Type 2 Diabetes, Type 2 Diabetes Treated With Insulin
Conditions
Brief summary
The reason for this study is to evaluate if the once-weekly study drug insulin efsitora alfa (LY3209590) is safe and effective compared with daily insulin glargine in participants with Type 2 diabetes (T2D) that have already been treated with basal insulin and at least 2 injections per day of prandial insulin. The study consists of a 3-week screening/lead-in period, a 26-week treatment period and a 5-week safety follow-up period. The study will last up to 34 weeks.
Interventions
Administered SC
Administered SC
Administered SC
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 No maximum
Healthy volunteers
No
Inclusion criteria
* Have a diagnosis of T2D according to the world health organization (WHO) criteria, currently treated with basal insulin and at least 2 injections of prandial insulin per day. * Are receiving ≥10 units of total basal insulin per day at screening. * Are receiving ≤2 units/kilogram/day of total daily insulin at screening * Have an HbA1c value of 7.0% to 10%, inclusive, as determined by the central laboratory at screening * Have been treated with a stable regimen of one of the following basal insulins used according to local product label with or without noninsulin diabetes therapy for at least 90 days prior to screening * once daily U-100 or U-200 insulin degludec * once daily U-100 or U-300 insulin glargine * once or twice daily U-100 insulin detemir or * once or twice daily human insulin Neutral Protamine Hagedorn * Have been treated with at least twice daily dosing of one of the following insulins used according to local product label for at least 90 days prior to screening. One dose of prandial insulin must occur at the evening meal. * Insulin lispro-aabc * Insulin lispro (U-100 and U-200)s, IN\], U-100 or U200) * Insulin aspart (U-100) * Insulin glulisine (U-100), or * Regular insulin (U-100) * Acceptable noninsulin diabetes therapies may include 0 to up to 3 of the following with a stable dose for at least 90 days prior to screening * dipeptidyl peptidase IV inhibitors * sodium-glucose co-transporter-2 inhibitors * biguanides (for example, metformin), or * glucagon-like peptide-1 receptor agonists Note: All noninsulin diabetes therapies must be used in accordance with the corresponding local product label at the time of screening, and participants should be willing to continue stable dosing throughout the study * Have a body mass index ≤45 kilogram/square meter (kg/m²)
Exclusion criteria
* Have a diagnosis of type 1 diabetes mellitus or latent autoimmune diabetes, or specific type of diabetes other than T2D (for example, monogenic diabetes, diseases of the exocrine pancreas, drug-induced or chemical-induced diabetes). * Are currently receiving any of the following insulin therapies anytime in the past 90 days: * insulin mixtures * insulin human, inhalation powder, or * continuous subcutaneous insulin infusion therapy, or * regular insulin U-500 * Have a history of greater than 1 episode of ketoacidosis or hyperosmolar state/coma requiring hospitalization in the 6 months prior to screening * Have had any episodes of severe hypoglycemia, defined as requiring assistance due to neurologically disabling hypoglycemia, within the 6 months prior to screening * Have hypoglycemia unawareness in the opinion of the investigator * Anticipate making changes in personal CGM or flash glucose monitoring (FGM) use (for example, initiation, stopping, or changing device) during the study. * Have had New York Heart Association Class IV heart failure or any of the following cardiovascular conditions in the past 3 months prior to screening: acute myocardial infarction, cerebrovascular accident (stroke), or coronary bypass surgery. * Have undergone gastric bypass (bariatric) surgery, restrictive bariatric surgery, or sleeve gastrectomy within 1 year prior to screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Hemoglobin A1c (HbA1c) [Noninferiority] | Baseline, Week 26 | HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving HbA1c <7% Without Nocturnal Hypoglycemia | Week 26 | Percentage of participants achieving HbA1c \<7% without nocturnal hypoglycemia \[\<54 milligram/deciliter (mg/dL) 3.0 millimole/Liter (mmol/L)\] or severe during treatment phase up to week 26. Nocturnal hypoglycemia is a hypoglycemia event, including severe hypoglycemia, that occurs at night and presumably during sleep between midnight and 6:00 am. |
| Nocturnal Hypoglycemia Event Rate | Baseline Up To Week 26 | The event rate of participant-reported clinically significant nocturnal hypoglycemia, (where glucose \<54 mg/dL (3.0 mmol/L) or severe and occurs at night and presumably during sleep between midnight and 6:00 AM), measured during treatment phase up to week 26. Group mean is reported here. |
| Change From Baseline in Fasting Glucose | Baseline, Week 26 | Change from baseline in fasting glucose measured by self-monitoring blood glucose (SMBG). |
| Percentage of Time in Glucose Range | Week 22 to Week 26 | Percentage of Time in glucose range between 70 and 180 mg/dL (3.9 and 10.0 mmol/L), inclusive measured during the continuous glucose monitoring (CGM) session. |
| Percentage of Time in Hypoglycemia Range | Week 22 to Week 26 | Percentage of Time in hypoglycemia range with glucose \<54 mg/dL (3.0 mmol/L), measured by CGM. |
| Percentage of Time in Hyperglycemia Range | Week 22 to Week 26 | Percentage of Time in hyperglycemia range with glucose \>180 mg/dL (10.0 mmol/L), measured by CGM. |
| Glucose Variability Between Weeks 22 to 26 | Week 22 to Week 26 | Glucose variability measured as coefficient of variation for glucose within day for 24-hour period between Week 22 and 26 was reported. |
| Change From Baseline in HbA1c [Superiority] | Baseline, Week 26 | HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time. |
| Bolus Insulin Dose at Week 26 | Week 26 | Average daily bolus Insulin Dose at Week 26 was reported. |
| Total Insulin Dose at Week 26 | Week 26 | Average total weekly insulin dose at Week 26 was reported. |
| Basal Insulin Dose to Total Insulin Dose Ratio at Week 26 | Week 26 | Basal insulin dose to total insulin dose ratio at Week 26 was reported. |
| Hypoglycemia Event Rate | Baseline up to Week 26 | Hypoglycemia event rate was reported. Hypoglycemia with glucose \<54 mg/dL (Level 2) or Severe Hypoglycemia (Level 3) was reported. A severe hypoglycemic event is characterized by altered mental or physical status requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions for the treatment of hypoglycemia. Group mean was reported here. |
| Change From Baseline in Body Weight | Baseline, Week 26 | Change from baseline in body weight was reported. |
| Treatment Experience for Diabetes Injection Device at Week 26 - Experience Questionnaire (DID-EQ) | Week 26 | The DID-EQ is a self-administered, 10-item questionnaire designed to assess participants' perceptions of diabetes injection delivery systems for diabetes. The Device Characteristic Subscale is comprised of items 1 to 7 which focus on specific characteristics of injection devices. Each item is rated on a four-point Likert scale. Scores are transformed and range from 0 to 100. Higher scores indicate more positive perceptions of injection device characteristics |
| Basal Insulin Dose at Week 26 | Week 26 | Average weekly basal Insulin Dose at Week 26 was reported. |
Countries
Argentina, Germany, India, Italy, Mexico, Puerto Rico, Spain, United States
Participant flow
Recruitment details
Participants underwent a 26-week treatment period, followed by a 5-week safety follow-up period.
Participants by arm
| Arm | Count |
|---|---|
| 500 U/mL - Insulin Efsitora Participants received 500 U/mL insulin efsitora administered SC QW along with 100 U/mL insulin lispro given SC. | 365 |
| 100 U/mL - Insulin Glargine Participants received 100 U/mL insulin glargine administered SC QD along with 100 U/mL insulin lispro given SC. | 365 |
| Total | 730 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Follow-Up Period | Adverse Event | 1 | 0 |
| Follow-Up Period | Death | 1 | 0 |
| Follow-Up Period | Lost to Follow-up | 3 | 1 |
| Follow-Up Period | Withdrawal by Subject | 0 | 4 |
| Treatment Period | Adverse Event | 3 | 0 |
| Treatment Period | Assigned Treatment by Mistake | 4 | 3 |
| Treatment Period | Death | 0 | 1 |
| Treatment Period | Lost to Follow-up | 2 | 1 |
| Treatment Period | Non-Compliance with Study Drug | 1 | 3 |
| Treatment Period | Physician Decision | 2 | 0 |
| Treatment Period | Protocol Violation | 0 | 1 |
| Treatment Period | Withdrawal by Subject | 5 | 12 |
Baseline characteristics
| Characteristic | Total | 100 U/mL - Insulin Glargine | 500 U/mL - Insulin Efsitora |
|---|---|---|---|
| Age, Continuous | 58.9 years STANDARD_DEVIATION 10.5 | 59.4 years STANDARD_DEVIATION 10.5 | 58.3 years STANDARD_DEVIATION 10.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 404 Participants | 203 Participants | 201 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 324 Participants | 161 Participants | 163 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 1 Participants | 1 Participants |
| HemoglobinA1c (HbA1c) | 8.18 Percentage of HbA1c STANDARD_DEVIATION 0.81 | 8.18 Percentage of HbA1c STANDARD_DEVIATION 0.79 | 8.17 Percentage of HbA1c STANDARD_DEVIATION 0.83 |
| Race (NIH/OMB) American Indian or Alaska Native | 91 Participants | 45 Participants | 46 Participants |
| Race (NIH/OMB) Asian | 105 Participants | 51 Participants | 54 Participants |
| Race (NIH/OMB) Black or African American | 31 Participants | 11 Participants | 20 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 503 Participants | 258 Participants | 245 Participants |
| Region of Enrollment Argentina | 166 Participants | 83 Participants | 83 Participants |
| Region of Enrollment Germany | 51 Participants | 24 Participants | 27 Participants |
| Region of Enrollment India | 100 Participants | 50 Participants | 50 Participants |
| Region of Enrollment Italy | 26 Participants | 15 Participants | 11 Participants |
| Region of Enrollment Mexico | 169 Participants | 84 Participants | 85 Participants |
| Region of Enrollment Spain | 70 Participants | 35 Participants | 35 Participants |
| Region of Enrollment United States | 148 Participants | 74 Participants | 74 Participants |
| Sex: Female, Male Female | 369 Participants | 176 Participants | 193 Participants |
| Sex: Female, Male Male | 361 Participants | 189 Participants | 172 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 365 | 1 / 365 |
| other Total, other adverse events | 35 / 365 | 40 / 365 |
| serious Total, serious adverse events | 25 / 365 | 24 / 365 |
Outcome results
Primary
Change From Baseline in Hemoglobin A1c (HbA1c) [Noninferiority]
HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time.
Time frame: Baseline, Week 26
Population: All participants who received at least one dose of study drug and had at least one post-baseline HbA1c data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 500 U/mL - Insulin Efsitora | Change From Baseline in Hemoglobin A1c (HbA1c) [Noninferiority] | -1.01 Percentage of HbA1c | Standard Error 0.0463 |
| 100 U/mL - Insulin Glargine | Change From Baseline in Hemoglobin A1c (HbA1c) [Noninferiority] | -1.00 Percentage of HbA1c | Standard Error 0.0463 |
Comparison: Least Squares (LS) Mean was determined using ANCOVA model with Baseline + Country + Personal Use of CGM or FGM at Randomization + Treatment (Type III sum of squares) as variables. Missing data at Week 26 were imputed by return-to-baseline multiple imputations approach. A total of 100 datasets were imputed.95% CI: [-0.14, 0.116]
Secondary
Basal Insulin Dose at Week 26
Average weekly basal Insulin Dose at Week 26 was reported.
Time frame: Week 26
Population: All participants who received at least one dose of study drug and had evaluable data for this outcome.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 500 U/mL - Insulin Efsitora | Basal Insulin Dose at Week 26 | 391.59 Units per week of basal insulin | Standard Error 7.482 |
| 100 U/mL - Insulin Glargine | Basal Insulin Dose at Week 26 | 426.62 Units per week of basal insulin | Standard Error 7.323 |
Comparison: LS Mean was determined by Mixed Model Repeated Measures (MMRM) model using BASELINE + Hemoglobin A1c Stratum at Baseline + Country + Personal Use CGM or FGM at Randomization + Treatment + Time + Treatment\*Time (Type III sum of squares) as variables. Variance-covariance structure was set as compound symmetry.p-value: <0.00195% CI: [-55.57, -14.5]Mixed Models Analysis
Secondary
Basal Insulin Dose to Total Insulin Dose Ratio at Week 26
Basal insulin dose to total insulin dose ratio at Week 26 was reported.
Time frame: Week 26
Population: All participants who received at least one dose of the study drug and had evaluable data for this outcome.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 500 U/mL - Insulin Efsitora | Basal Insulin Dose to Total Insulin Dose Ratio at Week 26 | 70.09 Ratio | Standard Error 0.749 |
| 100 U/mL - Insulin Glargine | Basal Insulin Dose to Total Insulin Dose Ratio at Week 26 | 66.55 Ratio | Standard Error 0.722 |
Comparison: LS Mean was determined by MMRM model using BASELINE + Hemoglobin A1c Stratum at Baseline + Country + Personal Use CGM or FGM at Randomization + Treatment + Time + Treatment\*Time (Type III sum of squares) as variables. Variance-covariance structure was set as compound symmetry.p-value: <0.00195% CI: [1.49, 5.58]Mixed Models Analysis
Secondary
Bolus Insulin Dose at Week 26
Average daily bolus Insulin Dose at Week 26 was reported.
Time frame: Week 26
Population: All participants who received at least one dose of the study drug and had evaluable data for this outcome.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 500 U/mL - Insulin Efsitora | Bolus Insulin Dose at Week 26 | 27.01 Units per day of bolus insulin | Standard Error 1.182 |
| 100 U/mL - Insulin Glargine | Bolus Insulin Dose at Week 26 | 34.56 Units per day of bolus insulin | Standard Error 1.156 |
Comparison: LS Mean was determined by MMRM model using BASELINE + Hemoglobin A1c Stratum at Baseline + Country + Personal Use CGM or FGM at Randomization + Treatment + Time + Treatment\*Time (Type III sum of squares) as variables. Variance-covariance structure was set as compound symmetry.p-value: <0.00195% CI: [-10.79, -4.3]Mixed Models Analysis
Secondary
Change From Baseline in Body Weight
Change from baseline in body weight was reported.
Time frame: Baseline, Week 26
Population: All participants who received at least one dose of study drug and had evaluable data for this outcome.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 500 U/mL - Insulin Efsitora | Change From Baseline in Body Weight | 2.67 kilograms (kg) | Standard Error 0.165 |
| 100 U/mL - Insulin Glargine | Change From Baseline in Body Weight | 2.53 kilograms (kg) | Standard Error 0.165 |
Comparison: LS Mean was determined by MMRM model using BASELINE + Treatment + Time + Treatment\*Time (Type III sum of squares) as variables.p-value: 0.54395% CI: [-0.32, 0.6]Mixed Models Analysis
Secondary
Change From Baseline in Fasting Glucose
Change from baseline in fasting glucose measured by self-monitoring blood glucose (SMBG).
Time frame: Baseline, Week 26
Population: All participants who received at least one dose of study drug and had evaluable data for this outcome.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 500 U/mL - Insulin Efsitora | Change From Baseline in Fasting Glucose | -30.87 milligrams per deciliter (mg/dL) | Standard Error 1.876 |
| 100 U/mL - Insulin Glargine | Change From Baseline in Fasting Glucose | -26.58 milligrams per deciliter (mg/dL) | Standard Error 1.871 |
Comparison: LS Mean was determined using ANCOVA model using Baseline + Country + Personal Use of CGM or FGM at Randomization + Hemoglobin A1c Stratum at Baseline + Treatment (Type III sum of squares) as variables. Missing data at Baseline were imputed with multiple imputation with assumption of missing at random. Missing data at Week 26 were imputed by return-to-baseline multiple imputations approach. A total of 100 datasets were imputed with one for each of the 100 datasets imputed at Baseline.p-value: 0.10495% CI: [-9.461, 0.886]ANCOVA
Secondary
Change From Baseline in HbA1c [Superiority]
HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time.
Time frame: Baseline, Week 26
Population: All participants who received at least one dose of study drug and had at least one post-baseline HbA1c data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 500 U/mL - Insulin Efsitora | Change From Baseline in HbA1c [Superiority] | -1.01 Percentage of HbA1c | Standard Error 0.0463 |
| 100 U/mL - Insulin Glargine | Change From Baseline in HbA1c [Superiority] | -1.00 Percentage of HbA1c | Standard Error 0.0463 |
Comparison: Least Squares (LS) Mean was determined using ANCOVA model with Baseline + Country + Personal Use of CGM or FGM at Randomization + Treatment (Type III sum of squares) as variables. Missing data at Week 26 were imputed by return-to-baseline multiple imputations approach. A total of 100 datasets were imputed.p-value: 0.85595% CI: [-0.14, 0.116]ANCOVA
Secondary
Glucose Variability Between Weeks 22 to 26
Glucose variability measured as coefficient of variation for glucose within day for 24-hour period between Week 22 and 26 was reported.
Time frame: Week 22 to Week 26
Population: All participants who received at least one dose of study drug and had evaluable data for this outcome.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 500 U/mL - Insulin Efsitora | Glucose Variability Between Weeks 22 to 26 | 28.51 Coefficient of Variation | Standard Error 0.259 |
| 100 U/mL - Insulin Glargine | Glucose Variability Between Weeks 22 to 26 | 28.28 Coefficient of Variation | Standard Error 0.254 |
Comparison: LS Mean was determined by MMRM model with BASELINE + Hemoglobin A1c Stratum at Baseline + Country + Personal Use CGM or FGM at Randomization + Treatment + Time + Treatment\*Time (Type III sum of squares) as variables. Unstructured variance-covariance structure was used.p-value: 0.52395% CI: [-0.48, 0.95]Mixed Models Analysis
Secondary
Hypoglycemia Event Rate
Hypoglycemia event rate was reported. Hypoglycemia with glucose \<54 mg/dL (Level 2) or Severe Hypoglycemia (Level 3) was reported. A severe hypoglycemic event is characterized by altered mental or physical status requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions for the treatment of hypoglycemia. Group mean was reported here.
Time frame: Baseline up to Week 26
Population: All participants who received at least one dose of study drug and had evaluable data for this outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 500 U/mL - Insulin Efsitora | Hypoglycemia Event Rate | 6.58 Events per year | Standard Error 0.709 |
| 100 U/mL - Insulin Glargine | Hypoglycemia Event Rate | 5.94 Events per year | Standard Error 0.618 |
Comparison: Group mean was reported and determined by Negative binomial method using Baseline hypoglycemia rate + Hemoglobin A1c at Baseline (%) + Treatment, with log (exposure in days/365.25) as variables.p-value: 0.44295% CI: [0.85, 1.44]Negative binomial model
Secondary
Nocturnal Hypoglycemia Event Rate
The event rate of participant-reported clinically significant nocturnal hypoglycemia, (where glucose \<54 mg/dL (3.0 mmol/L) or severe and occurs at night and presumably during sleep between midnight and 6:00 AM), measured during treatment phase up to week 26. Group mean is reported here.
Time frame: Baseline Up To Week 26
Population: All participants who received at least one dose of study drug and had evaluable data for this outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 500 U/mL - Insulin Efsitora | Nocturnal Hypoglycemia Event Rate | 0.67 Events per year | Standard Error 0.112 |
| 100 U/mL - Insulin Glargine | Nocturnal Hypoglycemia Event Rate | 1.00 Events per year | Standard Error 0.151 |
Comparison: Group mean is determined by Negative Binomial Model using Number of episodes = Baseline hypoglycemia rate + Hemoglobin A1c at Baseline (%) + Treatment, with log (exposure in days/365.25) as an offset variable.p-value: 0.05895% CI: [0.44, 1.01]Negative binomial model
Secondary
Percentage of Participants Achieving HbA1c <7% Without Nocturnal Hypoglycemia
Percentage of participants achieving HbA1c \<7% without nocturnal hypoglycemia \[\<54 milligram/deciliter (mg/dL) 3.0 millimole/Liter (mmol/L)\] or severe during treatment phase up to week 26. Nocturnal hypoglycemia is a hypoglycemia event, including severe hypoglycemia, that occurs at night and presumably during sleep between midnight and 6:00 am.
Time frame: Week 26
Population: All participants who received at least one dose of study drug and had evaluable data for this outcome.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 500 U/mL - Insulin Efsitora | Percentage of Participants Achieving HbA1c <7% Without Nocturnal Hypoglycemia | 38.6 Percentage of participants |
| 100 U/mL - Insulin Glargine | Percentage of Participants Achieving HbA1c <7% Without Nocturnal Hypoglycemia | 35.9 Percentage of participants |
p-value: 0.50495% CI: [0.81, 1.52]Chi-squared
Secondary
Percentage of Time in Glucose Range
Percentage of Time in glucose range between 70 and 180 mg/dL (3.9 and 10.0 mmol/L), inclusive measured during the continuous glucose monitoring (CGM) session.
Time frame: Week 22 to Week 26
Population: All participants who received at least one dose of the study drug and had evaluable data for this outcome.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 500 U/mL - Insulin Efsitora | Percentage of Time in Glucose Range | 58.39 Percentage of time | Standard Error 0.993 |
| 100 U/mL - Insulin Glargine | Percentage of Time in Glucose Range | 57.05 Percentage of time | Standard Error 0.99 |
Comparison: LS Mean was determined using ANCOVA model using Baseline + Country + Personal Use of CGM or FGM at Randomization + Hemoglobin A1c Stratum at Baseline + Treatment (Type III sum of squares) as variables. Missing data at Baseline were imputed with multiple imputation with assumption of missing at random. Missing data at Week 22-Week 26 were imputed by return-to-baseline multiple imputations approach. A total of 100 datasets were imputed with one for each of the 100 datasets imputed at Baseline.p-value: 0.33795% CI: [-1.404, 4.101]ANCOVA
Secondary
Percentage of Time in Hyperglycemia Range
Percentage of Time in hyperglycemia range with glucose \>180 mg/dL (10.0 mmol/L), measured by CGM.
Time frame: Week 22 to Week 26
Population: All participants who received at least one dose of the study drug and had evaluable data for this outcome.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 500 U/mL - Insulin Efsitora | Percentage of Time in Hyperglycemia Range | 40.10 Percentage of time | Standard Error 1.024 |
| 100 U/mL - Insulin Glargine | Percentage of Time in Hyperglycemia Range | 41.60 Percentage of time | Standard Error 1.024 |
Comparison: LS Mean was determined by ANCOVA model using Baseline + Country + Personal Use of CGM or FGM at Randomization + Hemoglobin A1c Stratum at Baseline + Treatment (Type III sum of squares). Missing data at Baseline were imputed with multiple imputation with assumption of missing at random. Missing data at Week 22-Week 26 were imputed by return-to-baseline multiple imputations approach. A total of 100 datasets were imputed with one for each of the 100 datasets imputed at Baseline.p-value: 0.30495% CI: [-4.358, 1.36]ANCOVA
Secondary
Percentage of Time in Hypoglycemia Range
Percentage of Time in hypoglycemia range with glucose \<54 mg/dL (3.0 mmol/L), measured by CGM.
Time frame: Week 22 to Week 26
Population: All participants who received at least one dose of study drug and had evaluable data for this outcome.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 500 U/mL - Insulin Efsitora | Percentage of Time in Hypoglycemia Range | 6.84 Percentage of time | Standard Error 0.7 |
| 100 U/mL - Insulin Glargine | Percentage of Time in Hypoglycemia Range | 5.25 Percentage of time | Standard Error 0.68 |
Comparison: LS Mean was determined by ANCOVA model using Baseline + Country + Personal Use of CGM or FGM at Randomization + Hemoglobin A1c Stratum at Baseline + Treatment (Type III sum of squares) as variables. Missing data at Baseline were imputed with multiple imputation with assumption of missing at random. Missing data at Week 22-Week 26 were imputed by return-to-baseline multiple imputations approach. A total of 100 datasets were imputed with one for each of the 100 datasets imputed at Baseline.p-value: 0.10495% CI: [-0.327, 3.508]ANCOVA
Secondary
Total Insulin Dose at Week 26
Average total weekly insulin dose at Week 26 was reported.
Time frame: Week 26
Population: All participants who received at least one dose of study drug and had evaluable data for this outcome.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 500 U/mL - Insulin Efsitora | Total Insulin Dose at Week 26 | 592.92 Units per week of insulin | Standard Error 12.56 |
| 100 U/mL - Insulin Glargine | Total Insulin Dose at Week 26 | 666.43 Units per week of insulin | Standard Error 12.144 |
Comparison: LS Mean was determined by MMRM model using BASELINE + Hemoglobin A1c Stratum at Baseline + Country + Personal Use CGM or FGM at Randomization + Treatment + Time + Treatment\*Time (Type III sum of squares) as variables. Variance-covariance structure was set as compound symmetry.p-value: <0.00195% CI: [-107.81, -39.2]Mixed Models Analysis
Secondary
Treatment Experience for Diabetes Injection Device at Week 26 - Experience Questionnaire (DID-EQ)
The DID-EQ is a self-administered, 10-item questionnaire designed to assess participants' perceptions of diabetes injection delivery systems for diabetes. The Device Characteristic Subscale is comprised of items 1 to 7 which focus on specific characteristics of injection devices. Each item is rated on a four-point Likert scale. Scores are transformed and range from 0 to 100. Higher scores indicate more positive perceptions of injection device characteristics
Time frame: Week 26
Population: All participants who received at least one dose of study drug and had evaluable data for this outcome.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 500 U/mL - Insulin Efsitora | Treatment Experience for Diabetes Injection Device at Week 26 - Experience Questionnaire (DID-EQ) | 88.1 Score on a scale | Standard Error 0.77 |
| 100 U/mL - Insulin Glargine | Treatment Experience for Diabetes Injection Device at Week 26 - Experience Questionnaire (DID-EQ) | 86.3 Score on a scale | Standard Error 0.75 |
Comparison: LS Mean was determined by ANCOVA model using Country + Personal Use CGM or FGM at Randomization + Hemoglobin A1c Stratum at Baseline + Treatment (Type III sum of squares) as variables.p-value: 0.09995% CI: [-0.3, 4]ANCOVA