Trial Outcomes & Findings for A Study of Insulin Efsitora Alfa (LY3209590) Compared With Insulin Degludec in Participants With Type 1 Diabetes Treated With Multiple Daily Injection Therapy (NCT NCT05463744)

Last Updated: 2025-06-24

Results Overview

HbA1c is the glycosylated fraction of hemoglobin A. It is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. Least Squares (LS) mean was determined using Analysis of Covariance (ANCOVA) model with treatment + country + CGM use prior to study entry \[yes/no\]+ carbohydrate counting for prandial insulin\[yes/no\] + baseline value of the dependent variable (Type III sum of squares) as variables. Missing data at Week 26 were imputed by return-to-baseline multiple imputations approach.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

692 participants

Primary outcome timeframe

Baseline, Week 26

Results posted on

2025-06-24

Participant Flow

Participant milestones

Participant milestones
Measure	500 U/mL Insulin Efsitora Alfa Participants who were treated with prestudy basal insulin and prandial insulin therapy (100 units per milliliter (U/mL) Insulin Lispro) received 500 U/mL of insulin efsitora alfa administered once weekly (QW) for 52 weeks as subcutaneous injection, followed by a 5-week safety follow-up.	100 U/mL Insulin Degludec Participants who were treated with prestudy basal insulin and prandial insulin therapy (100 U/mL Insulin Lispro) received 100 U/mL of Insulin Degludec administered once daily (QD) for 52 weeks as subcutaneous injection, followed by a 5-week safety follow-up.
Treatment Period STARTED	343	349
Treatment Period Received at Least One Dose of Study Drug	343	349
Treatment Period COMPLETED	316	319
Treatment Period NOT COMPLETED	27	30
Follow-Up Period STARTED	332	326
Follow-Up Period COMPLETED	328	324
Follow-Up Period NOT COMPLETED	4	2

Reasons for withdrawal

Reasons for withdrawal
Measure	500 U/mL Insulin Efsitora Alfa Participants who were treated with prestudy basal insulin and prandial insulin therapy (100 units per milliliter (U/mL) Insulin Lispro) received 500 U/mL of insulin efsitora alfa administered once weekly (QW) for 52 weeks as subcutaneous injection, followed by a 5-week safety follow-up.	100 U/mL Insulin Degludec Participants who were treated with prestudy basal insulin and prandial insulin therapy (100 U/mL Insulin Lispro) received 100 U/mL of Insulin Degludec administered once daily (QD) for 52 weeks as subcutaneous injection, followed by a 5-week safety follow-up.
Treatment Period Withdrawal by Subject	19	16
Treatment Period Adverse Event	4	4
Treatment Period Pregnancy	0	3
Treatment Period Lost to Follow-up	1	3
Treatment Period Inadvertent enrollment	2	1
Treatment Period Death	0	1
Treatment Period Non-compliance with Study Drug	1	0
Treatment Period Subject Terminated by Sponsor	0	1
Treatment Period Physician Decision	0	1
Follow-Up Period Withdrawal by Subject	3	1
Follow-Up Period Lost to Follow-up	1	1

Baseline Characteristics

A Study of Insulin Efsitora Alfa (LY3209590) Compared With Insulin Degludec in Participants With Type 1 Diabetes Treated With Multiple Daily Injection Therapy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	500 U/mL Insulin Efsitora Alfa n=343 Participants Participants who were treated with prestudy basal insulin and prandial insulin therapy (100 U/mL) Insulin Lispro) received 500 U/mL of insulin efsitora alfa administered once weekly (QW) for 52 weeks as subcutaneous injection, followed by a 5-week safety follow-up	100 U/mL Insulin Degludec n=349 Participants Participants who were treated with prestudy basal insulin and prandial insulin therapy (100 U/mL Insulin Lispro) received 100 U/mL of Insulin Degludec administered QD for 52 weeks as subcutaneous injection, followed by a 5-week safety follow-up.	Total n=692 Participants Total of all reporting groups
Age, Continuous	44.40 years STANDARD_DEVIATION 14.22 • n=5 Participants	43.60 years STANDARD_DEVIATION 14.01 • n=7 Participants	44.00 years STANDARD_DEVIATION 14.11 • n=5 Participants
Sex: Female, Male Female	150 Participants n=5 Participants	158 Participants n=7 Participants	308 Participants n=5 Participants
Sex: Female, Male Male	193 Participants n=5 Participants	191 Participants n=7 Participants	384 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	121 Participants n=5 Participants	116 Participants n=7 Participants	237 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	221 Participants n=5 Participants	230 Participants n=7 Participants	451 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	69 Participants n=5 Participants	73 Participants n=7 Participants	142 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	11 Participants n=5 Participants	13 Participants n=7 Participants	24 Participants n=5 Participants
Race (NIH/OMB) White	259 Participants n=5 Participants	262 Participants n=7 Participants	521 Participants n=5 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment Argentina	98 Participants n=5 Participants	99 Participants n=7 Participants	197 Participants n=5 Participants
Region of Enrollment Japan	48 Participants n=5 Participants	53 Participants n=7 Participants	101 Participants n=5 Participants
Region of Enrollment Poland	66 Participants n=5 Participants	66 Participants n=7 Participants	132 Participants n=5 Participants
Region of Enrollment Slovakia	15 Participants n=5 Participants	17 Participants n=7 Participants	32 Participants n=5 Participants
Region of Enrollment Taiwan	15 Participants n=5 Participants	17 Participants n=7 Participants	32 Participants n=5 Participants
Region of Enrollment United States	101 Participants n=5 Participants	97 Participants n=7 Participants	198 Participants n=5 Participants
HemoglobinA1c (HbA1c)	7.88 Percentage of HbA1c STANDARD_DEVIATION 0.75 • n=5 Participants	7.94 Percentage of HbA1c STANDARD_DEVIATION 0.72 • n=7 Participants	7.91 Percentage of HbA1c STANDARD_DEVIATION 0.73 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Week 26

Population: All randomized participants who received at least one dose of the study drug and had HbA1c measurement at baseline or Week 26. Participants who discontinued the study drug due to inadvertent enrollment were excluded.

Outcome measures

Outcome measures
Measure	500 U/mL Insulin Efsitora Alfa n=341 Participants Participants who are treated with prestudy basal insulin and prandial insulin therapy (100 U/mL) Insulin Lispro) received 500 U/mL of insulin efsitora alfa administered once weekly (QW) for 52 weeks as subcutaneous injection, followed by a 5-week safety follow-up	100 U/mL Insulin Degludec n=348 Participants Participants who are treated with prestudy basal insulin and prandial insulin therapy (100 U/mL Insulin Lispro) received 100 U/mL of Insulin Degludec administered QD for 52 weeks as subcutaneous injection, followed by a 5-week safety follow-up.
Change From Baseline in Hemoglobin A1c (HbA1c) at Week 26 [Noninferiority Analysis]	-0.51 Percentage of HbA1c Standard Error 0.0469	-0.56 Percentage of HbA1c Standard Error 0.0463

SECONDARY outcome

Timeframe: Baseline, Week 26

HbA1c is the glycosylated fraction of hemoglobin A. It is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. LS mean was determined using ANCOVA model with treatment + country + CGM use prior to study entry \[yes/no\] + carbohydrate counting for prandial insulin\[yes/no\] + baseline value of the dependent variable (Type III sum of squares) as variables. Missing data at Week 26 were imputed by return-to-baseline multiple imputations approach.

Outcome measures

Outcome measures
Measure	500 U/mL Insulin Efsitora Alfa n=341 Participants Participants who are treated with prestudy basal insulin and prandial insulin therapy (100 U/mL) Insulin Lispro) received 500 U/mL of insulin efsitora alfa administered once weekly (QW) for 52 weeks as subcutaneous injection, followed by a 5-week safety follow-up	100 U/mL Insulin Degludec n=348 Participants Participants who are treated with prestudy basal insulin and prandial insulin therapy (100 U/mL Insulin Lispro) received 100 U/mL of Insulin Degludec administered QD for 52 weeks as subcutaneous injection, followed by a 5-week safety follow-up.
Change From Baseline in Hemoglobin A1c (HbA1c) at Week 26 [Superiority Analysis]	-0.51 Percentage of HbA1c Standard Error 0.0469	-0.56 Percentage of HbA1c Standard Error 0.0463

SECONDARY outcome

Timeframe: Week 23 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 23-26 were included. Participants who discontinued the study drug due to inadvertent enrollment were excluded.

Percentage of time in glucose range between 70 and 180 milligram per deciliter (mg/dL) \[3.9 and 10.0 millimole per liter (mmol/L)\], measured by continued glucose monitoring (CGM) from week 23 to week 26 inclusive over a 24-Hour Period. The time component of the time-in-range statistic was calculated using the display time recorded by the CGM device. LS mean was determined using ANCOVA model with treatment + country + CGM use prior to study entry \[yes/no\] + carbohydrate counting for prandial insulin dosing \[yes/no\] + Hemoglobin A1c Stratum at Baseline and baseline value of the dependent variable (Type III sum of squares) as variables. Missing data at Week 23-26 were imputed by return-to-baseline multiple imputations approach

Outcome measures

Outcome measures
Measure	500 U/mL Insulin Efsitora Alfa n=339 Participants Participants who are treated with prestudy basal insulin and prandial insulin therapy (100 U/mL) Insulin Lispro) received 500 U/mL of insulin efsitora alfa administered once weekly (QW) for 52 weeks as subcutaneous injection, followed by a 5-week safety follow-up	100 U/mL Insulin Degludec n=347 Participants Participants who are treated with prestudy basal insulin and prandial insulin therapy (100 U/mL Insulin Lispro) received 100 U/mL of Insulin Degludec administered QD for 52 weeks as subcutaneous injection, followed by a 5-week safety follow-up.
Percentage of Time in the Blood Glucose Range Between 70 and 180 mg/dL [3.9 and 10.0 mmol/L] From Week 23 to Week 26	52.54 Percentage of time Standard Error 0.691	52.85 Percentage of time Standard Error 0.684

SECONDARY outcome

Timeframe: Baseline up to Week 52

Population: All randomized participants who received at least one dose of the study drug and had evaluable data for this outcome.

The event rate of participant-reported clinically significant nocturnal hypoglycemia (defined as blood glucose level \<54 mg/dL (3.0 mmol/L) or severe hypoglycemia and occurs at night and presumably during sleep between midnight and 6:00 AM), measured during treatment phase up to week 52. Group mean was reported and determined by Negative binomial model using Number of episodes = Baseline hypoglycemia rate + HbA1c at Baseline (%) + Treatment, with log (exposure in days/365.25) as an offset variable.

Outcome measures

Outcome measures
Measure	500 U/mL Insulin Efsitora Alfa n=343 Participants Participants who are treated with prestudy basal insulin and prandial insulin therapy (100 U/mL) Insulin Lispro) received 500 U/mL of insulin efsitora alfa administered once weekly (QW) for 52 weeks as subcutaneous injection, followed by a 5-week safety follow-up	100 U/mL Insulin Degludec n=349 Participants Participants who are treated with prestudy basal insulin and prandial insulin therapy (100 U/mL Insulin Lispro) received 100 U/mL of Insulin Degludec administered QD for 52 weeks as subcutaneous injection, followed by a 5-week safety follow-up.
Nocturnal Hypoglycemia Event Rate	1.99 events per year Standard Error 0.180	1.96 events per year Standard Error 0.177

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: All randomized participants who received at least one dose of the study drug and had HbA1c measurement at baseline or Week 52. Participants who discontinued the study drug due to inadvertent enrollment were excluded.

HbA1c is the glycosylated fraction of hemoglobin A. It is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. LS mean was determined using ANCOVA model with treatment + country + CGM use prior to study entry \[yes/no\]+ carbohydrate counting for prandial insulin\[yes/no\] + baseline value of the dependent variable (Type III sum of squares) as variables. Missing data at Week 52 were imputed by return-to-baseline multiple imputations approach

Outcome measures

Outcome measures
Measure	500 U/mL Insulin Efsitora Alfa n=341 Participants Participants who are treated with prestudy basal insulin and prandial insulin therapy (100 U/mL) Insulin Lispro) received 500 U/mL of insulin efsitora alfa administered once weekly (QW) for 52 weeks as subcutaneous injection, followed by a 5-week safety follow-up	100 U/mL Insulin Degludec n=348 Participants Participants who are treated with prestudy basal insulin and prandial insulin therapy (100 U/mL Insulin Lispro) received 100 U/mL of Insulin Degludec administered QD for 52 weeks as subcutaneous injection, followed by a 5-week safety follow-up.
Change From Baseline in HbA1c at Week 52 [Noninferiority Analysis]	-0.38 percentage of HbA1c Standard Error 0.0484	-0.40 percentage of HbA1c Standard Error 0.0479

SECONDARY outcome

Timeframe: Baseline, Week 26, and Week 52

Population: All randomized participants who received at least one dose of the study drug and had evaluable data for this outcome at Baseline, Week 26, or Week 52 were included in the analysis. For the Week 26 analysis, data from Baseline or Week 26 were considered, while for the Week 52 analysis, data from Baseline or Week 52 were included. Participants who discontinued the study drug due to inadvertent enrollment were excluded.

Change from baseline in fasting blood glucose measured by self-monitoring blood glucose (SMBG). LS mean was determined using ANCOVA model with treatment, country, CGM use prior to study entry \[yes/no\], carbohydrate counting for prandial insulin dosing \[yes/no\]) and baseline value of the dependent variable as variables. Missing data at Baseline were imputed with multiple imputation with assumption of missing at random. Missing data were imputed by return-to-baseline multiple imputations approach.

Outcome measures

Outcome measures
Measure	500 U/mL Insulin Efsitora Alfa n=341 Participants Participants who are treated with prestudy basal insulin and prandial insulin therapy (100 U/mL) Insulin Lispro) received 500 U/mL of insulin efsitora alfa administered once weekly (QW) for 52 weeks as subcutaneous injection, followed by a 5-week safety follow-up	100 U/mL Insulin Degludec n=348 Participants Participants who are treated with prestudy basal insulin and prandial insulin therapy (100 U/mL Insulin Lispro) received 100 U/mL of Insulin Degludec administered QD for 52 weeks as subcutaneous injection, followed by a 5-week safety follow-up.
Change From Baseline in Fasting Blood Glucose Week 26	-26.67 milligram per deciliter (mg/dL) Standard Error 2.247	-25.45 milligram per deciliter (mg/dL) Standard Error 2.222
Change From Baseline in Fasting Blood Glucose Week 52	-24.78 milligram per deciliter (mg/dL) Standard Error 2.478	-19.93 milligram per deciliter (mg/dL) Standard Error 2.452

SECONDARY outcome

Timeframe: Week 23 to Week 26 and Week 49 to Week 52

Population: All randomized participants who took at least one dose of the study drug and had a baseline and at least one post- baseline value for this outcome. Participants who discontinued the study drug due to inadvertent enrollment were excluded

Glucose variability measured as coefficient of variation (CV) for blood glucose during the CGM session over a 24-hour period, between Week 23 to Week 26 and Week 49 to Week 52 was reported. LS mean was determined using mixed model repeated measures (MMRM) model with BASELINE + Country + Prior CGM use + Carbohydrate counting for Prandial Dose + Hemoglobin A1c Stratum at Baseline + Treatment + Time + Treatment\*Time (Type III sum of squares) as variables. Unstructured variance-covariance structure was used.

Outcome measures

Outcome measures
Measure	500 U/mL Insulin Efsitora Alfa n=331 Participants Participants who are treated with prestudy basal insulin and prandial insulin therapy (100 U/mL) Insulin Lispro) received 500 U/mL of insulin efsitora alfa administered once weekly (QW) for 52 weeks as subcutaneous injection, followed by a 5-week safety follow-up	100 U/mL Insulin Degludec n=332 Participants Participants who are treated with prestudy basal insulin and prandial insulin therapy (100 U/mL Insulin Lispro) received 100 U/mL of Insulin Degludec administered QD for 52 weeks as subcutaneous injection, followed by a 5-week safety follow-up.
Glucose Variability Week 23 to Week 26	33.72 percentage of CV Standard Error 0.230	33.69 percentage of CV Standard Error 0.229
Glucose Variability Week 49 to Week 52	33.69 percentage of CV Standard Error 0.233	33.18 percentage of CV Standard Error 0.233

SECONDARY outcome

Timeframe: Week 49 to Week 52

Population: All randomized participants who received at least one dose of the study drug and had evaluable data for this outcome at baseline or Week 49-52 were included in the analysis. Participants who discontinued the study drug due to inadvertent enrollment were excluded.

Percentage of time spent within the blood glucose range of 70 to 180 mg/dL \[3.9 to 10.0 mmol/L\], as measured during the CGM session over a 24-hour period, from Week 49 to Week 52. LS mean was determined using ANCOVA model with treatment, country, CGM use prior to study entry \[yes/no\], carbohydrate counting for prandial insulin dosing \[yes/no\]) and Hemoglobin A1c Stratum at baseline and baseline value of the dependent variable as variables. Missing data at Baseline were imputed with multiple imputation with assumption of missing at random. Missing data were imputed by return-to-baseline multiple imputations approach.

Outcome measures

Outcome measures
Measure	500 U/mL Insulin Efsitora Alfa n=338 Participants Participants who are treated with prestudy basal insulin and prandial insulin therapy (100 U/mL) Insulin Lispro) received 500 U/mL of insulin efsitora alfa administered once weekly (QW) for 52 weeks as subcutaneous injection, followed by a 5-week safety follow-up	100 U/mL Insulin Degludec n=347 Participants Participants who are treated with prestudy basal insulin and prandial insulin therapy (100 U/mL Insulin Lispro) received 100 U/mL of Insulin Degludec administered QD for 52 weeks as subcutaneous injection, followed by a 5-week safety follow-up.
Percentage of Time in the Blood Glucose Range Between 70 and 180 mg/dL [3.9 and 10.0 mmol/L] From Week 49 to Week 52	50.28 percentage of time Standard Error 0.755	49.74 percentage of time Standard Error 0.744

SECONDARY outcome

Timeframe: Week 26 and Week 52

Population: All randomized participants who received at least one dose of the study drug and had a baseline and at least one post-baseline value for this outcome. Participants who discontinued the study drug due to inadvertent enrollment were excluded.

The insulin dose was recorded daily or weekly in an electronic diary. The average weekly basal insulin dose at Week 26 and Week 52 was reported. LS mean was determined using MMRM model with BASELINE + Hemoglobin A1c Stratum at Baseline + Country + Prior CGM use + Carbohydrate counting for Prandial Dose + Treatment + Time + Treatment\*Time (Type III sum of squares) as variables. Variance-covariance structure was set as compound symmetry.

Outcome measures

Outcome measures
Measure	500 U/mL Insulin Efsitora Alfa n=341 Participants Participants who are treated with prestudy basal insulin and prandial insulin therapy (100 U/mL) Insulin Lispro) received 500 U/mL of insulin efsitora alfa administered once weekly (QW) for 52 weeks as subcutaneous injection, followed by a 5-week safety follow-up	100 U/mL Insulin Degludec n=347 Participants Participants who are treated with prestudy basal insulin and prandial insulin therapy (100 U/mL Insulin Lispro) received 100 U/mL of Insulin Degludec administered QD for 52 weeks as subcutaneous injection, followed by a 5-week safety follow-up.
Basal Insulin Dose Week 26	199.51 Units per week (U/week) Standard Error 4.47	208.47 Units per week (U/week) Standard Error 4.43
Basal Insulin Dose Week 52	204.37 Units per week (U/week) Standard Error 4.50	211.25 Units per week (U/week) Standard Error 4.46

SECONDARY outcome

Timeframe: Week 26 and Week 52

The insulin dose was recorded daily or weekly in an electronic diary. The average daily bolus insulin dose at Week 26 and Week 52 was reported. LS mean was determined using MMRM model with BASELINE + Hemoglobin A1c Stratum at Baseline + Country + Prior CGM use + Carbohydrate counting for Prandial Dose + Treatment + Time + Treatment\*Time (Type III sum of squares) as variables. Variance-covariance structure was set as compound symmetry.

Outcome measures

Outcome measures
Measure	500 U/mL Insulin Efsitora Alfa n=307 Participants Participants who are treated with prestudy basal insulin and prandial insulin therapy (100 U/mL) Insulin Lispro) received 500 U/mL of insulin efsitora alfa administered once weekly (QW) for 52 weeks as subcutaneous injection, followed by a 5-week safety follow-up	100 U/mL Insulin Degludec n=327 Participants Participants who are treated with prestudy basal insulin and prandial insulin therapy (100 U/mL Insulin Lispro) received 100 U/mL of Insulin Degludec administered QD for 52 weeks as subcutaneous injection, followed by a 5-week safety follow-up.
Bolus Insulin Dose Week 26	21.48 Units per day (U/day) Standard Error 0.64	25.25 Units per day (U/day) Standard Error 0.62
Bolus Insulin Dose Week 52	22.62 Units per day (U/day) Standard Error 0.65	26.10 Units per day (U/day) Standard Error 0.63

SECONDARY outcome

Timeframe: Week 26 and Week 52

The average weekly total insulin dose is the sum of the average weekly basal and bolus doses. LS mean was determined using MMRM model with BASELINE + Hemoglobin A1c Stratum at Baseline + Country + Prior CGM use + Carbohydrate counting for Prandial Dose + Treatment + Time + Treatment\*Time (Type III sum of squares) as variables. Variance-covariance structure was set as compound symmetry.

Outcome measures

Outcome measures
Measure	500 U/mL Insulin Efsitora Alfa n=305 Participants Participants who are treated with prestudy basal insulin and prandial insulin therapy (100 U/mL) Insulin Lispro) received 500 U/mL of insulin efsitora alfa administered once weekly (QW) for 52 weeks as subcutaneous injection, followed by a 5-week safety follow-up	100 U/mL Insulin Degludec n=327 Participants Participants who are treated with prestudy basal insulin and prandial insulin therapy (100 U/mL Insulin Lispro) received 100 U/mL of Insulin Degludec administered QD for 52 weeks as subcutaneous injection, followed by a 5-week safety follow-up.
Total Insulin Dose Week 26	343.91 Units per week (U/week) Standard Error 6.72	383.19 Units per week (U/week) Standard Error 6.47
Total Insulin Dose Week 52	355.66 Units per week (U/week) Standard Error 6.81	391.60 Units per week (U/week) Standard Error 6.53

SECONDARY outcome

Timeframe: Week 26 and Week 52

The basal/total insulin dose ratio is the average weekly basal dose divided by the average weekly total dose. LS mean was determined using MMRM model with BASELINE + Hemoglobin A1c Stratum at Baseline + Country + Prior CGM use + Carbohydrate counting for Prandial Dose + Treatment + Time + Treatment\*Time (Type III sum of squares) as variables. Variance-covariance structure was set as compound symmetry.

Outcome measures

Outcome measures
Measure	500 U/mL Insulin Efsitora Alfa n=305 Participants Participants who are treated with prestudy basal insulin and prandial insulin therapy (100 U/mL) Insulin Lispro) received 500 U/mL of insulin efsitora alfa administered once weekly (QW) for 52 weeks as subcutaneous injection, followed by a 5-week safety follow-up	100 U/mL Insulin Degludec n=327 Participants Participants who are treated with prestudy basal insulin and prandial insulin therapy (100 U/mL Insulin Lispro) received 100 U/mL of Insulin Degludec administered QD for 52 weeks as subcutaneous injection, followed by a 5-week safety follow-up.
Basal Insulin Dose to Total Insulin Dose Ratio Week 26	56.4 Percentage of basal/total insulin dose Standard Error 0.69	53.2 Percentage of basal/total insulin dose Standard Error 0.66
Basal Insulin Dose to Total Insulin Dose Ratio Week 52	55.4 Percentage of basal/total insulin dose Standard Error 0.70	52.6 Percentage of basal/total insulin dose Standard Error 0.67

SECONDARY outcome

Timeframe: Baseline up to Week 52

Population: All randomized participants who received at least one dose of the study drug.

Rate of Composite Level 2 and 3 Hypoglycemia Events were reported. Hypoglycemia with glucose \<54 mg/dL (Level 2) or Severe Hypoglycemia confirmed by the investigator to be an event that required assistance for treatment (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 model using Number of episodes = Baseline hypoglycemia rate + HbA1c at Baseline (%) + Treatment, with log (exposure in days/365.25) as an offset variable.

Outcome measures

Outcome measures
Measure	500 U/mL Insulin Efsitora Alfa n=343 Participants Participants who are treated with prestudy basal insulin and prandial insulin therapy (100 U/mL) Insulin Lispro) received 500 U/mL of insulin efsitora alfa administered once weekly (QW) for 52 weeks as subcutaneous injection, followed by a 5-week safety follow-up	100 U/mL Insulin Degludec n=349 Participants Participants who are treated with prestudy basal insulin and prandial insulin therapy (100 U/mL Insulin Lispro) received 100 U/mL of Insulin Degludec administered QD for 52 weeks as subcutaneous injection, followed by a 5-week safety follow-up.
Hypoglycemia Event Rate	14.03 Events per year Standard Error 0.816	11.59 Events per year Standard Error 0.681

SECONDARY outcome

Timeframe: Baseline, Week 26, and Week 52

Population: All randomized participants who received at least one dose of the study drug and had baseline, at least one post-baseline evaluable data for this outcome.

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. Variance-covariance structure was set as compound symmetry.

Outcome measures

Outcome measures
Measure	500 U/mL Insulin Efsitora Alfa n=342 Participants Participants who are treated with prestudy basal insulin and prandial insulin therapy (100 U/mL) Insulin Lispro) received 500 U/mL of insulin efsitora alfa administered once weekly (QW) for 52 weeks as subcutaneous injection, followed by a 5-week safety follow-up	100 U/mL Insulin Degludec n=348 Participants Participants who are treated with prestudy basal insulin and prandial insulin therapy (100 U/mL Insulin Lispro) received 100 U/mL of Insulin Degludec administered QD for 52 weeks as subcutaneous injection, followed by a 5-week safety follow-up.
Change From Baseline in Body Weight Week 26	1.71 kilograms (kg) Standard Error 0.159	1.62 kilograms (kg) Standard Error 0.158
Change From Baseline in Body Weight Week 52	1.96 kilograms (kg) Standard Error 0.160	1.85 kilograms (kg) Standard Error 0.159

SECONDARY outcome

Timeframe: Week 23 to Week 26 and Week 49 to Week 52

Population: All randomized participants who received at least one dose of the study drug and had evaluable data for this outcome at Baseline, Week 23-26, or Week 49-52 were included in the analysis. For the Week 23-26 analysis, data from Baseline or Week 23-26 were considered, while for the Week 49-52 analysis, data from Baseline or Week 49-52 were included. Participants who discontinued the study drug due to inadvertent enrollment were excluded.

Percentage of time spent in the hypoglycemia range with blood glucose \< 54 mg/dL (3.0 mmol/L), as measured during the CGM session over a 24-hour period from week 23 to week 26 and week 49 to week 52 was reported. LS Mean was determined by ANCOVA model using treatment + country + CGM use prior to study entry \[yes/no\] + carbohydrate counting for prandial insulin dosing \[yes/no\] + Hemoglobin A1c Stratum at Baseline and baseline value of the dependent variable (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 23-26 and week 49-52 were imputed by return-to-baseline multiple imputations approach.

Outcome measures

Outcome measures
Measure	500 U/mL Insulin Efsitora Alfa n=339 Participants Participants who are treated with prestudy basal insulin and prandial insulin therapy (100 U/mL) Insulin Lispro) received 500 U/mL of insulin efsitora alfa administered once weekly (QW) for 52 weeks as subcutaneous injection, followed by a 5-week safety follow-up	100 U/mL Insulin Degludec n=347 Participants Participants who are treated with prestudy basal insulin and prandial insulin therapy (100 U/mL Insulin Lispro) received 100 U/mL of Insulin Degludec administered QD for 52 weeks as subcutaneous injection, followed by a 5-week safety follow-up.
Percentage of Time in Hypoglycemia Range With Blood Glucose <54 mg/dL (3.0 mmol/L) Week 23 to Week 26	0.75 percentage of time Standard Error 0.058	0.72 percentage of time Standard Error 0.057
Percentage of Time in Hypoglycemia Range With Blood Glucose <54 mg/dL (3.0 mmol/L) Week 49 to Week 52	0.74 percentage of time Standard Error 0.053	0.64 percentage of time Standard Error 0.052

SECONDARY outcome

Timeframe: Week 23 to Week 26

Population: All randomized participants who received at least one dose of the study drug and had evaluable data for this outcome at baseline or Week 23-26 were included in the analysis. Participants who discontinued the study drug due to inadvertent enrollment were excluded

Percentage of time spent in the hyperglycemia range with blood glucose greater than (\>) 180 mg/dL (10.0 mmol/L), as measured during the CGM session over a 24-hour period from Week 23 to Week 26 was reported. LS Mean was determined by ANCOVA model using treatment + country + CGM use prior to study entry \[yes/no\] + carbohydrate counting for prandial insulin dosing \[yes/no\] + Hemoglobin A1c Stratum at Baseline and baseline value of the dependent variable (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 23-week 26 were imputed by return-to-baseline multiple imputations approach.

Outcome measures

Outcome measures
Measure	500 U/mL Insulin Efsitora Alfa n=339 Participants Participants who are treated with prestudy basal insulin and prandial insulin therapy (100 U/mL) Insulin Lispro) received 500 U/mL of insulin efsitora alfa administered once weekly (QW) for 52 weeks as subcutaneous injection, followed by a 5-week safety follow-up	100 U/mL Insulin Degludec n=347 Participants Participants who are treated with prestudy basal insulin and prandial insulin therapy (100 U/mL Insulin Lispro) received 100 U/mL of Insulin Degludec administered QD for 52 weeks as subcutaneous injection, followed by a 5-week safety follow-up.
Percentage of Time in Hyperglycemia Range With Blood Glucose >180 mg/dL (10.0 mmol/L) From Week 23 to Week 26	44.29 percentage of time Standard Error 0.743	44.29 percentage of time Standard Error 0.735

SECONDARY outcome

Timeframe: Week 49 to Week 52

Percentage of time spent in the hyperglycemia range with blood glucose greater than (\>) 180 mg/dL (10.0 mmol/L), as measured during the CGM session over a 24-hour period from Week 49 to Week 52 was reported. LS Mean was determined by ANCOVA model using treatment + country + CGM use prior to study entry \[yes/no\] + carbohydrate counting for prandial insulin dosing \[yes/no\] + Hemoglobin A1c Stratum at Baseline and baseline value of the dependent variable (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 49-week 52 were imputed by return-to-baseline multiple imputations approach.

Outcome measures

Outcome measures
Measure	500 U/mL Insulin Efsitora Alfa n=338 Participants Participants who are treated with prestudy basal insulin and prandial insulin therapy (100 U/mL) Insulin Lispro) received 500 U/mL of insulin efsitora alfa administered once weekly (QW) for 52 weeks as subcutaneous injection, followed by a 5-week safety follow-up	100 U/mL Insulin Degludec n=347 Participants Participants who are treated with prestudy basal insulin and prandial insulin therapy (100 U/mL Insulin Lispro) received 100 U/mL of Insulin Degludec administered QD for 52 weeks as subcutaneous injection, followed by a 5-week safety follow-up.
Percentage of Time in Hyperglycemia Range With Blood Glucose >180 mg/dL (10.0 mmol/L) From Week 49 to Week 52	46.73 percentage of time Standard Error 0.811	47.56 percentage of time Standard Error 0.797

SECONDARY outcome

Timeframe: Week 26

Population: All randomized participants who received at least one dose of the study drug and had evaluable data for this outcome. Participants who discontinued the study drug due to inadvertent enrollment were excluded.

The Diabetes Treatment Satisfaction Questionnaire change (DTSQc) score is used to assess relative change in participant satisfaction from baseline. The questionnaire consists of 8 items, 6 of which measure Treatment Satisfaction, dealing with: 1. satisfaction with current treatment; 2. convenience of the treatment; 3. flexibility; 4. satisfaction with own understanding of participant's diabetes; 5. how likely to recommend their present treatment; and 6. how satisfied to continue with their present treatment. Each item is rated on a 7-point Likert scale (which ranges from -3 (much less satisfied) to +3 (much more satisfied). The scores from the 6 treatment satisfaction items are summed to a Total Treatment Satisfaction Score, which ranges from -18 (much less satisfied) to +18 (much more satisfied). Higher the score the greater the improvement in satisfaction with treatment. The lower the score the greater the deterioration in satisfaction with treatment.

Outcome measures

Outcome measures
Measure	500 U/mL Insulin Efsitora Alfa n=306 Participants Participants who are treated with prestudy basal insulin and prandial insulin therapy (100 U/mL) Insulin Lispro) received 500 U/mL of insulin efsitora alfa administered once weekly (QW) for 52 weeks as subcutaneous injection, followed by a 5-week safety follow-up	100 U/mL Insulin Degludec n=314 Participants Participants who are treated with prestudy basal insulin and prandial insulin therapy (100 U/mL Insulin Lispro) received 100 U/mL of Insulin Degludec administered QD for 52 weeks as subcutaneous injection, followed by a 5-week safety follow-up.
Diabetes Treatment Satisfaction as Measured by the Diabetes Treatment Satisfaction Questionnaire, Change Version (DTSQc) at Week 26	14.4 score on a scale Standard Deviation 4.53	13.2 score on a scale Standard Deviation 5.20

SECONDARY outcome

Timeframe: Week 52

The DTSQc score is used to assess relative change in participant satisfaction from baseline. The questionnaire consists of 8 items, 6 of which measure Treatment Satisfaction, dealing with: 1. satisfaction with current treatment; 2. convenience of the treatment; 3. flexibility; 4. satisfaction with own understanding of participant's diabetes; 5. how likely to recommend their present treatment; and 6. how satisfied to continue with their present treatment. Each item is rated on a 7-point Likert scale (which ranges from -3 (much less satisfied) to +3 (much more satisfied). The scores from the 6 treatment satisfaction items are summed to a Total Treatment Satisfaction Score, which ranges from -18 (much less satisfied) to +18 (much more satisfied). Higher the score the greater the improvement in satisfaction with treatment. The lower the score the greater the deterioration in satisfaction with treatment.

Outcome measures

Outcome measures
Measure	500 U/mL Insulin Efsitora Alfa n=310 Participants Participants who are treated with prestudy basal insulin and prandial insulin therapy (100 U/mL) Insulin Lispro) received 500 U/mL of insulin efsitora alfa administered once weekly (QW) for 52 weeks as subcutaneous injection, followed by a 5-week safety follow-up	100 U/mL Insulin Degludec n=312 Participants Participants who are treated with prestudy basal insulin and prandial insulin therapy (100 U/mL Insulin Lispro) received 100 U/mL of Insulin Degludec administered QD for 52 weeks as subcutaneous injection, followed by a 5-week safety follow-up.
Diabetes Treatment Satisfaction as Measured by the Diabetes Treatment Satisfaction Questionnaire, Change Version (DTSQc) at Week 52	14.4 score on a scale Standard Deviation 5.31	12.8 score on a scale Standard Deviation 5.67

SECONDARY outcome

Timeframe: Baseline, Week 26, and Week 52

Population: All randomized 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 discontinued the study drug due to inadvertent enrollment were excluded.

The SF-36v2 is a participant-reported measure designed to assess health status using 36 items across 8 domains: Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional, and Mental Health. The 8 health domains are aggregated into two summary scores known as the physical component summary (PCS) score and the mental component summary (MCS) score. Scoring of each domain and both summary scores are norm based and presented in the form of T-scores, with a mean of 50 and a standard deviation of 10. Higher scores indicate better levels of function and/or better health. Range cannot be specified in norm-based scores. LS Mean was determined by MMRM model with Baseline + Country + Carbohydrate counting for Prandial Dose + Prior CGM use + Hemoglobin A1c Stratum at Baseline + Treatment + Time + Treatment\*Time (Type III sum of squares). as variables. Unstructured variance-covariance structure was used.

Outcome measures

Outcome measures
Measure	500 U/mL Insulin Efsitora Alfa n=327 Participants Participants who are treated with prestudy basal insulin and prandial insulin therapy (100 U/mL) Insulin Lispro) received 500 U/mL of insulin efsitora alfa administered once weekly (QW) for 52 weeks as subcutaneous injection, followed by a 5-week safety follow-up	100 U/mL Insulin Degludec n=330 Participants Participants who are treated with prestudy basal insulin and prandial insulin therapy (100 U/mL Insulin Lispro) received 100 U/mL of Insulin Degludec administered QD for 52 weeks as subcutaneous injection, followed by a 5-week safety follow-up.
Change From Baseline in Short Form-36 Version 2 (SF-36 v2) Acute Form (Physical-Component and Mental-Component) Scores Physical Component Score: Week 26	0.19 T-score Standard Error 0.275	-0.24 T-score Standard Error 0.272
Change From Baseline in Short Form-36 Version 2 (SF-36 v2) Acute Form (Physical-Component and Mental-Component) Scores Physical Component Score: Week 52	0.48 T-score Standard Error 0.262	-0.25 T-score Standard Error 0.260
Change From Baseline in Short Form-36 Version 2 (SF-36 v2) Acute Form (Physical-Component and Mental-Component) Scores Mental Component Score: Week 26	0.58 T-score Standard Error 0.419	0.36 T-score Standard Error 0.415
Change From Baseline in Short Form-36 Version 2 (SF-36 v2) Acute Form (Physical-Component and Mental-Component) Scores Mental Component Score: Week 52	0.61 T-score Standard Error 0.419	0.16 T-score Standard Error 0.417

Adverse Events

500 U/mL Insulin Efsitora Alfa

Serious events: 45 serious events

Other events: 117 other events

Deaths: 0 deaths

100 U/mL Insulin Degludec

Serious events: 24 serious events

Other events: 119 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	500 U/mL Insulin Efsitora Alfa n=343 participants at risk Participants who were treated with prestudy basal insulin and prandial insulin therapy (100 U/mL) Insulin Lispro) received 500 U/mL of insulin efsitora alfa administered once weekly (QW) for 52 weeks as subcutaneous injection, followed by a 5-week safety follow-up.	100 U/mL Insulin Degludec n=349 participants at risk Participants who were treated with prestudy basal insulin and prandial insulin therapy (100 U/mL Insulin Lispro) received 100 U/mL of Insulin Degludec administered QD for 52 weeks as subcutaneous injection, followed by a 5-week safety follow-up.
Infections and infestations Covid-19	4.7% 16/343 • Number of events 16 • Baseline to end of safety follow-up (up to 57 weeks) All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Participants were analyzed based on the actual treatment they received.	6.6% 23/349 • Number of events 24 • Baseline to end of safety follow-up (up to 57 weeks) All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Participants were analyzed based on the actual treatment they received.
Infections and infestations Influenza	7.9% 27/343 • Number of events 30 • Baseline to end of safety follow-up (up to 57 weeks) All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Participants were analyzed based on the actual treatment they received.	5.2% 18/349 • Number of events 22 • Baseline to end of safety follow-up (up to 57 weeks) All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Participants were analyzed based on the actual treatment they received.
Infections and infestations Nasopharyngitis	11.7% 40/343 • Number of events 45 • Baseline to end of safety follow-up (up to 57 weeks) All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Participants were analyzed based on the actual treatment they received.	12.0% 42/349 • Number of events 54 • Baseline to end of safety follow-up (up to 57 weeks) All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Participants were analyzed based on the actual treatment they received.
Infections and infestations Upper respiratory tract infection	7.0% 24/343 • Number of events 29 • Baseline to end of safety follow-up (up to 57 weeks) All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Participants were analyzed based on the actual treatment they received.	8.6% 30/349 • Number of events 35 • Baseline to end of safety follow-up (up to 57 weeks) All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Participants were analyzed based on the actual treatment they received.
Infections and infestations Urinary tract infection	6.1% 21/343 • Number of events 24 • Baseline to end of safety follow-up (up to 57 weeks) All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Participants were analyzed based on the actual treatment they received.	3.2% 11/349 • Number of events 16 • Baseline to end of safety follow-up (up to 57 weeks) All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Participants were analyzed based on the actual treatment they received.
Skin and subcutaneous tissue disorders Dermatitis contact	5.5% 19/343 • Number of events 20 • Baseline to end of safety follow-up (up to 57 weeks) All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Participants were analyzed based on the actual treatment they received.	4.6% 16/349 • Number of events 16 • Baseline to end of safety follow-up (up to 57 weeks) All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. Participants were analyzed based on the actual treatment they received.

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 08005455979

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60