -43.52 milligrams/deciliter (mg/dL) | Standard Error 4 |
| Study B Q3D | Change From Baseline to 24 Weeks in 7-Point Self-Monitored Blood Glucose (SMBG) Profile | Midday Pre-Meal (214, 199, 213, 219) | -32.35 milligrams/deciliter (mg/dL) | Standard Error 2.52 |
p-value: 0.24595% CI: [-2.28, 8.93]Mixed Models Analysis
p-value: 0.84295% CI: [-7.71, 6.29]Mixed Models Analysis
p-value: 0.62695% CI: [-4.32, 7.16]Mixed Models Analysis
p-value: 0.35895% CI: [-10.91, 3.95]Mixed Models Analysis
p-value: 0.32295% CI: [-3.32, 10.07]Mixed Models Analysis
p-value: 0.61795% CI: [-11.08, 6.58]Mixed Models Analysis
p-value: 0.51995% CI: [-4.86, 9.6]Mixed Models Analysis
p-value: 0.41595% CI: [-2.96, 7.15]Mixed Models Analysis
p-value: 0.19895% CI: [-2.3, 11.06]Mixed Models Analysis
p-value: 0.04595% CI: [0.14, 12.29]Mixed Models Analysis
p-value: 0.42695% CI: [-4.5, 10.64]Mixed Models Analysis
p-value: 0.1495% CI: [-1.86, 13.17]Mixed Models Analysis
p-value: 0.0295% CI: [1.74, 20.63]Mixed Models Analysis
p-value: 0.03795% CI: [0.53, 17.49]Mixed Models Analysis
Secondary
Daily Dose of Insulin Per Kilogram of Body Weight: Total, Basal and Prandial (Bolus)
Total insulin was the sum of basal insulin (glargine) that was required to manage normal daily blood fluctuations and prandial insulin that was taken at meal time. Total, basal and prandial amounts were then divided by the participant's body weight in kilograms (kg). Least Squares (LS) mean calculated using mixed model repeating measure (MMRM) analysis that included baseline, treatment, country, sulfonylurea/meglitinide use, baseline glycated hemoglobin (HbA1c) strata (≤8% and \>8%), visit and treatment-by-visit interaction.
Time frame: 24 weeks
Population: Full Analysis Set: all participants who completed the lead-in period (if applicable), were randomized, received ≥1 dose of study insulin and with values in the specified category, except participants from the excluded site.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Study A Q1D | Daily Dose of Insulin Per Kilogram of Body Weight: Total, Basal and Prandial (Bolus) | Basal Insulin Dose (223, 213, 243, 239) | 0.68 international units/kilogram (IU/kg) | Standard Error 0.01 |
| Study A Q1D | Daily Dose of Insulin Per Kilogram of Body Weight: Total, Basal and Prandial (Bolus) | Total Insulin Dose (227, 213, 244, 242) | 1.12 international units/kilogram (IU/kg) | Standard Error 0.03 |
| Study A Q1D | Daily Dose of Insulin Per Kilogram of Body Weight: Total, Basal and Prandial (Bolus) | Bolus Insulin Dose (226, 213, 244, 241) | 0.48 international units/kilogram (IU/kg) | Standard Error 0.02 |
| Study A Q3D | Daily Dose of Insulin Per Kilogram of Body Weight: Total, Basal and Prandial (Bolus) | Basal Insulin Dose (223, 213, 243, 239) | 0.70 international units/kilogram (IU/kg) | Standard Error 0.01 |
| Study A Q3D | Daily Dose of Insulin Per Kilogram of Body Weight: Total, Basal and Prandial (Bolus) | Total Insulin Dose (227, 213, 244, 242) | 1.22 international units/kilogram (IU/kg) | Standard Error 0.03 |
| Study A Q3D | Daily Dose of Insulin Per Kilogram of Body Weight: Total, Basal and Prandial (Bolus) | Bolus Insulin Dose (226, 213, 244, 241) | 0.55 international units/kilogram (IU/kg) | Standard Error 0.03 |
| Study B Q1D | Daily Dose of Insulin Per Kilogram of Body Weight: Total, Basal and Prandial (Bolus) | Bolus Insulin Dose (226, 213, 244, 241) | 0.44 international units/kilogram (IU/kg) | Standard Error 0.02 |
| Study B Q1D | Daily Dose of Insulin Per Kilogram of Body Weight: Total, Basal and Prandial (Bolus) | Basal Insulin Dose (223, 213, 243, 239) | 0.64 international units/kilogram (IU/kg) | Standard Error 0.01 |
| Study B Q1D | Daily Dose of Insulin Per Kilogram of Body Weight: Total, Basal and Prandial (Bolus) | Total Insulin Dose (227, 213, 244, 242) | 1.09 international units/kilogram (IU/kg) | Standard Error 0.03 |
| Study B Q3D | Daily Dose of Insulin Per Kilogram of Body Weight: Total, Basal and Prandial (Bolus) | Basal Insulin Dose (223, 213, 243, 239) | 0.66 international units/kilogram (IU/kg) | Standard Error 0.01 |
| Study B Q3D | Daily Dose of Insulin Per Kilogram of Body Weight: Total, Basal and Prandial (Bolus) | Total Insulin Dose (227, 213, 244, 242) | 1.14 international units/kilogram (IU/kg) | Standard Error 0.03 |
| Study B Q3D | Daily Dose of Insulin Per Kilogram of Body Weight: Total, Basal and Prandial (Bolus) | Bolus Insulin Dose (226, 213, 244, 241) | 0.47 international units/kilogram (IU/kg) | Standard Error 0.02 |
p-value: 0.44295% CI: [-0.02, 0.05]LS Mean Difference
p-value: 0.03795% CI: [0, 0.14]Mixed Models Analysis
p-value: <0.00195% CI: [0.05, 0.16]Mixed Models Analysis
p-value: 0.27595% CI: [-0.01, 0.05]LS Mean Difference
p-value: 0.19495% CI: [-0.02, 0.08]Mixed Models Analysis
p-value: 0.24595% CI: [-0.04, 0.15]Mixed Models Analysis
Secondary
Daily Dose of Insulin: Total, Basal and Prandial (Bolus)
Total insulin was the sum of basal insulin (glargine) that was required to manage normal daily blood fluctuations and prandial insulin that was taken at meal time. Least Squares (LS) mean calculated using mixed model repeating measure (MMRM) analysis that included baseline, treatment, country, sulfonylurea/meglitinide use, baseline glycated hemoglobin (HbA1c) strata (≤8% and \>8%), visit and treatment-by-visit interaction.
Time frame: 24 weeks
Population: Full Analysis Set: all participants who completed the lead-in period (if applicable), were randomized, received ≥1 dose of study insulin and with values in the specified category, except participants from the excluded site.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Study A Q1D | Daily Dose of Insulin: Total, Basal and Prandial (Bolus) | Basal Insulin (223, 213, 243, 239) | 65.53 international units (IU) | Standard Error 1.41 |
| Study A Q1D | Daily Dose of Insulin: Total, Basal and Prandial (Bolus) | Total Insulin (227, 213, 244, 242) | 110.52 international units (IU) | Standard Error 3.32 |
| Study A Q1D | Daily Dose of Insulin: Total, Basal and Prandial (Bolus) | Prandial (Bolus) Insulin (226, 213, 244, 241) | 47.10 international units (IU) | Standard Error 2.82 |
| Study A Q3D | Daily Dose of Insulin: Total, Basal and Prandial (Bolus) | Basal Insulin (223, 213, 243, 239) | 66.67 international units (IU) | Standard Error 1.44 |
| Study A Q3D | Daily Dose of Insulin: Total, Basal and Prandial (Bolus) | Total Insulin (227, 213, 244, 242) | 119.38 international units (IU) | Standard Error 3.43 |
| Study A Q3D | Daily Dose of Insulin: Total, Basal and Prandial (Bolus) | Prandial (Bolus) Insulin (226, 213, 244, 241) | 53.81 international units (IU) | Standard Error 2.87 |
| Study B Q1D | Daily Dose of Insulin: Total, Basal and Prandial (Bolus) | Prandial (Bolus) Insulin (226, 213, 244, 241) | 43.03 international units (IU) | Standard Error 2.69 |
| Study B Q1D | Daily Dose of Insulin: Total, Basal and Prandial (Bolus) | Basal Insulin (223, 213, 243, 239) | 61.24 international units (IU) | Standard Error 1.16 |
| Study B Q1D | Daily Dose of Insulin: Total, Basal and Prandial (Bolus) | Total Insulin (227, 213, 244, 242) | 103.08 international units (IU) | Standard Error 3.53 |
| Study B Q3D | Daily Dose of Insulin: Total, Basal and Prandial (Bolus) | Basal Insulin (223, 213, 243, 239) | 62.33 international units (IU) | Standard Error 1.15 |
| Study B Q3D | Daily Dose of Insulin: Total, Basal and Prandial (Bolus) | Total Insulin (227, 213, 244, 242) | 109.13 international units (IU) | Standard Error 3.51 |
| Study B Q3D | Daily Dose of Insulin: Total, Basal and Prandial (Bolus) | Prandial (Bolus) Insulin (226, 213, 244, 241) | 48.40 international units (IU) | Standard Error 2.68 |
p-value: 0.54395% CI: [-2.55, 4.84]Mixed Models Analysis
p-value: 0.09595% CI: [-1.17, 14.6]Mixed Models Analysis
p-value: 0.05995% CI: [-0.35, 18.06]Mixed Models Analysis
p-value: 0.49795% CI: [-2.05, 4.23]Mixed Models Analysis
p-value: 0.15695% CI: [-2.06, 12.79]Mixed Models Analysis
p-value: 0.22295% CI: [-3.67, 15.76]Mixed Models Analysis
Secondary
Percentage of Participants ≥65 Years of Age Achieving Glycated Hemoglobin (HbA1c) Target Concentration
Percentage of participants ≥65 years of age achieving HbA1c target concentration of ≤7.0% or ≤6.5%.
Time frame: 24-week endpoint
Population: A subset of the Full Analysis Set: all participants who completed the lead-in period (if applicable), were randomized, received ≥1 dose of study insulin and were ≥65 years of age, except participants from the excluded site. Last observation carried forward (LOCF) was used.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Study A Q1D | Percentage of Participants ≥65 Years of Age Achieving Glycated Hemoglobin (HbA1c) Target Concentration | HbA1c ≤7% | 58.46 percentage of participants |
| Study A Q1D | Percentage of Participants ≥65 Years of Age Achieving Glycated Hemoglobin (HbA1c) Target Concentration | HbA1c ≤6.5% | 27.69 percentage of participants |
| Study A Q3D | Percentage of Participants ≥65 Years of Age Achieving Glycated Hemoglobin (HbA1c) Target Concentration | HbA1c ≤6.5% | 36.23 percentage of participants |
| Study A Q3D | Percentage of Participants ≥65 Years of Age Achieving Glycated Hemoglobin (HbA1c) Target Concentration | HbA1c ≤7% | 57.97 percentage of participants |
| Study B Q1D | Percentage of Participants ≥65 Years of Age Achieving Glycated Hemoglobin (HbA1c) Target Concentration | HbA1c ≤7% | 67.86 percentage of participants |
| Study B Q1D | Percentage of Participants ≥65 Years of Age Achieving Glycated Hemoglobin (HbA1c) Target Concentration | HbA1c ≤6.5% | 35.71 percentage of participants |
| Study B Q3D | Percentage of Participants ≥65 Years of Age Achieving Glycated Hemoglobin (HbA1c) Target Concentration | HbA1c ≤7% | 46.15 percentage of participants |
| Study B Q3D | Percentage of Participants ≥65 Years of Age Achieving Glycated Hemoglobin (HbA1c) Target Concentration | HbA1c ≤6.5% | 21.54 percentage of participants |
p-value: 0.70195% CI: [0.52, 2.67]Regression, Logistic
p-value: 0.24995% CI: [0.71, 3.7]Regression, Logistic
p-value: 0.01595% CI: [0.13, 0.8]Regression, Logistic
p-value: 0.07895% CI: [0.17, 1.1]Regression, Logistic
Secondary
Percentage of Participants Achieving Glycated Hemoglobin (HbA1c) Target Values
Percentage of participants who achieved HbA1c levels of ≤7.0% or ≤6.5%.
Time frame: 24-week endpoint
Population: Full Analysis Set: all participants who completed the lead-in period (if applicable), were randomized, received ≥1 dose of study insulin, except participants from the excluded site; last observation carried forward (LOCF) was used.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Study A Q1D | Percentage of Participants Achieving Glycated Hemoglobin (HbA1c) Target Values | HbA1c ≤6.5% | 26.22 percentage of participants |
| Study A Q1D | Percentage of Participants Achieving Glycated Hemoglobin (HbA1c) Target Values | HbA1c ≤7.0% | 49.81 percentage of participants |
| Study A Q3D | Percentage of Participants Achieving Glycated Hemoglobin (HbA1c) Target Values | HbA1c ≤7.0% | 42.53 percentage of participants |
| Study A Q3D | Percentage of Participants Achieving Glycated Hemoglobin (HbA1c) Target Values | HbA1c ≤6.5% | 23.37 percentage of participants |
| Study B Q1D | Percentage of Participants Achieving Glycated Hemoglobin (HbA1c) Target Values | HbA1c ≤7.0% | 49.31 percentage of participants |
| Study B Q1D | Percentage of Participants Achieving Glycated Hemoglobin (HbA1c) Target Values | HbA1c ≤6.5% | 25.00 percentage of participants |
| Study B Q3D | Percentage of Participants Achieving Glycated Hemoglobin (HbA1c) Target Values | HbA1c ≤6.5% | 22.76 percentage of participants |
| Study B Q3D | Percentage of Participants Achieving Glycated Hemoglobin (HbA1c) Target Values | HbA1c ≤7.0% | 42.41 percentage of participants |
p-value: 0.12895% CI: [0.52, 1.09]Regression, Logistic
p-value: 0.62595% CI: [0.58, 1.39]Regression, Logistic
p-value: 0.16295% CI: [0.53, 1.11]Regression, Logistic
p-value: 0.72395% CI: [0.61, 1.4]Regression, Linear
Secondary
Percentage of Participants With Severe Hypoglycemic Episodes
Severe hypoglycemia is defined as an event requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. These episodes may be associated with sufficient neuroglycopenia to induce seizure or coma. Plasma glucose measurements may not be available during such an event, but neurological recovery attributable to the restoration of plasma glucose to normal is considered sufficient evidence that the event was induced by low plasma glucose.
Time frame: Randomization up to 24 weeks
Population: All randomized participants except those from the excluded site.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Study A Q1D | Percentage of Participants With Severe Hypoglycemic Episodes | 1.9 percentage of participants |
| Study A Q3D | Percentage of Participants With Severe Hypoglycemic Episodes | 0.8 percentage of participants |
| Study B Q1D | Percentage of Participants With Severe Hypoglycemic Episodes | 2.4 percentage of participants |
| Study B Q3D | Percentage of Participants With Severe Hypoglycemic Episodes | 2.7 percentage of participants |
p-value: 0.258Regression, Logistic
p-value: 0.856Regression, Logistic
Secondary
The Number of Participants ≥65 Years of Age With Hypoglycemic Episodes (Incidence)
A hypoglycemic episode in participants ≥ 65 years of age was defined as any time a participant felt they were experiencing a sign or symptom that was associated with hypoglycemia, or had a blood glucose level of ≤70 milligram per deciliter \[mg/dL, ≤3.9 millimoles per liter (mmol/L)\] even if it was not associated with signs, symptoms or treatment (consistent with current American Diabetes Association 2005 guidelines).
Time frame: Randomization through 24 weeks overall
Population: All randomized participants ≥65 years old except those from the excluded site.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Study A Q1D | The Number of Participants ≥65 Years of Age With Hypoglycemic Episodes (Incidence) | 60 participants |
| Study A Q3D | The Number of Participants ≥65 Years of Age With Hypoglycemic Episodes (Incidence) | 61 participants |
| Study B Q1D | The Number of Participants ≥65 Years of Age With Hypoglycemic Episodes (Incidence) | 51 participants |
| Study B Q3D | The Number of Participants ≥65 Years of Age With Hypoglycemic Episodes (Incidence) | 53 participants |
p-value: 0.802Regression, Logistic
p-value: 0.205Regression, Logistic
Secondary
The Number of Participants With a Hypoglycemic Episode (Incidence)
A hypoglycemic episode was defined as any time a participant felt they were experiencing a sign or symptom that was associated with hypoglycemia, or had a blood glucose level of ≤70 milligram per deciliter \[mg/dL, ≤3.9 millimoles per liter (mmol/L)\] even if it was not associated with signs, symptoms or treatment (consistent with current American Diabetes Association 2005 guidelines).
Time frame: Randomization through 24 weeks overall
Population: All randomized participants except from the excluded site.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Study A Q1D | The Number of Participants With a Hypoglycemic Episode (Incidence) | 231 participants |
| Study A Q3D | The Number of Participants With a Hypoglycemic Episode (Incidence) | 218 participants |
| Study B Q1D | The Number of Participants With a Hypoglycemic Episode (Incidence) | 238 participants |
| Study B Q3D | The Number of Participants With a Hypoglycemic Episode (Incidence) | 231 participants |
p-value: 0.435Regression, Logistic
p-value: 0.351Regression, Logistic
Secondary
The Rate of Hypoglycemic Episodes
The hypoglycemia rate per 30 days was calculated as the number of hypoglycemic episodes reported divided by the number of days at risk times 30.
Time frame: Randomization through 24 weeks overall
Population: All randomized participants except those from the excluded site.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Study A Q1D | The Rate of Hypoglycemic Episodes | 3.15 hypoglycemic episodes per 30 day period | Standard Deviation 0.23 |
| Study A Q3D | The Rate of Hypoglycemic Episodes | 3.33 hypoglycemic episodes per 30 day period | Standard Deviation 0.25 |
| Study B Q1D | The Rate of Hypoglycemic Episodes | 3.18 hypoglycemic episodes per 30 day period | Standard Deviation 0.26 |
| Study B Q3D | The Rate of Hypoglycemic Episodes | 3.33 hypoglycemic episodes per 30 day period | Standard Deviation 0.27 |
p-value: 0.58695% CI: [0.86, 1.3]Negative Binomial Regression
p-value: 0.68995% CI: [0.84, 1.3]Negative Binomial
Secondary
Time to Reach Glycated Hemoglobin (HbA1c) Target Values
Percentage of participants is the number of participants who achieved HbA1c target values of ≤6.5% or ≤7.0% during the specified time period divided by the total number of participants who did not discontinue from the study but had not reached HbA1c target at the beginning of the specified post baseline time period (≤100 days and ≥101 days). Participants who did not experience an outcome before discontinuation or completion of the study were censored using the date of discontinuation. Participants who were lost to follow up the date of discontinuation were considered to be the date of last contact.
Time frame: Baseline through 24 weeks
Population: Full Analysis Set: all participants who completed the lead-in period (if applicable), were randomized, received ≥1 dose of study insulin, except participants from the excluded site. Censored participants: Study A: ≤6.5% Q1D=186 and Q3D=197; Study A ≤7.0% Q1D=120 and Q3D=134; Study B: ≤6.5% Q1D=206 and Q3D=212, Study B ≤7.0% Q1D=135 and Q3D=152.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Study A Q1D | Time to Reach Glycated Hemoglobin (HbA1c) Target Values | HbA1c ≤6.5% Post-Baseline ≤100 days | 19.48 percentage of participants |
| Study A Q1D | Time to Reach Glycated Hemoglobin (HbA1c) Target Values | HbA1c ≤6.5% ≥101 days post-baseline | 14.80 percentage of participants |
| Study A Q1D | Time to Reach Glycated Hemoglobin (HbA1c) Target Values | HbA1c ≤7.0% Post-Baseline ≤100 days | 37.45 percentage of participants |
| Study A Q1D | Time to Reach Glycated Hemoglobin (HbA1c) Target Values | HbA1c ≤7.0% ≥101 days post-baseline | 31.54 percentage of participants |
| Study A Q3D | Time to Reach Glycated Hemoglobin (HbA1c) Target Values | HbA1c ≤6.5% ≥101 days post-baseline | 18.00 percentage of participants |
| Study A Q3D | Time to Reach Glycated Hemoglobin (HbA1c) Target Values | HbA1c ≤7.0% Post-Baseline ≤100 days | 33.72 percentage of participants |
| Study A Q3D | Time to Reach Glycated Hemoglobin (HbA1c) Target Values | HbA1c ≤7.0% ≥101 days post-baseline | 26.90 percentage of participants |
| Study A Q3D | Time to Reach Glycated Hemoglobin (HbA1c) Target Values | HbA1c ≤6.5% Post-Baseline ≤100 days | 10.73 percentage of participants |
| Study B Q1D | Time to Reach Glycated Hemoglobin (HbA1c) Target Values | HbA1c ≤7.0% Post-Baseline ≤100 days | 37.15 percentage of participants |
| Study B Q1D | Time to Reach Glycated Hemoglobin (HbA1c) Target Values | HbA1c ≤6.5% ≥101 days post-baseline | 14.81 percentage of participants |
| Study B Q1D | Time to Reach Glycated Hemoglobin (HbA1c) Target Values | HbA1c ≤7.0% ≥101 days post-baseline | 28.75 percentage of participants |
| Study B Q1D | Time to Reach Glycated Hemoglobin (HbA1c) Target Values | HbA1c ≤6.5% Post-Baseline ≤100 days | 17.36 percentage of participants |
| Study B Q3D | Time to Reach Glycated Hemoglobin (HbA1c) Target Values | HbA1c ≤7.0% ≥101 days post-baseline | 24.56 percentage of participants |
| Study B Q3D | Time to Reach Glycated Hemoglobin (HbA1c) Target Values | HbA1c ≤6.5% ≥101 days post-baseline | 16.14 percentage of participants |
| Study B Q3D | Time to Reach Glycated Hemoglobin (HbA1c) Target Values | HbA1c ≤6.5% Post-Baseline ≤100 days | 14.48 percentage of participants |
| Study B Q3D | Time to Reach Glycated Hemoglobin (HbA1c) Target Values | HbA1c ≤7.0% Post-Baseline ≤100 days | 33.10 percentage of participants |
p-value: 0.18295% CI: [0.57, 1.11]Regression, Cox
p-value: 0.4695% CI: [0.65, 1.22]Regression, Cox