Type 2 Diabetes
Conditions
Brief summary
The reason for this study is to see if the study drug insulin efsitora alfa (LY3209590) is safe and effective in participants with Type 2 diabetes that have already been treated with basal insulin. The study consists of a 3-week screening/lead-in period, a 78-week treatment period and a 5-week safety follow-up period. The study will last up to 86 weeks.
Interventions
Administered SC
DRUGInsulin Degludec
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 been diagnosed with Type 2 diabetes according to the World Health Organization (WHO) criteria treated with basal insulin * Are receiving ≥10 units of basal insulin per day and ≤110 units per day at screening * Have HbA1c value of 6.5% - 10% inclusive, at screening * Have a Body mass index (BMI) less than or equal to 45 kilogram/square meter (kg/m²) * Have been treated with one of the following stable insulin regimens at least 90 days prior to screening: * once daily U100 or U200 of insulin degludec * once daily U100 or U300 of insulin glargine * once or twice daily U100 of insulin detemir, or * once or twice daily human insulin NPH * acceptable non insulin glucose lowering therapies may include 0 to up to 3 of the following: * dipeptidyl peptidase (DPP-4) IV inhibitors * SGLT2 inhibitors * metformin * alphaglucosidase inhibitors or, * Glucagon-Like Peptide-1 (GLP-1) receptor agonists * Participants must be willing to stay on stable dose throughout the study
Exclusion criteria
* Have Type 1 diabetes mellitus * Have acute or chronic hepatitis, cirrhosis, or obvious clinical signs or symptoms of any other liver disease, except Nonalcoholic Fatty Liver Disease (NAFLD) * Estimated glomerular filtration rate (eGFR) \<20 milliliters/minute/1.73 square meter (m²) * Have active or untreated malignancy * Are pregnant * Have a significant weight gain or loss the past 3 months * Have received anytime in the past 6 months, any of the following insulin therapies: * prandial insulin * insulin mixtures * inhaled insulin * U-500 insulin, or * continuous subcutaneous insulin infusion therapy * Have had any of New York Heart Association Class IV heart failure or any of the following CV conditions in the past 3 months: * acute myocardial infarctions * cerebrovascular accident (stroke), or * coronary bypass surgery * Gastrointestinal: have undergone gastric bypass (bariatric) surgery, restrictive bariatric surgery (Lap-Band) 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. Least Squares (LS) Mean was determined using ANCOVA model with Baseline + Country + Type of Basal Insulin used at Baseline + Treatment (Type III sum of squares) as variables. Missing data at Week 26 were imputed by return-to-baseline multiple imputation approach. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Nocturnal Hypoglycemia Event Rate | Baseline up to Week 78 | The event rate of participant-reported clinically significant glucose \<54 mg/dL (3.0 mmol/L) or severe nocturnal hypoglycemia that occurs at night and presumably during sleep between midnight and 6:00 AM), measured during treatment period up to week 78. Group mean is reported here. Group mean is determined by Negative Binomial Model using Number of episodes = Hemoglobin A1c at Baseline (%) + Treatment, with log (exposure in days/365.25) as an offset variable. |
| Percentage of Time in Glucose Range Between 70 and 180 mg/dL (3.9 and 10.0 mmol/L) | Week 22 to Week 26 | Percentage of time in glucose range between 70 and 180 mg/dL (3.9 and 10.0 millimoles per liter (mmol/L)) inclusive measured by continued glucose monitoring (CGM) during CGM session prior to week 26. LS Mean was calculated using ANCOVA model with Baseline + Country + Hemoglobin A1c Stratum at Baseline + Type of Basal Insulin used at Baseline + Treatment (Type III sum of squares) as variables. Missing data during CGM session prior to Week 26 were imputed by return-to-baseline multiple imputation approach. |
| Change From Baseline in Fasting Glucose | Baseline, Week 26 | Fasting glucose measured by Self-Monitoring of Blood Glucose (SMBG). LS Mean was determined using ANCOVA model with Baseline + Country + Type of Basal Insulin at Baseline + Baseline HbA1C Stratum (%) + Treatment (Type III sum of squares) as variables. Missing data at baseline are imputed with multiple imputation under assumption of missing at random. Missing data at Week 26 are imputed by return-to-baseline multiple imputation approach. |
| Weekly Insulin Dose at Week 26 | Week 26 | The average weekly insulin dose at Week 26 was reported. LS Mean was determined by mixed model repeated measures (MMRM) model using BASELINE + Country + Type of Basal Insulin at Baseline + Baseline HbA1C Stratum (%) + Treatment + Time + Treatment\*Time (Type III sum of squares) as variables. Variance-covariance structure was set as compound symmetry. |
| Hypoglycemia Event Rate | Baseline up to Week 78 | Patient reported events of hypoglycemia - 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 and determined by Negative binomial method using Hemoglobin A1c at Baseline (%) + Treatment, with log (exposure in days/365.25) as variables. |
| Change From Baseline in Body Weight | Baseline, Week 78 | Change from baseline in body weight was reported. LS Mean was determined by MMRM model using BASELINE + Treatment + Time + Treatment\*Time (Type III sum of squares) as variables. |
| Change From Baseline in Hemoglobin A1c (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. Least Squares (LS) Mean was determined using ANCOVA model with Baseline + Country + Type of Basal Insulin used at Baseline + Treatment (Type III sum of squares) as variables. Missing data at Week 26 were imputed by return-to-baseline multiple imputation approach. |
| 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 during the CGM session from 22-26 weeks. LS Mean was determined using ANCOVA model using Baseline + Country + Hemoglobin A1c Stratum at Baseline + Type of Basal Insulin used at Baseline + Treatment (Type III sum of squares) as variables. Missing data at baseline were imputed with multiple imputation under assumption of missing at random. Missing data at Week 22-26 were imputed by return-to-baseline multiple imputation approach. |
| Change From Baseline in Treatment-Related Impact Measure - Diabetes (TRIM-D) | Baseline, Week 26, Week 52, Week 78 | The TRIM-D is a self-administered instrument, which assesses the impact of diabetes treatment on participants' functioning and well-being across available diabetes treatments. The TRIM-D consists of 28 items each assessed on a 5-point scale. TRIM-D items assess 5 domains of impact: * Treatment Burden (6 items) * Daily Life (5 items) * Diabetes Management (5 items) * Compliance (4 items), and * Psychological Health (8 items) Items within each domain are summed to obtain a raw domain score, which is then transformed to a 0-100 scale, where higher scores indicate a greater impact on participant's functioning and well-being. LS mean was determined using MMRM model with BASELINE + Country + Type of Basal Insulin at Baseline + Baseline HbA1C Stratum (%) + Treatment + Time + Treatment\*Time (Type III sum of squares) as variables. |
| Diabetes Treatment Satisfaction Questionnaire-Change Version (DTSQc) - Treatment Satisfaction Score: Week 26 | Week 26 | DTSQc treatment satisfaction score is a 6-item questionnaire which assesses relative change in overall treatment satisfaction. The treatment satisfaction score ranges from -18 to 18, where higher the score the greater the improvement in satisfaction with treatment. The lower the score the greater the deterioration in satisfaction with treatment. |
| Diabetes Treatment Satisfaction Questionnaire-Change Version (DTSQc) - Treatment Satisfaction Score: Week 52 | Week 52 | DTSQc treatment satisfaction score is a 6-item questionnaire which assesses relative change in overall treatment satisfaction. The treatment satisfaction score ranges from -18 to 18, where higher the score the greater the improvement in satisfaction with treatment. The lower the score the greater the deterioration in satisfaction with treatment. |
| Diabetes Treatment Satisfaction Questionnaire-Change Version (DTSQc) - Treatment Satisfaction Score: Week 78 | Week 78 | DTSQc treatment satisfaction score is a 6-item questionnaire which assesses relative change in overall treatment satisfaction. The treatment satisfaction score ranges from -18 to 18, where higher the score the greater the improvement in satisfaction with treatment. The lower the score the greater the deterioration in satisfaction with treatment. |
| 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 during CGM from 22-26 weeks. LS Mean was determined using ANCOVA model using Baseline + Country + Hemoglobin A1c Stratum at Baseline + Type of Basal Insulin used at Baseline + Treatment (Type III sum of squares) as variables. Missing data at baseline were imputed with multiple imputation under assumption of missing at random. Missing data at Week 22-26 were imputed by return-to-baseline multiple imputation approach. |
Countries
Argentina, Hungary, Japan, Poland, Puerto Rico, Slovakia, South Korea, Spain, Taiwan, United States
Participant flow
Recruitment details
Participants underwent a 3 week screening and lead-in period, and a 78-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. | 655 |
| 100 U/mL - Insulin Degludec Participants received 100 U/mL insulin degludec administered SC QD. | 331 |
| Total | 986 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Follow-Up Period | Death | 2 | 0 |
| Follow-Up Period | Protocol Violation | 1 | 0 |
| Follow-Up Period | Withdrawal by Subject | 3 | 0 |
| Treatment Period | Adverse Event | 7 | 1 |
| Treatment Period | Assigned Treatment by Mistake | 6 | 3 |
| Treatment Period | Death | 5 | 2 |
| Treatment Period | Lack of Efficacy | 1 | 0 |
| Treatment Period | Lost to Follow-up | 1 | 5 |
| Treatment Period | Non-Compliance with Study Drug | 5 | 1 |
| Treatment Period | Physician Decision | 5 | 4 |
| Treatment Period | Protocol Violation | 1 | 0 |
| Treatment Period | Sponsor Decision | 1 | 0 |
| Treatment Period | Withdrawal by Subject | 30 | 12 |
Baseline characteristics
| Characteristic | 500 U/mL - Insulin Efsitora | Total | 100 U/mL - Insulin Degludec |
|---|---|---|---|
| Age, Continuous | 60.60 years STANDARD_DEVIATION 10.17 | 60.70 years STANDARD_DEVIATION 10.1 | 60.80 years STANDARD_DEVIATION 9.97 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 179 Participants | 267 Participants | 88 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 476 Participants | 719 Participants | 243 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| HemoglobinA1c (HbA1c) | 7.8 Percentage of HbA1c STANDARD_DEVIATION 0.9 | 7.8 Percentage of HbA1c STANDARD_DEVIATION 0.9 | 7.8 Percentage of HbA1c STANDARD_DEVIATION 0.9 |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 180 Participants | 272 Participants | 92 Participants |
| Race (NIH/OMB) Black or African American | 32 Participants | 52 Participants | 20 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 438 Participants | 656 Participants | 218 Participants |
| Region of Enrollment Argentina | 103 Participants | 155 Participants | 52 Participants |
| Region of Enrollment Hungary | 24 Participants | 38 Participants | 14 Participants |
| Region of Enrollment Japan | 94 Participants | 141 Participants | 47 Participants |
| Region of Enrollment Poland | 59 Participants | 88 Participants | 29 Participants |
| Region of Enrollment Slovakia | 60 Participants | 91 Participants | 31 Participants |
| Region of Enrollment South Korea | 64 Participants | 95 Participants | 31 Participants |
| Region of Enrollment Spain | 52 Participants | 77 Participants | 25 Participants |
| Region of Enrollment Taiwan | 19 Participants | 30 Participants | 11 Participants |
| Region of Enrollment United States | 180 Participants | 271 Participants | 91 Participants |
| Sex: Female, Male Female | 279 Participants | 431 Participants | 152 Participants |
| Sex: Female, Male Male | 376 Participants | 555 Participants | 179 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 7 / 655 | 2 / 331 |
| other Total, other adverse events | 241 / 655 | 102 / 331 |
| serious Total, serious adverse events | 103 / 655 | 37 / 331 |
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. Least Squares (LS) Mean was determined using ANCOVA model with Baseline + Country + Type of Basal Insulin used at Baseline + Treatment (Type III sum of squares) as variables. Missing data at Week 26 were imputed by return-to-baseline multiple imputation approach.
Time frame: Baseline, Week 26
Population: All participants who received at least one dose of study drug and had evaluable data for this outcome at baseline or week 26. Participants who were assigned treatment by mistake were excluded.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 500 U/mL - Insulin Efsitora | Change From Baseline in Hemoglobin A1c (HbA1c) [Noninferiority] | -0.81 Percentage of HbA1c | Standard Error 0.0302 |
| 100 U/mL - Insulin Degludec | Change From Baseline in Hemoglobin A1c (HbA1c) [Noninferiority] | -0.72 Percentage of HbA1c | Standard Error 0.0424 |
95% CI: [-0.191, 0.013]
Secondary
Change From Baseline in Body Weight
Change from baseline in body weight was reported. LS Mean was determined by MMRM model using BASELINE + Treatment + Time + Treatment\*Time (Type III sum of squares) as variables.
Time frame: Baseline, Week 78
Population: All participants who received at least one dose of study drug, had a baseline and at least one post-baseline value for this outcome. Participants who were assigned treatment by mistake were excluded.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 500 U/mL - Insulin Efsitora | Change From Baseline in Body Weight | 2.27 kilograms (kg) | Standard Error 0.133 |
| 100 U/mL - Insulin Degludec | Change From Baseline in Body Weight | 2.20 kilograms (kg) | Standard Error 0.186 |
p-value: 0.75695% CI: [-0.38, 0.52]Mixed Models Analysis
Secondary
Change From Baseline in Fasting Glucose
Fasting glucose measured by Self-Monitoring of Blood Glucose (SMBG). LS Mean was determined using ANCOVA model with Baseline + Country + Type of Basal Insulin at Baseline + Baseline HbA1C Stratum (%) + Treatment (Type III sum of squares) as variables. Missing data at baseline are imputed with multiple imputation under assumption of missing at random. Missing data at Week 26 are imputed by return-to-baseline multiple imputation approach.
Time frame: Baseline, Week 26
Population: All randomized participants who took at least one dose of the study drug and had evaluable data for this outcome at baseline or Week 26 were included. Participants who were assigned treatment by mistake were excluded.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 500 U/mL - Insulin Efsitora | Change From Baseline in Fasting Glucose | -30.97 milligrams per deciliter (mg/dL) | Standard Error 0.943 |
| 100 U/mL - Insulin Degludec | Change From Baseline in Fasting Glucose | -30.13 milligrams per deciliter (mg/dL) | Standard Error 1.323 |
p-value: 0.60595% CI: [-4.01, 2.33]ANCOVA
Secondary
Change From Baseline in Hemoglobin A1c (HbA1c) [Superiority]
HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time. Least Squares (LS) Mean was determined using ANCOVA model with Baseline + Country + Type of Basal Insulin used at Baseline + Treatment (Type III sum of squares) as variables. Missing data at Week 26 were imputed by return-to-baseline multiple imputation approach.
Time frame: Baseline, Week 26
Population: All participants who received at least one dose of study drug and had evaluable data for this outcome at baseline or week 26. Participants who were assigned treatment by mistake were excluded.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 500 U/mL - Insulin Efsitora | Change From Baseline in Hemoglobin A1c (HbA1c) [Superiority] | -0.81 Percentage of HbA1c | Standard Error 0.0302 |
| 100 U/mL - Insulin Degludec | Change From Baseline in Hemoglobin A1c (HbA1c) [Superiority] | -0.72 Percentage of HbA1c | Standard Error 0.0424 |
p-value: 0.08895% CI: [-0.191, 0.013]ANCOVA
Secondary
Change From Baseline in Treatment-Related Impact Measure - Diabetes (TRIM-D)
The TRIM-D is a self-administered instrument, which assesses the impact of diabetes treatment on participants' functioning and well-being across available diabetes treatments. The TRIM-D consists of 28 items each assessed on a 5-point scale. TRIM-D items assess 5 domains of impact: * Treatment Burden (6 items) * Daily Life (5 items) * Diabetes Management (5 items) * Compliance (4 items), and * Psychological Health (8 items) Items within each domain are summed to obtain a raw domain score, which is then transformed to a 0-100 scale, where higher scores indicate a greater impact on participant's functioning and well-being. LS mean was determined using MMRM model with BASELINE + Country + Type of Basal Insulin at Baseline + Baseline HbA1C Stratum (%) + Treatment + Time + Treatment\*Time (Type III sum of squares) as variables.
Time frame: Baseline, Week 26, Week 52, Week 78
Population: All participants who received at least one dose of the study drug, had a baseline and at least one post-baseline value for this outcome. Participants who were assigned treatment by mistake were excluded.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 500 U/mL - Insulin Efsitora | Change From Baseline in Treatment-Related Impact Measure - Diabetes (TRIM-D) | Week 26 | 10.03 Score on a scale | Standard Error 0.424 |
| 500 U/mL - Insulin Efsitora | Change From Baseline in Treatment-Related Impact Measure - Diabetes (TRIM-D) | Week 52 | 10.09 Score on a scale | Standard Error 0.445 |
| 500 U/mL - Insulin Efsitora | Change From Baseline in Treatment-Related Impact Measure - Diabetes (TRIM-D) | Week 78 | 10.33 Score on a scale | Standard Error 0.472 |
| 100 U/mL - Insulin Degludec | Change From Baseline in Treatment-Related Impact Measure - Diabetes (TRIM-D) | Week 26 | 6.88 Score on a scale | Standard Error 0.599 |
| 100 U/mL - Insulin Degludec | Change From Baseline in Treatment-Related Impact Measure - Diabetes (TRIM-D) | Week 52 | 6.53 Score on a scale | Standard Error 0.627 |
| 100 U/mL - Insulin Degludec | Change From Baseline in Treatment-Related Impact Measure - Diabetes (TRIM-D) | Week 78 | 6.98 Score on a scale | Standard Error 0.662 |
Comparison: Week 26p-value: <0.00195% CI: [1.71, 4.59]Mixed Models Analysis
Comparison: Week 52p-value: <0.00195% CI: [2.05, 5.07]Mixed Models Analysis
Comparison: Week 78p-value: <0.00195% CI: [1.75, 4.94]Mixed Models Analysis
Secondary
Diabetes Treatment Satisfaction Questionnaire-Change Version (DTSQc) - Treatment Satisfaction Score: Week 26
DTSQc treatment satisfaction score is a 6-item questionnaire which assesses relative change in overall treatment satisfaction. The treatment satisfaction score ranges from -18 to 18, where higher the score the greater the improvement in satisfaction with treatment. The lower the score the greater the deterioration in satisfaction with treatment.
Time frame: Week 26
Population: All participants who received at least one dose of study drug and had evaluable data for this outcome. Participants who were assigned treatment by mistake were excluded.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 500 U/mL - Insulin Efsitora | Diabetes Treatment Satisfaction Questionnaire-Change Version (DTSQc) - Treatment Satisfaction Score: Week 26 | 14.9 Score on a scale | Standard Deviation 4.47 |
| 100 U/mL - Insulin Degludec | Diabetes Treatment Satisfaction Questionnaire-Change Version (DTSQc) - Treatment Satisfaction Score: Week 26 | 12.3 Score on a scale | Standard Deviation 6.15 |
Secondary
Diabetes Treatment Satisfaction Questionnaire-Change Version (DTSQc) - Treatment Satisfaction Score: Week 52
DTSQc treatment satisfaction score is a 6-item questionnaire which assesses relative change in overall treatment satisfaction. The treatment satisfaction score ranges from -18 to 18, where higher the score the greater the improvement in satisfaction with treatment. The lower the score the greater the deterioration in satisfaction with treatment.
Time frame: Week 52
Population: All participants who received at least one dose of study drug and had evaluable data for this outcome. Participants who were assigned treatment by mistake were excluded.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 500 U/mL - Insulin Efsitora | Diabetes Treatment Satisfaction Questionnaire-Change Version (DTSQc) - Treatment Satisfaction Score: Week 52 | 15.1 Score on a scale | Standard Deviation 4.45 |
| 100 U/mL - Insulin Degludec | Diabetes Treatment Satisfaction Questionnaire-Change Version (DTSQc) - Treatment Satisfaction Score: Week 52 | 12.3 Score on a scale | Standard Deviation 6.1 |
Secondary
Diabetes Treatment Satisfaction Questionnaire-Change Version (DTSQc) - Treatment Satisfaction Score: Week 78
DTSQc treatment satisfaction score is a 6-item questionnaire which assesses relative change in overall treatment satisfaction. The treatment satisfaction score ranges from -18 to 18, where higher the score the greater the improvement in satisfaction with treatment. The lower the score the greater the deterioration in satisfaction with treatment.
Time frame: Week 78
Population: All participants who received at least one dose of study drug and had evaluable data for this outcome. Participants who were assigned treatment by mistake were excluded.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 500 U/mL - Insulin Efsitora | Diabetes Treatment Satisfaction Questionnaire-Change Version (DTSQc) - Treatment Satisfaction Score: Week 78 | 15.4 Score on a scale | Standard Deviation 4.23 |
| 100 U/mL - Insulin Degludec | Diabetes Treatment Satisfaction Questionnaire-Change Version (DTSQc) - Treatment Satisfaction Score: Week 78 | 11.7 Score on a scale | Standard Deviation 6.61 |
Secondary
Hypoglycemia Event Rate
Patient reported events of hypoglycemia - 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 and determined by Negative binomial method using Hemoglobin A1c at Baseline (%) + Treatment, with log (exposure in days/365.25) as variables.
Time frame: Baseline up to Week 78
Population: All participants who received at least one dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 500 U/mL - Insulin Efsitora | Hypoglycemia Event Rate | 0.84 Events per year | Standard Error 0.082 |
| 100 U/mL - Insulin Degludec | Hypoglycemia Event Rate | 0.74 Events per year | Standard Error 0.098 |
p-value: 0.4395% CI: [0.83, 1.56]Negative binomial model
Secondary
Nocturnal Hypoglycemia Event Rate
The event rate of participant-reported clinically significant glucose \<54 mg/dL (3.0 mmol/L) or severe nocturnal hypoglycemia that occurs at night and presumably during sleep between midnight and 6:00 AM), measured during treatment period up to week 78. Group mean is reported here. Group mean is determined by Negative Binomial Model using Number of episodes = Hemoglobin A1c at Baseline (%) + Treatment, with log (exposure in days/365.25) as an offset variable.
Time frame: Baseline up to Week 78
Population: All participants who received at least one dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 500 U/mL - Insulin Efsitora | Nocturnal Hypoglycemia Event Rate | 0.11 Events per year | Standard Error 0.022 |
| 100 U/mL - Insulin Degludec | Nocturnal Hypoglycemia Event Rate | 0.10 Events per year | Standard Error 0.019 |
p-value: 0.89795% CI: [0.62, 1.74]Negative binomial model
Secondary
Percentage of Time in Glucose Range Between 70 and 180 mg/dL (3.9 and 10.0 mmol/L)
Percentage of time in glucose range between 70 and 180 mg/dL (3.9 and 10.0 millimoles per liter (mmol/L)) inclusive measured by continued glucose monitoring (CGM) during CGM session prior to week 26. LS Mean was calculated using ANCOVA model with Baseline + Country + Hemoglobin A1c Stratum at Baseline + Type of Basal Insulin used at Baseline + Treatment (Type III sum of squares) as variables. Missing data during CGM session prior to Week 26 were imputed by return-to-baseline multiple imputation approach.
Time frame: Week 22 to Week 26
Population: All randomized participants who took at least one dose of the study drug and had evaluable data for this outcome at baseline or Week 22-26 were included. Participants who were assigned treatment by mistake were excluded.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 500 U/mL - Insulin Efsitora | Percentage of Time in Glucose Range Between 70 and 180 mg/dL (3.9 and 10.0 mmol/L) | 61.37 Percentage of time | Standard Error 0.676 |
| 100 U/mL - Insulin Degludec | Percentage of Time in Glucose Range Between 70 and 180 mg/dL (3.9 and 10.0 mmol/L) | 60.95 Percentage of time | Standard Error 0.954 |
p-value: 0.72295% CI: [-1.88, 2.72]ANCOVA
Secondary
Percentage of Time in Hyperglycemia Range
Percentage of time in hyperglycemia range with glucose \>180 mg/dL (10.0 mmol/L) measured during the CGM session from 22-26 weeks. LS Mean was determined using ANCOVA model using Baseline + Country + Hemoglobin A1c Stratum at Baseline + Type of Basal Insulin used at Baseline + Treatment (Type III sum of squares) as variables. Missing data at baseline were imputed with multiple imputation under assumption of missing at random. Missing data at Week 22-26 were imputed by return-to-baseline multiple imputation approach.
Time frame: Week 22 to Week 26
Population: All randomized participants who took at least one dose of the study drug and had evaluable data for this outcome at baseline or Week 22-26 were included. Participants who were assigned treatment by mistake were excluded.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 500 U/mL - Insulin Efsitora | Percentage of Time in Hyperglycemia Range | 37.25 Percentage of time | Standard Error 0.7 |
| 100 U/mL - Insulin Degludec | Percentage of Time in Hyperglycemia Range | 38.24 Percentage of time | Standard Error 0.989 |
p-value: 0.41795% CI: [-3.37, 1.4]ANCOVA
Secondary
Percentage of Time in Hypoglycemia Range
Percentage of time in hypoglycemia range with glucose \<54 mg/dL (3.0 mmol/L) measured during CGM from 22-26 weeks. LS Mean was determined using ANCOVA model using Baseline + Country + Hemoglobin A1c Stratum at Baseline + Type of Basal Insulin used at Baseline + Treatment (Type III sum of squares) as variables. Missing data at baseline were imputed with multiple imputation under assumption of missing at random. Missing data at Week 22-26 were imputed by return-to-baseline multiple imputation approach.
Time frame: Week 22 to Week 26
Population: All randomized participants who took at least one dose of the study drug and had evaluable data for this outcome at baseline or Week 22-26 were included. Participants who were assigned treatment by mistake were excluded.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 500 U/mL - Insulin Efsitora | Percentage of Time in Hypoglycemia Range | 0.36 Percentage of time | Standard Error 0.036 |
| 100 U/mL - Insulin Degludec | Percentage of Time in Hypoglycemia Range | 0.22 Percentage of time | Standard Error 0.051 |
p-value: 0.02195% CI: [0.02, 0.27]ANCOVA
Secondary
Weekly Insulin Dose at Week 26
The average weekly insulin dose at Week 26 was reported. LS Mean was determined by mixed model repeated measures (MMRM) model using BASELINE + Country + Type of Basal Insulin at Baseline + Baseline HbA1C Stratum (%) + Treatment + Time + Treatment\*Time (Type III sum of squares) as variables. Variance-covariance structure was set as compound symmetry.
Time frame: Week 26
Population: All participants who received at least one dose of study drug, had a baseline and at least one post-baseline value for this outcome. Participants who were assigned treatment by mistake were excluded.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 500 U/mL - Insulin Efsitora | Weekly Insulin Dose at Week 26 | 333.20 Units per week of insulin | Standard Error 5.93 |
| 100 U/mL - Insulin Degludec | Weekly Insulin Dose at Week 26 | 363.20 Units per week of insulin | Standard Error 8.33 |
p-value: 0.00395% CI: [-50.1, -9.97]Mixed Models Analysis