Diabetes Mellitus, Type 2
Conditions
Brief summary
The main purpose of this study is to compare the effectiveness of Human Regular U-500 Insulin three times a day versus twice a day.
Interventions
DRUGHuman Regular U-500 Insulin
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 75 Years
Healthy volunteers
No
Inclusion criteria
Major Inclusion Criteria: * Have type 2 diabetes mellitus (World Health Organization \[WHO\] Classification of Diabetes) * Have a body mass index (BMI) ≥25 kilogram per square meter (kg/m\^2) * Have Glycated Hemoglobin A1c (HbA1c) ≥7.5% and ≤12.0%, as measured by the central laboratory at entry * Current U-100 insulin/analogue users on \>200 and ≤600 units per day for ≥3 months at study entry and reconfirmed at randomization * Have a history of stable body weight for at least 3 months prior to study entry * Concomitant medications may include metformin (MET), dipeptidyl peptidase-4 (DPP-4) inhibitors approved for use with insulin at time of study entry (for example, sitagliptin, saxagliptin, and linagliptin), pioglitazone, and/or sulfonylureas (SUs)/glinides (repaglinide or nateglinide). Participant's oral antihyperglycemic drug (OAD) dose(s) must have been stable for ≥3 months Major
Exclusion criteria
* Have type 1 diabetes mellitus or other types of diabetes mellitus apart from type 2 diabetes mellitus * Have obvious clinical signs or symptoms of liver disease, acute or chronic hepatitis, or alanine aminotransferase or aspartate aminotransferase levels ≥3 times the upper limit of the reference range * Have chronic kidney disease stage 4 and higher or history of renal transplantation * Have history of more than 1 episode of severe hypoglycemia within the 6 months prior to study entry * Have received insulin by continuous subcutaneous insulin infusion in the 3 months prior to study entry * Have received U-500R in the 3 months prior to study entry * Have had a blood transfusion or severe blood loss within 3 months prior to study entry or have known hemoglobinopathy, hemolytic anemia, or sickle cell anemia * Are taking chronic systemic glucocorticoid therapy or have received such therapy within the 4 weeks immediately prior to study entry * Have an irregular sleep/wake cycle * Have used rosiglitazone, once- or twice-daily glucagon-like peptide-1 (GLP-1) receptor agents, pramlintide, or other injectable or oral antihyperglycemic therapy not listed in the inclusion criteria in the 3 months prior to study entry. Participants may not have used once-weekly GLP-1 receptor agents in the 4 months prior to study entry * Have used any weight loss drugs in the 3 months prior to study entry * Have a history of bariatric surgery * Have a history of malignancy other than basal cell or squamous cell skin cancer * Have New York Heart Association (NYHA) Class III or IV per NYHA Cardiac Disease Functional Classification * Are breastfeeding or pregnant, or intend to become pregnant during the course of the study, or are sexually active women of childbearing potential not actively practicing birth control by a method determined by the investigator to be medically acceptable
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 24 in Glycated Hemoglobin A1c (HbA1c) | Baseline, Week 24 | Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with investigator, baseline total daily dose (TDD; ≤300 or \>300 units), treatment (TID or BID), visit, and treatment-by-visit interaction as fixed effects and baseline HbA1c as a covariate. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 30-Day Adjusted Rate of Hypoglycemic Events | Baseline through Week 24 | Hypoglycemic events (HE) were classified as severe (an event requiring assistance from another person \[accompanied by neurologic/cognitive impairment\]), documented symptomatic (an event which is associated with signs/symptoms of hypoglycemia and plasma glucose \[PG\] ≤70 milligrams per deciliter \[mg/dL\]), documented symptomatic nocturnal (any documented symptomatic HE that occurred between bedtime and waking), or asymptomatic (any measured PG ≤70 mg/dL not accompanied by hypoglycemic signs/symptoms). The 30-day adjusted rate of HE is summarized cumulatively at 24 weeks. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. |
| Change From Baseline to Week 24 in Body Weight | Baseline, Week 24 | LS means of change from baseline were calculated using MMRM with investigator, baseline HbA1c (≤8% or \>8%), baseline TDD (≤300 or \>300 units), treatment (TID or BID), visit, and treatment-by-visit interaction as fixed effects and baseline body weight as a covariate. |
| Change From Baseline to Week 24 in Total Daily Dose (TDD; Units) of Insulin | Baseline, Week 24 | Baseline TDD was defined as the last U-100 insulin TDD prior to receiving the first dose of U-500R insulin. LS means of change from baseline were calculated using MMRM with investigator, baseline HbA1c (≤8% or \>8%), treatment (TID or BID), visit, and treatment-by-visit interaction as fixed effects and baseline TDD as a covariate. |
| Change From Baseline to Week 24 in Total Daily Dose (TDD; Units/kg) of Insulin | Baseline, Week 24 | Baseline TDD was defined as the last U-100 insulin TDD prior to receiving the first dose of U-500R insulin. LS means of change from baseline were calculated using MMRM with investigator, baseline HbA1c (≤8% or \>8%), treatment (TID or BID), visit, and treatment-by-visit interaction as fixed effects and baseline TDD as a covariate. |
| Change From Baseline to Week 24 in Fasting Plasma Glucose (FPG) Levels | Baseline, Week 24 | LS means of change from baseline were calculated using MMRM with investigator, baseline HbA1c (≤8% or \>8%), baseline TDD (≤300 or \>300 units), treatment (TID or BID), visit, and treatment-by-visit interaction as fixed effects and baseline FPG as a covariate. |
| Time to Reach HbA1c Target Values | Baseline through 6, 12, 18, and 24 weeks. | The cumulative number of participants achieving an HbA1c of ≤6.5%, \<7.0%, \<7.5%, and \<8.0% is summarized at Weeks 6, 12, 18, and 24. The number of participants at risk (n) is also provided for each target value and timepoint. |
| Percentage of Participants Achieving HbA1c of ≤6.5%, <7.0%, <7.5%, and <8.0% at Week 24 | Week 24 | The percentage of participants achieving an HbA1c of ≤6.5%, \<7.0%, \<7.5%, and \<8.0% at Week 24 was calculated by the dividing the number of participants meeting the criteria by the total number of participants analyzed, multiplied by 100. |
| Change From Baseline to Week 24 in Number of Insulin Injections | Baseline, Week 24 | The number of insulin injections per day at baseline (Week 0) and at Week 24 are presented. |
| Mean Change From Baseline to Week 24 in 7-Point Self-Monitored Blood Glucose (SMBG) | Baseline, Week 24 | The 7-point SMBG is a participant self-administered blood glucose test which utilizes measurements at specific time points over a 24-hour period, including pre-morning meal (fasting), 2 hours after morning meal, pre-midday meal, 2 hours after midday meal, pre-evening meal, 2 hours after evening meal, and 3 AM. LS means of change from baseline were calculated using MMRM with investigator, baseline HbA1c (≤8% or \>8%), baseline TDD (≤300 or \>300 units), treatment (TID or BID), visit, and treatment-by-visit interaction as fixed effects and baseline SMBG as a covariate. |
| Change From Baseline to Week 24 in HbA1c Based on Baseline TDD Insulin ≤2.0 Units/kg and >2.0 Units/kg | Baseline, Week 24 | Participants were stratified by their baseline TDD insulin (≤2.0 units/kg or \>2.0 units/kg). LS means of change from baseline were calculated using MMRM with investigator, baseline TDD (≤300 or \>300 units), treatment (TID or BID), visit, and treatment-by-visit interaction as fixed effects and baseline HbA1c as a covariate. |
| Change From Baseline to Week 24 in 30-Day Adjusted Rate of Hypoglycemic Events Based on Baseline TDD Insulin ≤2.0 Units/kg and >2.0 Units/kg | Baseline, Week 24 | Participants were stratified by their baseline TDD insulin (≤2.0 units/kg or \>2.0 units/kg). Hypoglycemic events (HE) were classified as severe (an event requiring assistance from another person \[accompanied by neurologic/cognitive impairment\]), documented symptomatic (DS; an event which is associated with signs/symptoms of hypoglycemia and plasma glucose \[PG\] ≤70 milligrams per deciliter \[mg/dL\]), or nocturnal (Noc; any documented symptomatic HE that occurred between bedtime and waking). The 30-day adjusted rate of HE is summarized cumulatively at 24 weeks. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. |
| Change From Baseline to Week 24 in Percentage of Participants With Hypoglycemic Events Based on Baseline TDD Insulin ≥2.0 Units/kg and <2.0 Units/kg | Baseline, Week 24 | Participants were stratified by their baseline TDD insulin (≤2.0 units (U)/kg or \>2.0 U/kg). The percentage of participants at risk of developing hypoglycemia (including documented symptomatic, asymptomatic, probable symptomatic, unspecified, or severe hypoglycemia) is presented at Baseline and at Week 24 and was calculated using MMRM fit with options of the binomial distribution and log link function including treatment, TDD (\>300 units or ≤300 units), pioglitazone use (yes or no), visit, and treatment-by-visit interaction as fixed effects, and baseline HbA1c value as a covariate. |
| Change From Baseline to Week 24 in Body Weight Based on Baseline TDD Insulin ≥2.0 Units/kg and <2.0 Units/kg | Baseline, Week 24 | Participants were stratified by their baseline TDD insulin (≤2.0 units/kg or \>2.0 units/kg). LS means of change from baseline were calculated using MMRM with investigator, baseline HbA1c (≤8% or \>8%), baseline TDD (≤300 or \>300 units), treatment (TID or BID), visit, and treatment-by-visit interaction as fixed effects and baseline body weight as a covariate. |
| Percentage of Participants With Hypoglycemic Events | Baseline through Week 24 | Hypoglycemic events (HE) were classified as severe (an event requiring assistance from another person \[accompanied by neurologic/cognitive impairment\]), documented symptomatic (an event which is associated with signs/symptoms of hypoglycemia and plasma glucose \[PG\] ≤70 milligrams per deciliter \[mg/dL\]), documented symptomatic nocturnal (any documented symptomatic HE that occurred between bedtime and waking), or asymptomatic (any measured PG ≤70 mg/dL not accompanied by hypoglycemic signs/symptoms). The percentage of participants with HE at 24 weeks was calculated by the dividing the number of participants meeting the criteria by the total number of participants analyzed, multiplied by 100. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. |
Countries
Puerto Rico, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Human Regular U-500 Insulin TID U-500R Insulin titrated based on blood glucose readings, administered SC, TID for 24 weeks. | 162 |
| Human Regular U-500 Insulin BID U-500R Insulin titrated based on blood glucose readings, administered SC, BID for 24 weeks. | 163 |
| Total | 325 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 4 |
| Overall Study | Death | 0 | 1 |
| Overall Study | Lost to Follow-up | 1 | 3 |
| Overall Study | Physician Decision | 5 | 1 |
| Overall Study | Protocol Violation | 14 | 13 |
| Overall Study | Sponsor Decision | 0 | 2 |
| Overall Study | Withdrawal by Subject | 6 | 11 |
Baseline characteristics
| Characteristic | Human Regular U-500 Insulin TID | Total | Human Regular U-500 Insulin BID |
|---|---|---|---|
| Age, Continuous | 55.31 years STANDARD_DEVIATION 10.51 | 55.41 years STANDARD_DEVIATION 9.78 | 55.50 years STANDARD_DEVIATION 9.03 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 32 Participants | 62 Participants | 30 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 130 Participants | 263 Participants | 133 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants | 4 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 6 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 21 Participants | 40 Participants | 19 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 7 Participants | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 133 Participants | 266 Participants | 133 Participants |
| Region of Enrollment Puerto Rico | 16 participants | 30 participants | 14 participants |
| Region of Enrollment United States | 146 participants | 295 participants | 149 participants |
| Sex: Female, Male Female | 79 Participants | 153 Participants | 74 Participants |
| Sex: Female, Male Male | 83 Participants | 172 Participants | 89 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 80 / 162 | 94 / 163 |
| serious Total, serious adverse events | 28 / 162 | 27 / 163 |
Outcome results
Primary
Change From Baseline to Week 24 in Glycated Hemoglobin A1c (HbA1c)
Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with investigator, baseline total daily dose (TDD; ≤300 or \>300 units), treatment (TID or BID), visit, and treatment-by-visit interaction as fixed effects and baseline HbA1c as a covariate.
Time frame: Baseline, Week 24
Population: Randomized participants who received at least 1 dose of U-500R with evaluable HbA1c data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Human Regular U-500 Insulin TID | Change From Baseline to Week 24 in Glycated Hemoglobin A1c (HbA1c) | -1.12 percentage of HbA1c | Standard Error 0.08 |
| Human Regular U-500 Insulin BID | Change From Baseline to Week 24 in Glycated Hemoglobin A1c (HbA1c) | -1.22 percentage of HbA1c | Standard Error 0.08 |
Comparison: Approximately 325 participants were to be randomized (in a 1:1 ratio of U-500R insulin TID:BID) and 260 were to complete the study (with a 20% dropout rate). The 260 completers would provide a 66.4% chance to show equivalence of TID and BID algorithms, 14.4% chance to show noninferiority of TID, 2.5% chance to superiority of TID, 14.4% chance to show noninferiority of BID, and 2.5% chance to show superiority of BID, assuming a difference in HbA1c change of 0% and a standard deviation of 1.1%.p-value: 0.370995% CI: [-0.33, 0.12]Mixed Models Analysis
Secondary
30-Day Adjusted Rate of Hypoglycemic Events
Hypoglycemic events (HE) were classified as severe (an event requiring assistance from another person \[accompanied by neurologic/cognitive impairment\]), documented symptomatic (an event which is associated with signs/symptoms of hypoglycemia and plasma glucose \[PG\] ≤70 milligrams per deciliter \[mg/dL\]), documented symptomatic nocturnal (any documented symptomatic HE that occurred between bedtime and waking), or asymptomatic (any measured PG ≤70 mg/dL not accompanied by hypoglycemic signs/symptoms). The 30-day adjusted rate of HE is summarized cumulatively at 24 weeks. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Time frame: Baseline through Week 24
Population: Randomized participants who received at least 1 dose of U-500R.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Human Regular U-500 Insulin TID | 30-Day Adjusted Rate of Hypoglycemic Events | Documented Symptomatic HE | 3.343 events per participant per 30 days | Standard Deviation 3.174 |
| Human Regular U-500 Insulin TID | 30-Day Adjusted Rate of Hypoglycemic Events | Documented Symptomatic Nocturnal HE | 1.013 events per participant per 30 days | Standard Deviation 1.438 |
| Human Regular U-500 Insulin TID | 30-Day Adjusted Rate of Hypoglycemic Events | Asymptomatic HE | 1.340 events per participant per 30 days | Standard Deviation 3.215 |
| Human Regular U-500 Insulin TID | 30-Day Adjusted Rate of Hypoglycemic Events | Severe HE | 0.004 events per participant per 30 days | Standard Deviation 0.028 |
| Human Regular U-500 Insulin BID | 30-Day Adjusted Rate of Hypoglycemic Events | Severe HE | 0.009 events per participant per 30 days | Standard Deviation 0.053 |
| Human Regular U-500 Insulin BID | 30-Day Adjusted Rate of Hypoglycemic Events | Documented Symptomatic HE | 3.885 events per participant per 30 days | Standard Deviation 3.448 |
| Human Regular U-500 Insulin BID | 30-Day Adjusted Rate of Hypoglycemic Events | Asymptomatic HE | 1.028 events per participant per 30 days | Standard Deviation 2.231 |
| Human Regular U-500 Insulin BID | 30-Day Adjusted Rate of Hypoglycemic Events | Documented Symptomatic Nocturnal HE | 1.299 events per participant per 30 days | Standard Deviation 1.54 |
Secondary
Change From Baseline to Week 24 in 30-Day Adjusted Rate of Hypoglycemic Events Based on Baseline TDD Insulin ≤2.0 Units/kg and >2.0 Units/kg
Participants were stratified by their baseline TDD insulin (≤2.0 units/kg or \>2.0 units/kg). Hypoglycemic events (HE) were classified as severe (an event requiring assistance from another person \[accompanied by neurologic/cognitive impairment\]), documented symptomatic (DS; an event which is associated with signs/symptoms of hypoglycemia and plasma glucose \[PG\] ≤70 milligrams per deciliter \[mg/dL\]), or nocturnal (Noc; any documented symptomatic HE that occurred between bedtime and waking). The 30-day adjusted rate of HE is summarized cumulatively at 24 weeks. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Time frame: Baseline, Week 24
Population: Randomized participants who received at least 1 dose of U-500R.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Human Regular U-500 Insulin TID | Change From Baseline to Week 24 in 30-Day Adjusted Rate of Hypoglycemic Events Based on Baseline TDD Insulin ≤2.0 Units/kg and >2.0 Units/kg | Severe HE, TDD ≤2 units/kg, Baseline (n=50, 46) | 0 events per participant per 30 days | Standard Deviation 0 |
| Human Regular U-500 Insulin TID | Change From Baseline to Week 24 in 30-Day Adjusted Rate of Hypoglycemic Events Based on Baseline TDD Insulin ≤2.0 Units/kg and >2.0 Units/kg | Severe HE, TDD ≤2 units/kg, Week 24 (n=50, 46) | 0.004 events per participant per 30 days | Standard Deviation 0.025 |
| Human Regular U-500 Insulin TID | Change From Baseline to Week 24 in 30-Day Adjusted Rate of Hypoglycemic Events Based on Baseline TDD Insulin ≤2.0 Units/kg and >2.0 Units/kg | Severe HE, TDD >2 units/kg, Baseline (n=112, 115) | 0 events per participant per 30 days | Standard Deviation 0 |
| Human Regular U-500 Insulin TID | Change From Baseline to Week 24 in 30-Day Adjusted Rate of Hypoglycemic Events Based on Baseline TDD Insulin ≤2.0 Units/kg and >2.0 Units/kg | Severe HE, TDD >2 units/kg, Week 24 (n=112, 115) | 0.004 events per participant per 30 days | Standard Deviation 0.029 |
| Human Regular U-500 Insulin TID | Change From Baseline to Week 24 in 30-Day Adjusted Rate of Hypoglycemic Events Based on Baseline TDD Insulin ≤2.0 Units/kg and >2.0 Units/kg | DS HE, TDD ≤2 units/kg, Baseline (n=50, 46) | 1.958 events per participant per 30 days | Standard Deviation 4.808 |
| Human Regular U-500 Insulin TID | Change From Baseline to Week 24 in 30-Day Adjusted Rate of Hypoglycemic Events Based on Baseline TDD Insulin ≤2.0 Units/kg and >2.0 Units/kg | DS HE, TDD ≤2 units/kg, Week 24 (n=50, 46)) | 2.356 events per participant per 30 days | Standard Deviation 2.352 |
| Human Regular U-500 Insulin TID | Change From Baseline to Week 24 in 30-Day Adjusted Rate of Hypoglycemic Events Based on Baseline TDD Insulin ≤2.0 Units/kg and >2.0 Units/kg | DS HE, TDD >2 units/kg, Baseline (n=112, 115) | 2.037 events per participant per 30 days | Standard Deviation 4.382 |
| Human Regular U-500 Insulin TID | Change From Baseline to Week 24 in 30-Day Adjusted Rate of Hypoglycemic Events Based on Baseline TDD Insulin ≤2.0 Units/kg and >2.0 Units/kg | DS HE, TDD >2 units/kg, Week 24 (n=112, 115) | 3.784 events per participant per 30 days | Standard Deviation 3.397 |
| Human Regular U-500 Insulin TID | Change From Baseline to Week 24 in 30-Day Adjusted Rate of Hypoglycemic Events Based on Baseline TDD Insulin ≤2.0 Units/kg and >2.0 Units/kg | Noc. HE, TDD ≤2 units/kg, Baseline (n=50, 46) | 1.066 events per participant per 30 days | Standard Deviation 2.045 |
| Human Regular U-500 Insulin TID | Change From Baseline to Week 24 in 30-Day Adjusted Rate of Hypoglycemic Events Based on Baseline TDD Insulin ≤2.0 Units/kg and >2.0 Units/kg | Noc. HE, TDD ≤2 units/kg, Week 24 (n=50, 46) | 1.105 events per participant per 30 days | Standard Deviation 1.153 |
| Human Regular U-500 Insulin TID | Change From Baseline to Week 24 in 30-Day Adjusted Rate of Hypoglycemic Events Based on Baseline TDD Insulin ≤2.0 Units/kg and >2.0 Units/kg | Noc. HE, TDD >2 units/kg, Baseline (n=112, 115) | 0.792 events per participant per 30 days | Standard Deviation 2.465 |
| Human Regular U-500 Insulin TID | Change From Baseline to Week 24 in 30-Day Adjusted Rate of Hypoglycemic Events Based on Baseline TDD Insulin ≤2.0 Units/kg and >2.0 Units/kg | Noc. HE, TDD >2 units/kg, Week 24 (n=112, 115) | 1.522 events per participant per 30 days | Standard Deviation 2.018 |
| Human Regular U-500 Insulin BID | Change From Baseline to Week 24 in 30-Day Adjusted Rate of Hypoglycemic Events Based on Baseline TDD Insulin ≤2.0 Units/kg and >2.0 Units/kg | Noc. HE, TDD >2 units/kg, Baseline (n=112, 115) | 0.585 events per participant per 30 days | Standard Deviation 1.445 |
| Human Regular U-500 Insulin BID | Change From Baseline to Week 24 in 30-Day Adjusted Rate of Hypoglycemic Events Based on Baseline TDD Insulin ≤2.0 Units/kg and >2.0 Units/kg | Severe HE, TDD ≤2 units/kg, Baseline (n=50, 46) | 0 events per participant per 30 days | Standard Deviation 0 |
| Human Regular U-500 Insulin BID | Change From Baseline to Week 24 in 30-Day Adjusted Rate of Hypoglycemic Events Based on Baseline TDD Insulin ≤2.0 Units/kg and >2.0 Units/kg | DS HE, TDD >2 units/kg, Baseline (n=112, 115) | 1.730 events per participant per 30 days | Standard Deviation 3.18 |
| Human Regular U-500 Insulin BID | Change From Baseline to Week 24 in 30-Day Adjusted Rate of Hypoglycemic Events Based on Baseline TDD Insulin ≤2.0 Units/kg and >2.0 Units/kg | Severe HE, TDD ≤2 units/kg, Week 24 (n=50, 46) | 0 events per participant per 30 days | Standard Deviation 0 |
| Human Regular U-500 Insulin BID | Change From Baseline to Week 24 in 30-Day Adjusted Rate of Hypoglycemic Events Based on Baseline TDD Insulin ≤2.0 Units/kg and >2.0 Units/kg | Noc. HE, TDD ≤2 units/kg, Week 24 (n=50, 46) | 1.282 events per participant per 30 days | Standard Deviation 1.431 |
| Human Regular U-500 Insulin BID | Change From Baseline to Week 24 in 30-Day Adjusted Rate of Hypoglycemic Events Based on Baseline TDD Insulin ≤2.0 Units/kg and >2.0 Units/kg | Severe HE, TDD >2 units/kg, Baseline (n=112, 115) | 0 events per participant per 30 days | Standard Deviation 0 |
| Human Regular U-500 Insulin BID | Change From Baseline to Week 24 in 30-Day Adjusted Rate of Hypoglycemic Events Based on Baseline TDD Insulin ≤2.0 Units/kg and >2.0 Units/kg | DS HE, TDD >2 units/kg, Week 24 (n=112, 115) | 4.186 events per participant per 30 days | Standard Deviation 3.509 |
| Human Regular U-500 Insulin BID | Change From Baseline to Week 24 in 30-Day Adjusted Rate of Hypoglycemic Events Based on Baseline TDD Insulin ≤2.0 Units/kg and >2.0 Units/kg | Severe HE, TDD >2 units/kg, Week 24 (n=112, 115) | 0.013 events per participant per 30 days | Standard Deviation 0.062 |
| Human Regular U-500 Insulin BID | Change From Baseline to Week 24 in 30-Day Adjusted Rate of Hypoglycemic Events Based on Baseline TDD Insulin ≤2.0 Units/kg and >2.0 Units/kg | Noc. HE, TDD >2 units/kg, Week 24 (n=112, 115) | 1.753 events per participant per 30 days | Standard Deviation 1.934 |
| Human Regular U-500 Insulin BID | Change From Baseline to Week 24 in 30-Day Adjusted Rate of Hypoglycemic Events Based on Baseline TDD Insulin ≤2.0 Units/kg and >2.0 Units/kg | DS HE, TDD ≤2 units/kg, Baseline (n=50, 46) | 1.454 events per participant per 30 days | Standard Deviation 3.251 |
| Human Regular U-500 Insulin BID | Change From Baseline to Week 24 in 30-Day Adjusted Rate of Hypoglycemic Events Based on Baseline TDD Insulin ≤2.0 Units/kg and >2.0 Units/kg | Noc. HE, TDD ≤2 units/kg, Baseline (n=50, 46) | 0.711 events per participant per 30 days | Standard Deviation 1.965 |
| Human Regular U-500 Insulin BID | Change From Baseline to Week 24 in 30-Day Adjusted Rate of Hypoglycemic Events Based on Baseline TDD Insulin ≤2.0 Units/kg and >2.0 Units/kg | DS HE, TDD ≤2 units/kg, Week 24 (n=50, 46)) | 3.131 events per participant per 30 days | Standard Deviation 3.204 |
Secondary
Change From Baseline to Week 24 in Body Weight
LS means of change from baseline were calculated using MMRM with investigator, baseline HbA1c (≤8% or \>8%), baseline TDD (≤300 or \>300 units), treatment (TID or BID), visit, and treatment-by-visit interaction as fixed effects and baseline body weight as a covariate.
Time frame: Baseline, Week 24
Population: Randomized participants who received at least 1 dose of U-500R with evaluable body weight data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Human Regular U-500 Insulin TID | Change From Baseline to Week 24 in Body Weight | 5.44 kilograms (kg) | Standard Error 0.41 |
| Human Regular U-500 Insulin BID | Change From Baseline to Week 24 in Body Weight | 4.88 kilograms (kg) | Standard Error 0.41 |
Secondary
Change From Baseline to Week 24 in Body Weight Based on Baseline TDD Insulin ≥2.0 Units/kg and <2.0 Units/kg
Participants were stratified by their baseline TDD insulin (≤2.0 units/kg or \>2.0 units/kg). LS means of change from baseline were calculated using MMRM with investigator, baseline HbA1c (≤8% or \>8%), baseline TDD (≤300 or \>300 units), treatment (TID or BID), visit, and treatment-by-visit interaction as fixed effects and baseline body weight as a covariate.
Time frame: Baseline, Week 24
Population: Randomized participants who received at least 1 dose of U-500R with evaluable body weight data.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Human Regular U-500 Insulin TID | Change From Baseline to Week 24 in Body Weight Based on Baseline TDD Insulin ≥2.0 Units/kg and <2.0 Units/kg | Baseline TDD insulin ≤2.0 units/kg (n=50, 46) | 6.11 kg | Standard Error 0.88 |
| Human Regular U-500 Insulin TID | Change From Baseline to Week 24 in Body Weight Based on Baseline TDD Insulin ≥2.0 Units/kg and <2.0 Units/kg | Baseline TDD insulin >2.0 units/kg (n=112, 115) | 5.08 kg | Standard Error 0.44 |
| Human Regular U-500 Insulin BID | Change From Baseline to Week 24 in Body Weight Based on Baseline TDD Insulin ≥2.0 Units/kg and <2.0 Units/kg | Baseline TDD insulin ≤2.0 units/kg (n=50, 46) | 6.09 kg | Standard Error 0.93 |
| Human Regular U-500 Insulin BID | Change From Baseline to Week 24 in Body Weight Based on Baseline TDD Insulin ≥2.0 Units/kg and <2.0 Units/kg | Baseline TDD insulin >2.0 units/kg (n=112, 115) | 4.40 kg | Standard Error 0.43 |
Secondary
Change From Baseline to Week 24 in Fasting Plasma Glucose (FPG) Levels
LS means of change from baseline were calculated using MMRM with investigator, baseline HbA1c (≤8% or \>8%), baseline TDD (≤300 or \>300 units), treatment (TID or BID), visit, and treatment-by-visit interaction as fixed effects and baseline FPG as a covariate.
Time frame: Baseline, Week 24
Population: Randomized participants who received at least 1 dose of U-500R with evaluable FPG data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Human Regular U-500 Insulin TID | Change From Baseline to Week 24 in Fasting Plasma Glucose (FPG) Levels | -6.66 milligrams per deciliter (mg/dL) | Standard Error 5.64 |
| Human Regular U-500 Insulin BID | Change From Baseline to Week 24 in Fasting Plasma Glucose (FPG) Levels | -8.86 milligrams per deciliter (mg/dL) | Standard Error 5.72 |
Secondary
Change From Baseline to Week 24 in HbA1c Based on Baseline TDD Insulin ≤2.0 Units/kg and >2.0 Units/kg
Participants were stratified by their baseline TDD insulin (≤2.0 units/kg or \>2.0 units/kg). LS means of change from baseline were calculated using MMRM with investigator, baseline TDD (≤300 or \>300 units), treatment (TID or BID), visit, and treatment-by-visit interaction as fixed effects and baseline HbA1c as a covariate.
Time frame: Baseline, Week 24
Population: Randomized participants who received at least 1 dose of U-500R with evaluable HbA1c data.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Human Regular U-500 Insulin TID | Change From Baseline to Week 24 in HbA1c Based on Baseline TDD Insulin ≤2.0 Units/kg and >2.0 Units/kg | Baseline TDD ≤2.0 units/kg (n=50, 46) | -0.99 percentage of HbA1c | Standard Error 0.14 |
| Human Regular U-500 Insulin TID | Change From Baseline to Week 24 in HbA1c Based on Baseline TDD Insulin ≤2.0 Units/kg and >2.0 Units/kg | Baseline TDD >2.0 units/kg (n=112, 115) | -1.19 percentage of HbA1c | Standard Error 0.1 |
| Human Regular U-500 Insulin BID | Change From Baseline to Week 24 in HbA1c Based on Baseline TDD Insulin ≤2.0 Units/kg and >2.0 Units/kg | Baseline TDD ≤2.0 units/kg (n=50, 46) | -1.32 percentage of HbA1c | Standard Error 0.15 |
| Human Regular U-500 Insulin BID | Change From Baseline to Week 24 in HbA1c Based on Baseline TDD Insulin ≤2.0 Units/kg and >2.0 Units/kg | Baseline TDD >2.0 units/kg (n=112, 115) | -1.18 percentage of HbA1c | Standard Error 0.1 |
Secondary
Change From Baseline to Week 24 in Number of Insulin Injections
The number of insulin injections per day at baseline (Week 0) and at Week 24 are presented.
Time frame: Baseline, Week 24
Population: Randomized participants who received at least 1 dose of U-500R. Last observation carried forward (LOCF) was used to impute missing postbaseline values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Human Regular U-500 Insulin TID | Change From Baseline to Week 24 in Number of Insulin Injections | Baseline | 4.765 injections per day | Standard Deviation 1.234 |
| Human Regular U-500 Insulin TID | Change From Baseline to Week 24 in Number of Insulin Injections | Week 24 | 3.000 injections per day | Standard Deviation 0 |
| Human Regular U-500 Insulin BID | Change From Baseline to Week 24 in Number of Insulin Injections | Baseline | 4.783 injections per day | Standard Deviation 1.307 |
| Human Regular U-500 Insulin BID | Change From Baseline to Week 24 in Number of Insulin Injections | Week 24 | 2.000 injections per day | Standard Deviation 0 |
Secondary
Change From Baseline to Week 24 in Percentage of Participants With Hypoglycemic Events Based on Baseline TDD Insulin ≥2.0 Units/kg and <2.0 Units/kg
Participants were stratified by their baseline TDD insulin (≤2.0 units (U)/kg or \>2.0 U/kg). The percentage of participants at risk of developing hypoglycemia (including documented symptomatic, asymptomatic, probable symptomatic, unspecified, or severe hypoglycemia) is presented at Baseline and at Week 24 and was calculated using MMRM fit with options of the binomial distribution and log link function including treatment, TDD (\>300 units or ≤300 units), pioglitazone use (yes or no), visit, and treatment-by-visit interaction as fixed effects, and baseline HbA1c value as a covariate.
Time frame: Baseline, Week 24
Population: Randomized participants who received at least 1 dose of U-500R.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Human Regular U-500 Insulin TID | Change From Baseline to Week 24 in Percentage of Participants With Hypoglycemic Events Based on Baseline TDD Insulin ≥2.0 Units/kg and <2.0 Units/kg | Baseline TDD≤2.0 U/kg, Baseline risk (n=50, 46) | 56.00 percentage of participants |
| Human Regular U-500 Insulin TID | Change From Baseline to Week 24 in Percentage of Participants With Hypoglycemic Events Based on Baseline TDD Insulin ≥2.0 Units/kg and <2.0 Units/kg | Baseline TDD ≤2.0 U/kg, Week 24 risk (n=50, 46) | 94.00 percentage of participants |
| Human Regular U-500 Insulin TID | Change From Baseline to Week 24 in Percentage of Participants With Hypoglycemic Events Based on Baseline TDD Insulin ≥2.0 Units/kg and <2.0 Units/kg | Baseline TDD >2.0 U/kg, Baseline risk (n=112, 115) | 47.32 percentage of participants |
| Human Regular U-500 Insulin TID | Change From Baseline to Week 24 in Percentage of Participants With Hypoglycemic Events Based on Baseline TDD Insulin ≥2.0 Units/kg and <2.0 Units/kg | Baseline TDD >2.0 U/kg, Week 24 risk (n=112, 115) | 96.43 percentage of participants |
| Human Regular U-500 Insulin BID | Change From Baseline to Week 24 in Percentage of Participants With Hypoglycemic Events Based on Baseline TDD Insulin ≥2.0 Units/kg and <2.0 Units/kg | Baseline TDD >2.0 U/kg, Week 24 risk (n=112, 115) | 97.39 percentage of participants |
| Human Regular U-500 Insulin BID | Change From Baseline to Week 24 in Percentage of Participants With Hypoglycemic Events Based on Baseline TDD Insulin ≥2.0 Units/kg and <2.0 Units/kg | Baseline TDD≤2.0 U/kg, Baseline risk (n=50, 46) | 39.13 percentage of participants |
| Human Regular U-500 Insulin BID | Change From Baseline to Week 24 in Percentage of Participants With Hypoglycemic Events Based on Baseline TDD Insulin ≥2.0 Units/kg and <2.0 Units/kg | Baseline TDD >2.0 U/kg, Baseline risk (n=112, 115) | 51.30 percentage of participants |
| Human Regular U-500 Insulin BID | Change From Baseline to Week 24 in Percentage of Participants With Hypoglycemic Events Based on Baseline TDD Insulin ≥2.0 Units/kg and <2.0 Units/kg | Baseline TDD ≤2.0 U/kg, Week 24 risk (n=50, 46) | 86.96 percentage of participants |
Secondary
Change From Baseline to Week 24 in Total Daily Dose (TDD; Units/kg) of Insulin
Baseline TDD was defined as the last U-100 insulin TDD prior to receiving the first dose of U-500R insulin. LS means of change from baseline were calculated using MMRM with investigator, baseline HbA1c (≤8% or \>8%), treatment (TID or BID), visit, and treatment-by-visit interaction as fixed effects and baseline TDD as a covariate.
Time frame: Baseline, Week 24
Population: Randomized participants who received at least 1 dose of U-500R with evaluable TDD data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Human Regular U-500 Insulin TID | Change From Baseline to Week 24 in Total Daily Dose (TDD; Units/kg) of Insulin | 0.32 units per kilogram (units/kg) | Standard Error 0.08 |
| Human Regular U-500 Insulin BID | Change From Baseline to Week 24 in Total Daily Dose (TDD; Units/kg) of Insulin | 0.32 units per kilogram (units/kg) | Standard Error 0.08 |
Secondary
Change From Baseline to Week 24 in Total Daily Dose (TDD; Units) of Insulin
Baseline TDD was defined as the last U-100 insulin TDD prior to receiving the first dose of U-500R insulin. LS means of change from baseline were calculated using MMRM with investigator, baseline HbA1c (≤8% or \>8%), treatment (TID or BID), visit, and treatment-by-visit interaction as fixed effects and baseline TDD as a covariate.
Time frame: Baseline, Week 24
Population: Randomized participants who received at least 1 dose of U-500R with evaluable TDD data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Human Regular U-500 Insulin TID | Change From Baseline to Week 24 in Total Daily Dose (TDD; Units) of Insulin | 55.19 units | Standard Error 10.16 |
| Human Regular U-500 Insulin BID | Change From Baseline to Week 24 in Total Daily Dose (TDD; Units) of Insulin | 51.39 units | Standard Error 10.24 |
Secondary
Mean Change From Baseline to Week 24 in 7-Point Self-Monitored Blood Glucose (SMBG)
The 7-point SMBG is a participant self-administered blood glucose test which utilizes measurements at specific time points over a 24-hour period, including pre-morning meal (fasting), 2 hours after morning meal, pre-midday meal, 2 hours after midday meal, pre-evening meal, 2 hours after evening meal, and 3 AM. LS means of change from baseline were calculated using MMRM with investigator, baseline HbA1c (≤8% or \>8%), baseline TDD (≤300 or \>300 units), treatment (TID or BID), visit, and treatment-by-visit interaction as fixed effects and baseline SMBG as a covariate.
Time frame: Baseline, Week 24
Population: Randomized participants who received at least 1 dose of U-500R with evaluable SMBG data.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Human Regular U-500 Insulin TID | Mean Change From Baseline to Week 24 in 7-Point Self-Monitored Blood Glucose (SMBG) | Pre-midday Meal (n=150, 149) | -23.54 mg/dL | Standard Error 4.17 |
| Human Regular U-500 Insulin TID | Mean Change From Baseline to Week 24 in 7-Point Self-Monitored Blood Glucose (SMBG) | Pre-evening Meal (n=150, 149) | -34.17 mg/dL | Standard Error 3.93 |
| Human Regular U-500 Insulin TID | Mean Change From Baseline to Week 24 in 7-Point Self-Monitored Blood Glucose (SMBG) | 2 Hours After Morning Meal (n=146, 133) | -21.68 mg/dL | Standard Error 4.29 |
| Human Regular U-500 Insulin TID | Mean Change From Baseline to Week 24 in 7-Point Self-Monitored Blood Glucose (SMBG) | 2 Hours After Evening Meal (n=147, 142) | -40.56 mg/dL | Standard Error 4.13 |
| Human Regular U-500 Insulin TID | Mean Change From Baseline to Week 24 in 7-Point Self-Monitored Blood Glucose (SMBG) | 2 Hours After Midday Meal (n=143, 133) | -24.31 mg/dL | Standard Error 4.5 |
| Human Regular U-500 Insulin TID | Mean Change From Baseline to Week 24 in 7-Point Self-Monitored Blood Glucose (SMBG) | 3 AM (n=147, 140) | -36.77 mg/dL | Standard Error 4.34 |
| Human Regular U-500 Insulin TID | Mean Change From Baseline to Week 24 in 7-Point Self-Monitored Blood Glucose (SMBG) | Pre-morning Meal (n=150, 149) | -24.10 mg/dL | Standard Error 3.96 |
| Human Regular U-500 Insulin BID | Mean Change From Baseline to Week 24 in 7-Point Self-Monitored Blood Glucose (SMBG) | 3 AM (n=147, 140) | -47.82 mg/dL | Standard Error 4.29 |
| Human Regular U-500 Insulin BID | Mean Change From Baseline to Week 24 in 7-Point Self-Monitored Blood Glucose (SMBG) | Pre-morning Meal (n=150, 149) | -29.19 mg/dL | Standard Error 3.91 |
| Human Regular U-500 Insulin BID | Mean Change From Baseline to Week 24 in 7-Point Self-Monitored Blood Glucose (SMBG) | 2 Hours After Morning Meal (n=146, 133) | -31.32 mg/dL | Standard Error 4.29 |
| Human Regular U-500 Insulin BID | Mean Change From Baseline to Week 24 in 7-Point Self-Monitored Blood Glucose (SMBG) | Pre-midday Meal (n=150, 149) | -32.26 mg/dL | Standard Error 4.11 |
| Human Regular U-500 Insulin BID | Mean Change From Baseline to Week 24 in 7-Point Self-Monitored Blood Glucose (SMBG) | 2 Hours After Midday Meal (n=143, 133) | -22.53 mg/dL | Standard Error 4.49 |
| Human Regular U-500 Insulin BID | Mean Change From Baseline to Week 24 in 7-Point Self-Monitored Blood Glucose (SMBG) | Pre-evening Meal (n=150, 149) | -32.96 mg/dL | Standard Error 3.85 |
| Human Regular U-500 Insulin BID | Mean Change From Baseline to Week 24 in 7-Point Self-Monitored Blood Glucose (SMBG) | 2 Hours After Evening Meal (n=147, 142) | -38.36 mg/dL | Standard Error 4.11 |
Secondary
Percentage of Participants Achieving HbA1c of ≤6.5%, <7.0%, <7.5%, and <8.0% at Week 24
The percentage of participants achieving an HbA1c of ≤6.5%, \<7.0%, \<7.5%, and \<8.0% at Week 24 was calculated by the dividing the number of participants meeting the criteria by the total number of participants analyzed, multiplied by 100.
Time frame: Week 24
Population: Randomized participants who received at least 1 dose of U-500R, who were not at the HbA1c target at baseline, and had evaluable HbA1c data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Human Regular U-500 Insulin TID | Percentage of Participants Achieving HbA1c of ≤6.5%, <7.0%, <7.5%, and <8.0% at Week 24 | HbA1c <7.5% (n=148, 143) | 64.19 percentage of participants |
| Human Regular U-500 Insulin TID | Percentage of Participants Achieving HbA1c of ≤6.5%, <7.0%, <7.5%, and <8.0% at Week 24 | HbA1c <8.0% (n=120, 123) | 77.50 percentage of participants |
| Human Regular U-500 Insulin TID | Percentage of Participants Achieving HbA1c of ≤6.5%, <7.0%, <7.5%, and <8.0% at Week 24 | HbA1c <7.0% (n=158, 159) | 42.41 percentage of participants |
| Human Regular U-500 Insulin TID | Percentage of Participants Achieving HbA1c of ≤6.5%, <7.0%, <7.5%, and <8.0% at Week 24 | HbA1c ≤6.5% (n=159, 161) | 20.13 percentage of participants |
| Human Regular U-500 Insulin BID | Percentage of Participants Achieving HbA1c of ≤6.5%, <7.0%, <7.5%, and <8.0% at Week 24 | HbA1c <7.0% (n=158, 159) | 41.51 percentage of participants |
| Human Regular U-500 Insulin BID | Percentage of Participants Achieving HbA1c of ≤6.5%, <7.0%, <7.5%, and <8.0% at Week 24 | HbA1c <7.5% (n=148, 143) | 61.54 percentage of participants |
| Human Regular U-500 Insulin BID | Percentage of Participants Achieving HbA1c of ≤6.5%, <7.0%, <7.5%, and <8.0% at Week 24 | HbA1c <8.0% (n=120, 123) | 77.24 percentage of participants |
| Human Regular U-500 Insulin BID | Percentage of Participants Achieving HbA1c of ≤6.5%, <7.0%, <7.5%, and <8.0% at Week 24 | HbA1c ≤6.5% (n=159, 161) | 23.60 percentage of participants |
Secondary
Percentage of Participants With Hypoglycemic Events
Hypoglycemic events (HE) were classified as severe (an event requiring assistance from another person \[accompanied by neurologic/cognitive impairment\]), documented symptomatic (an event which is associated with signs/symptoms of hypoglycemia and plasma glucose \[PG\] ≤70 milligrams per deciliter \[mg/dL\]), documented symptomatic nocturnal (any documented symptomatic HE that occurred between bedtime and waking), or asymptomatic (any measured PG ≤70 mg/dL not accompanied by hypoglycemic signs/symptoms). The percentage of participants with HE at 24 weeks was calculated by the dividing the number of participants meeting the criteria by the total number of participants analyzed, multiplied by 100. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Time frame: Baseline through Week 24
Population: Randomized participants who received at least 1 dose of U-500R.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Human Regular U-500 Insulin TID | Percentage of Participants With Hypoglycemic Events | Severe HE | 1.85 percentage of participants |
| Human Regular U-500 Insulin TID | Percentage of Participants With Hypoglycemic Events | Documented Symptomatic HE | 91.98 percentage of participants |
| Human Regular U-500 Insulin TID | Percentage of Participants With Hypoglycemic Events | Documented Symptomatic Nocturnal HE | 77.78 percentage of participants |
| Human Regular U-500 Insulin TID | Percentage of Participants With Hypoglycemic Events | Asymptomatic HE | 64.20 percentage of participants |
| Human Regular U-500 Insulin BID | Percentage of Participants With Hypoglycemic Events | Asymptomatic HE | 66.46 percentage of participants |
| Human Regular U-500 Insulin BID | Percentage of Participants With Hypoglycemic Events | Severe HE | 3.73 percentage of participants |
| Human Regular U-500 Insulin BID | Percentage of Participants With Hypoglycemic Events | Documented Symptomatic Nocturnal HE | 80.75 percentage of participants |
| Human Regular U-500 Insulin BID | Percentage of Participants With Hypoglycemic Events | Documented Symptomatic HE | 90.06 percentage of participants |
Secondary
Time to Reach HbA1c Target Values
The cumulative number of participants achieving an HbA1c of ≤6.5%, \<7.0%, \<7.5%, and \<8.0% is summarized at Weeks 6, 12, 18, and 24. The number of participants at risk (n) is also provided for each target value and timepoint.
Time frame: Baseline through 6, 12, 18, and 24 weeks.
Population: Randomized participants who received at least 1 dose of U-500R, who were not at the HbA1c target at baseline, and had evaluable HbA1c data
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Human Regular U-500 Insulin TID | Time to Reach HbA1c Target Values | HbA1c ≤6.5%, Week 6 (n=154, 155) | 1 participants |
| Human Regular U-500 Insulin TID | Time to Reach HbA1c Target Values | HbA1c <7.5%, Week 6 (n=144, 137) | 30 participants |
| Human Regular U-500 Insulin TID | Time to Reach HbA1c Target Values | HbA1c <7.0%, Week 6 (n=154, 153) | 14 participants |
| Human Regular U-500 Insulin TID | Time to Reach HbA1c Target Values | HbA1c <7.5%, Week 12 (n=140, 134) | 59 participants |
| Human Regular U-500 Insulin TID | Time to Reach HbA1c Target Values | HbA1c ≤6.5%, Week 18 (n=140, 145) | 24 participants |
| Human Regular U-500 Insulin TID | Time to Reach HbA1c Target Values | HbA1c <7.5%, Week 18 (n=136, 132) | 81 participants |
| Human Regular U-500 Insulin TID | Time to Reach HbA1c Target Values | HbA1c <7.0%, Week 12 (n=148, 149) | 31 participants |
| Human Regular U-500 Insulin TID | Time to Reach HbA1c Target Values | HbA1c ≤6.5%, Week 12 (n=145, 151) | 15 participants |
| Human Regular U-500 Insulin TID | Time to Reach HbA1c Target Values | HbA1c <8.0%, Week 6 (n=117, 117) | 32 participants |
| Human Regular U-500 Insulin TID | Time to Reach HbA1c Target Values | HbA1c <7.0%, Week 18 (n=144, 145) | 52 participants |
| Human Regular U-500 Insulin TID | Time to Reach HbA1c Target Values | HbA1c <8.0%, Week 12 (n=114, 115) | 66 participants |
| Human Regular U-500 Insulin TID | Time to Reach HbA1c Target Values | HbA1c ≤6.5%, Week 24 (n=76, 65) | 28 participants |
| Human Regular U-500 Insulin TID | Time to Reach HbA1c Target Values | HbA1c <8.0%, Week 18 (n=111, 113) | 85 participants |
| Human Regular U-500 Insulin TID | Time to Reach HbA1c Target Values | HbA1c <7.0%, Week 24 (n=53, 52) | 60 participants |
| Human Regular U-500 Insulin TID | Time to Reach HbA1c Target Values | HbA1c <8.0%, Week 24 (n=20, 19) | 89 participants |
| Human Regular U-500 Insulin TID | Time to Reach HbA1c Target Values | HbA1c <7.5%, Week 24 (n=34, 31) | 90 participants |
| Human Regular U-500 Insulin BID | Time to Reach HbA1c Target Values | HbA1c <8.0%, Week 24 (n=20, 19) | 95 participants |
| Human Regular U-500 Insulin BID | Time to Reach HbA1c Target Values | HbA1c ≤6.5%, Week 6 (n=154, 155) | 6 participants |
| Human Regular U-500 Insulin BID | Time to Reach HbA1c Target Values | HbA1c ≤6.5%, Week 12 (n=145, 151) | 15 participants |
| Human Regular U-500 Insulin BID | Time to Reach HbA1c Target Values | HbA1c ≤6.5%, Week 18 (n=140, 145) | 27 participants |
| Human Regular U-500 Insulin BID | Time to Reach HbA1c Target Values | HbA1c ≤6.5%, Week 24 (n=76, 65) | 37 participants |
| Human Regular U-500 Insulin BID | Time to Reach HbA1c Target Values | HbA1c <7.0%, Week 6 (n=154, 153) | 10 participants |
| Human Regular U-500 Insulin BID | Time to Reach HbA1c Target Values | HbA1c <7.0%, Week 12 (n=148, 149) | 36 participants |
| Human Regular U-500 Insulin BID | Time to Reach HbA1c Target Values | HbA1c <7.0%, Week 18 (n=144, 145) | 55 participants |
| Human Regular U-500 Insulin BID | Time to Reach HbA1c Target Values | HbA1c <7.0%, Week 24 (n=53, 52) | 65 participants |
| Human Regular U-500 Insulin BID | Time to Reach HbA1c Target Values | HbA1c <7.5%, Week 6 (n=144, 137) | 20 participants |
| Human Regular U-500 Insulin BID | Time to Reach HbA1c Target Values | HbA1c <7.5%, Week 12 (n=140, 134) | 59 participants |
| Human Regular U-500 Insulin BID | Time to Reach HbA1c Target Values | HbA1c <7.5%, Week 18 (n=136, 132) | 78 participants |
| Human Regular U-500 Insulin BID | Time to Reach HbA1c Target Values | HbA1c <7.5%, Week 24 (n=34, 31) | 87 participants |
| Human Regular U-500 Insulin BID | Time to Reach HbA1c Target Values | HbA1c <8.0%, Week 6 (n=117, 117) | 34 participants |
| Human Regular U-500 Insulin BID | Time to Reach HbA1c Target Values | HbA1c <8.0%, Week 12 (n=114, 115) | 72 participants |
| Human Regular U-500 Insulin BID | Time to Reach HbA1c Target Values | HbA1c <8.0%, Week 18 (n=111, 113) | 86 participants |