Trial Outcomes & Findings for A Study of Insulin Efsitora Alfa (LY3209590) Compared to Degludec in Adults With Type 2 Diabetes Who Are Starting Basal Insulin for the First Time (NCT NCT05362058)

NCT ID: NCT05362058

Last Updated: 2025-05-16

Results Overview

* HbA1c is the glycosylated fraction of hemoglobin A. It is measured to identify average plasma glucose concentration over prolonged periods of time. * Least Squares (LS) mean was determined using Analysis of Covariance (ANCOVA) model with Baseline + Country + GLP-1 RA Use at Randomization Flag + SU Use at Randomization Flag + Treatment (Type III sum of squares) as variables. Missing data at Week 52 were imputed by return-to-baseline multiple imputations approach.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

928 participants

Primary outcome timeframe

Baseline, Week 52

Results posted on

2025-05-16

Participant Flow

Participants continued their protocol-specified stable therapy with 1 to 3 non-insulin antihyperglycemic medications, including glucagon-like peptide-1 receptor agonists (GLP-1 RA), as well as non-GLP-1 receptor agonists such as dipeptidyl peptidase-4 (DPP-4) inhibitors, sodium-glucose cotransporter 2 (SGLT2) inhibitors, biguanides (e.g., metformin), alpha-glucosidase inhibitors, sulfonylureas (SUs), or thiazolidinediones throughout the study, at the discretion of the investigator.

Participant milestones

Participant milestones
Measure	500 U/mL - Insulin Efsitora Alfa \- Participants received 500 units per milliliter (U/mL) of insulin efsitora alfa administered subcutaneously (SC) once weekly (QW) over a 52-week treatment period, followed by a 5-week safety follow-up period.	100 U/mL - Insulin Degludec \- Participants received 100 U/mL insulin degludec administered SC once daily (QD) over a 52-week treatment period, followed by a 5-week safety follow-up period.
Treatment Period STARTED	466	462
Treatment Period Participants Using GLP-1 Receptor Agonists	232	232
Treatment Period Participants Not Using GLP-1 Receptor Agonists	234	230
Treatment Period Received at Least One Dose of Study Drug	466	462
Treatment Period COMPLETED	441	439
Treatment Period NOT COMPLETED	25	23
Follow-Up Period STARTED	445	444
Follow-Up Period COMPLETED	441	439
Follow-Up Period NOT COMPLETED	4	5

Reasons for withdrawal

Reasons for withdrawal
Measure	500 U/mL - Insulin Efsitora Alfa \- Participants received 500 units per milliliter (U/mL) of insulin efsitora alfa administered subcutaneously (SC) once weekly (QW) over a 52-week treatment period, followed by a 5-week safety follow-up period.	100 U/mL - Insulin Degludec \- Participants received 100 U/mL insulin degludec administered SC once daily (QD) over a 52-week treatment period, followed by a 5-week safety follow-up period.
Treatment Period Adverse Event	3	3
Treatment Period Assigned treatment by mistake	3	4
Treatment Period Death	1	1
Treatment Period Lost to Follow-up	6	3
Treatment Period Non-compliance with study drug	0	1
Treatment Period Physician Decision	1	0
Treatment Period Protocol deviation	1	0
Treatment Period Withdrawal by Subject	10	11
Follow-Up Period Death	1	0
Follow-Up Period Lost to Follow-up	2	1
Follow-Up Period Protocol deviation	1	1
Follow-Up Period Withdrawal by Subject	0	3

Baseline Characteristics

A Study of Insulin Efsitora Alfa (LY3209590) Compared to Degludec in Adults With Type 2 Diabetes Who Are Starting Basal Insulin for the First Time

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	500 U/mL - Insulin Efsitora Alfa n=466 Participants Participants received 500 U/mL insulin efsitora alfa administered SC QW over a 52-week treatment period, followed by a 5-week safety follow-up period.	100 U/mL - Insulin Degludec n=462 Participants Participants received 100 U/mL insulin degludec administered SC QD over a 52-week treatment period, followed by a 5-week safety follow-up period.	Total n=928 Participants Total of all reporting groups
Age, Continuous	57.6 years STANDARD_DEVIATION 10.6 • n=5 Participants	57.3 years STANDARD_DEVIATION 11 • n=7 Participants	57.4 years STANDARD_DEVIATION 10.8 • n=5 Participants
Sex: Female, Male Female	185 Participants n=5 Participants	197 Participants n=7 Participants	382 Participants n=5 Participants
Sex: Female, Male Male	281 Participants n=5 Participants	265 Participants n=7 Participants	546 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	119 Participants n=5 Participants	123 Participants n=7 Participants	242 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	345 Participants n=5 Participants	335 Participants n=7 Participants	680 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	34 Participants n=5 Participants	36 Participants n=7 Participants	70 Participants n=5 Participants
Race (NIH/OMB) Asian	163 Participants n=5 Participants	164 Participants n=7 Participants	327 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	31 Participants n=5 Participants	27 Participants n=7 Participants	58 Participants n=5 Participants
Race (NIH/OMB) White	235 Participants n=5 Participants	233 Participants n=7 Participants	468 Participants n=5 Participants
Race (NIH/OMB) More than one race	3 Participants n=5 Participants	2 Participants n=7 Participants	5 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 Brazil	40 Participants n=5 Participants	43 Participants n=7 Participants	83 Participants n=5 Participants
Region of Enrollment Canada	18 Participants n=5 Participants	23 Participants n=7 Participants	41 Participants n=5 Participants
Region of Enrollment China	67 Participants n=5 Participants	67 Participants n=7 Participants	134 Participants n=5 Participants
Region of Enrollment Czechia	48 Participants n=5 Participants	50 Participants n=7 Participants	98 Participants n=5 Participants
Region of Enrollment Germany	30 Participants n=5 Participants	27 Participants n=7 Participants	57 Participants n=5 Participants
Region of Enrollment Greece	17 Participants n=5 Participants	15 Participants n=7 Participants	32 Participants n=5 Participants
Region of Enrollment Japan	71 Participants n=5 Participants	73 Participants n=7 Participants	144 Participants n=5 Participants
Region of Enrollment Mexico	50 Participants n=5 Participants	49 Participants n=7 Participants	99 Participants n=5 Participants
Region of Enrollment South Korea	11 Participants n=5 Participants	8 Participants n=7 Participants	19 Participants n=5 Participants
Region of Enrollment United States	114 Participants n=5 Participants	107 Participants n=7 Participants	221 Participants n=5 Participants
HemoglobinA1c (HbA1c)	8.21 Percentage of HbA1c STANDARD_DEVIATION 0.96 • n=5 Participants	8.23 Percentage of HbA1c STANDARD_DEVIATION 0.96 • n=7 Participants	8.22 Percentage of HbA1c STANDARD_DEVIATION 0.96 • n=5 Participants

PRIMARY 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.

Outcome measures

Outcome measures
Measure	500 U/mL - Insulin Efsitora Alfa n=463 Participants Participants received 500 U/mL insulin efsitora alfa administered SC QW over a 52-week treatment period, followed by a 5-week safety follow-up period.	100 U/mL - Insulin Degludec n=458 Participants Participants received 100 U/mL insulin degludec administered SC QD over a 52-week treatment period, followed by a 5-week safety follow-up period.
Change From Baseline in HbA1c at Week 52 [Noninferiority Analysis]	-1.26 Percentage of HbA1c Standard Error 0.0470	-1.17 Percentage of HbA1c Standard Error 0.0473

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: All randomized participants who continued using GLP-1 receptor agonists and received at least one dose of the study drug, 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 to identify average plasma glucose concentration over prolonged periods of time. * LS mean was determined using ANCOVA model with Baseline + Country + SU Use at Randomization Flag + Treatment (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=230 Participants Participants received 500 U/mL insulin efsitora alfa administered SC QW over a 52-week treatment period, followed by a 5-week safety follow-up period.	100 U/mL - Insulin Degludec n=231 Participants Participants received 100 U/mL insulin degludec administered SC QD over a 52-week treatment period, followed by a 5-week safety follow-up period.
Change From Baseline in HbA1c at Week 52 in Participants Using GLP-1 Receptor Agonists [Noninferiority Analysis]	-1.26 Percentage of HbA1c Standard Error 0.0699	-1.19 Percentage of HbA1c Standard Error 0.0696

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: All randomized participants who were not using GLP-1 receptor agonists and received at least one dose of the study drug, had HbA1c measurement at baseline or Week 52. Participants who discontinued the study drug due to inadvertent enrollment were excluded.

Outcome measures

Outcome measures
Measure	500 U/mL - Insulin Efsitora Alfa n=233 Participants Participants received 500 U/mL insulin efsitora alfa administered SC QW over a 52-week treatment period, followed by a 5-week safety follow-up period.	100 U/mL - Insulin Degludec n=227 Participants Participants received 100 U/mL insulin degludec administered SC QD over a 52-week treatment period, followed by a 5-week safety follow-up period.
Change From Baseline in HbA1c at Week 52 in Participants Not Using GLP-1 Receptor Agonists [Noninferiority Analysis]	-1.26 Percentage of HbA1c Standard Error 0.0627	-1.15 Percentage of HbA1c Standard Error 0.0639

SECONDARY outcome

Timeframe: Baseline, Week 52

* HbA1c is the glycosylated fraction of hemoglobin A. It is measured to identify average plasma glucose concentration over prolonged periods of time. * LS mean was determined using ANCOVA model with Baseline + Country + GLP-1 RA Use at Randomization Flag + SU Use at Randomization Flag + Treatment (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=463 Participants Participants received 500 U/mL insulin efsitora alfa administered SC QW over a 52-week treatment period, followed by a 5-week safety follow-up period.	100 U/mL - Insulin Degludec n=458 Participants Participants received 100 U/mL insulin degludec administered SC QD over a 52-week treatment period, followed by a 5-week safety follow-up period.
Change From Baseline in HbA1c at Week 52 [Superiority Analysis]	-1.26 Percentage of HbA1c Standard Error 0.0470	-1.17 Percentage of HbA1c Standard Error 0.0473

SECONDARY outcome

Timeframe: Week 48 to Week 52

Population: All randomized participants who took at least 1 dose of the study drug and had CGM data collected using the Dexcom G6 system at baseline or Week 48-52 were included. Participants who discontinued the study drug due to inadvertent enrollment were excluded. As pre-specified in the statistical analysis plan, outcome data were analyzed only from CGM data collected by the Dexcom G6 system.

* Percentage of time spent within the blood glucose range of 70 to 180 milligrams per deciliter (mg/dL) \[3.9 to 10.0 millimoles per liter (mmol/L)\], as measured during the continuous glucose monitoring (CGM) session over a 24-hour period, from Week 48 to Week 52. * LS mean was determined using ANCOVA model with Baseline + Country + HbA1c Stratum at Baseline + GLP-1 RA Use at Randomization + SU Use at Randomization + Treatment (Type III sum of squares) as variables. Missing data at baseline were imputed using multiple imputation under the assumption of missing at random, while missing data at Week 48-52 were imputed using a return-to-baseline multiple imputation approach.

Outcome measures

Outcome measures
Measure	500 U/mL - Insulin Efsitora Alfa n=387 Participants Participants received 500 U/mL insulin efsitora alfa administered SC QW over a 52-week treatment period, followed by a 5-week safety follow-up period.	100 U/mL - Insulin Degludec n=381 Participants Participants received 100 U/mL insulin degludec administered SC QD over a 52-week treatment period, followed by a 5-week safety follow-up period.
Percentage of Time in the Blood Glucose Range Between 70 and 180 mg/dL [3.9 and 10.0 mmol/L] - Week 48 to Week 52	64.27 Percentage of time Standard Error 1.076	61.18 Percentage of time Standard Error 1.085

SECONDARY 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.

* HbA1c is the glycosylated fraction of hemoglobin A. It is measured to identify average plasma glucose concentration over prolonged periods of time. * LS mean was determined using ANCOVA model with Baseline + Country + GLP-1 RA Use at Randomization Flag + SU Use at Randomization Flag + Treatment (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=463 Participants Participants received 500 U/mL insulin efsitora alfa administered SC QW over a 52-week treatment period, followed by a 5-week safety follow-up period.	100 U/mL - Insulin Degludec n=458 Participants Participants received 100 U/mL insulin degludec administered SC QD over a 52-week treatment period, followed by a 5-week safety follow-up period.
Change From Baseline in HbA1c at Week 26 [Superiority Analysis]	-1.37 Percentage of HbA1c Standard Error 0.0394	-1.30 Percentage of HbA1c Standard Error 0.0397

SECONDARY outcome

Timeframe: Week 22 to Week 26

Population: All randomized participants who took at least 1 dose of the study drug and had CGM data collected using the Dexcom G6 system at baseline or Week 22-26 were included. Participants who discontinued the study drug due to inadvertent enrollment were excluded. As pre-specified in the statistical analysis plan, outcome data were analyzed only from CGM data collected by the Dexcom G6 system.

* 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 22 to Week 26. * LS mean was determined using ANCOVA model with Baseline + Country + HbA1c Stratum at Baseline + GLP-1 RA Use at Randomization + SU Use at Randomization + Treatment (Type III sum of squares) as variables. Missing data at baseline were imputed using multiple imputation under the assumption of missing at random, while missing data at Week 22-26 were imputed using a return-to-baseline multiple imputation approach.

Outcome measures

Outcome measures
Measure	500 U/mL - Insulin Efsitora Alfa n=385 Participants Participants received 500 U/mL insulin efsitora alfa administered SC QW over a 52-week treatment period, followed by a 5-week safety follow-up period.	100 U/mL - Insulin Degludec n=382 Participants Participants received 100 U/mL insulin degludec administered SC QD over a 52-week treatment period, followed by a 5-week safety follow-up period.
Percentage of Time in the Blood Glucose Range Between 70 and 180 mg/dL [3.9 and 10.0 mmol/L] - Week 22 to Week 26	66.12 Percentage of time Standard Error 0.991	65.85 Percentage of time Standard Error 0.990

SECONDARY outcome

Timeframe: Baseline, Week 26, Week 52

Population: All randomized participants who received at least 1 dose of the study drug and had evaluable data for this outcome at Baseline, Week 26, or Week 52 were included.For the Week 26 analysis data from Baseline and Week 26 were used and for Week 52 analysis data from Baseline and Week 52 data were used.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).

Outcome measures

Outcome measures
Measure	500 U/mL - Insulin Efsitora Alfa n=458 Participants Participants received 500 U/mL insulin efsitora alfa administered SC QW over a 52-week treatment period, followed by a 5-week safety follow-up period.	100 U/mL - Insulin Degludec n=451 Participants Participants received 100 U/mL insulin degludec administered SC QD over a 52-week treatment period, followed by a 5-week safety follow-up period.
Change From Baseline in Fasting Blood Glucose (FBG) Week 26	-57.86 Milligram per deciliter (mg/dL) Standard Error 1.491	-63.04 Milligram per deciliter (mg/dL) Standard Error 1.500
Change From Baseline in Fasting Blood Glucose (FBG) Week 52	-59.77 Milligram per deciliter (mg/dL) Standard Error 1.400	-59.97 Milligram per deciliter (mg/dL) Standard Error 1.405

SECONDARY outcome

Timeframe: Week 22 to Week 26 and Week 48 to Week 52

Population: All randomized participants who took at least 1 dose of the study drug and had Dexcom G6 system CGM data collected at baseline and at least 1 post-baseline value were included. Participants who discontinued the study drug due to inadvertent enrollment were excluded. As pre-specified in the statistical analysis plan, outcome data were analyzed only from CGM data collected by the Dexcom G6 system.

* Glucose variability measured as coefficient of variation (CV) for blood glucose during the CGM session over a 24-hour period, between Week 22 to Week 26 and Week 48 to Week 52 was reported. * LS mean was determined using Mixed Model Repeated Measures (MMRM) model with Baseline + Country +HbA1c Stratum at Baseline + GLP-1 RA Use at Randomization Flag + SU Use at Randomization Flag + Treatment + Time + Treatment\*Time (Type III sum of squares) as variables.

Outcome measures

Outcome measures
Measure	500 U/mL - Insulin Efsitora Alfa n=368 Participants Participants received 500 U/mL insulin efsitora alfa administered SC QW over a 52-week treatment period, followed by a 5-week safety follow-up period.	100 U/mL - Insulin Degludec n=360 Participants Participants received 100 U/mL insulin degludec administered SC QD over a 52-week treatment period, followed by a 5-week safety follow-up period.
Glucose Variability Week 22 to Week 26	26.31 Percentage of CV Standard Error 0.250	26.67 Percentage of CV Standard Error 0.251
Glucose Variability Week 48 to Week 52	26.29 Percentage of CV Standard Error 0.243	26.81 Percentage of CV Standard Error 0.246

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 calculated based on the participant's entry of daily or weekly insulin doses 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 Country + HbA1c Stratum at Baseline + GLP-1 RA Use at Randomization Flag + SU Use at Randomization Flag + Treatment + Time + Treatment\*Time (Type III sum of squares) as variables.

Outcome measures

Outcome measures
Measure	500 U/mL - Insulin Efsitora Alfa n=463 Participants Participants received 500 U/mL insulin efsitora alfa administered SC QW over a 52-week treatment period, followed by a 5-week safety follow-up period.	100 U/mL - Insulin Degludec n=457 Participants Participants received 100 U/mL insulin degludec administered SC QD over a 52-week treatment period, followed by a 5-week safety follow-up period.
Basal Insulin Dose Week 26	292.8 Units per week (U/week) Standard Error 6.30	305.9 Units per week (U/week) Standard Error 6.17
Basal Insulin Dose Week 52	314.7 Units per week (U/week) Standard Error 6.25	334.4 Units per week (U/week) Standard Error 6.22

SECONDARY outcome

Timeframe: Baseline up to Week 52

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

* A hypoglycemic event with blood glucose (BG) levels of less than (\<) 54 mg/dL (3.0 mmol/L) \[Level 2\] or Severe Hypoglycemia \[Level 3\] was reported. A severe hypoglycemic event was characterized by altered mental or physical status, requiring the 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 = 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=466 Participants Participants received 500 U/mL insulin efsitora alfa administered SC QW over a 52-week treatment period, followed by a 5-week safety follow-up period.	100 U/mL - Insulin Degludec n=462 Participants Participants received 100 U/mL insulin degludec administered SC QD over a 52-week treatment period, followed by a 5-week safety follow-up period.
Hypoglycemia Event Rate	0.58 Events per participant-year of exposure Standard Error 0.062	0.45 Events per participant-year of exposure Standard Error 0.058

SECONDARY outcome

Timeframe: Baseline up to Week 52

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

* 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 = 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=466 Participants Participants received 500 U/mL insulin efsitora alfa administered SC QW over a 52-week treatment period, followed by a 5-week safety follow-up period.	100 U/mL - Insulin Degludec n=462 Participants Participants received 100 U/mL insulin degludec administered SC QD over a 52-week treatment period, followed by a 5-week safety follow-up period.
Nocturnal Hypoglycemia Event Rate	0.08 Events per participant-year of exposure Standard Error 0.018	0.08 Events per participant-year of exposure Standard Error 0.018

SECONDARY outcome

Timeframe: Baseline, Week 26, 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 were included.

Change from baseline in body weight was reported. LS mean was determined by MMRM model with Baseline + Treatment + Time + Treatment\*Time (Type III sum of squares) as variables.

Outcome measures

Outcome measures
Measure	500 U/mL - Insulin Efsitora Alfa n=465 Participants Participants received 500 U/mL insulin efsitora alfa administered SC QW over a 52-week treatment period, followed by a 5-week safety follow-up period.	100 U/mL - Insulin Degludec n=461 Participants Participants received 100 U/mL insulin degludec administered SC QD over a 52-week treatment period, followed by a 5-week safety follow-up period.
Change From Baseline in Body Weight Week 26	3.16 Kilogram (kg) Standard Error 0.158	2.66 Kilogram (kg) Standard Error 0.158
Change From Baseline in Body Weight Week 52	3.60 Kilogram (kg) Standard Error 0.158	3.54 Kilogram (kg) Standard Error 0.159

SECONDARY outcome

Timeframe: Week 8 to Week 12, Week 22 to Week 26 and Week 48 to Week 52

* Percentage of time spent in the hypoglycemia range with blood glucose \<70 mg/dL (3.9 mmol/L), as measured during the CGM session over a 24-hour period from Week 8 to Week 12, Week 22 to Week 26, and Week 48 to Week 52 was reported. * LS mean was determined using MMRM model with Baseline + HbA1c Stratum at Baseline + Country + GLP-1 RA Use at Randomization Flag + SU Use at Randomization Flag + Treatment + Time + Treatment\*Time (Type III sum of squares) as variables.

Outcome measures

Outcome measures
Measure	500 U/mL - Insulin Efsitora Alfa n=368 Participants Participants received 500 U/mL insulin efsitora alfa administered SC QW over a 52-week treatment period, followed by a 5-week safety follow-up period.	100 U/mL - Insulin Degludec n=360 Participants Participants received 100 U/mL insulin degludec administered SC QD over a 52-week treatment period, followed by a 5-week safety follow-up period.
Percentage of Time in Hypoglycemia Range With Blood Glucose <70 mg/dL (3.9 mmol/L) Week 8 to Week 12	1.06 Percentage of time Standard Error 0.101	0.93 Percentage of time Standard Error 0.103
Percentage of Time in Hypoglycemia Range With Blood Glucose <70 mg/dL (3.9 mmol/L) Week 22 to Week 26	1.55 Percentage of time Standard Error 0.137	1.25 Percentage of time Standard Error 0.137
Percentage of Time in Hypoglycemia Range With Blood Glucose <70 mg/dL (3.9 mmol/L) Week 48 to Week 52	1.49 Percentage of time Standard Error 0.150	1.19 Percentage of time Standard Error 0.152

SECONDARY outcome

Timeframe: Week 8 to Week 12, Week 22 to Week 26 and Week 48 to Week 52

* 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 8 to Week 12, Week 22 to Week 26, and Week 48 to Week 52, was reported. * LS mean was determined using MMRM model with Baseline + HbA1c Stratum at Baseline + Country + GLP-1 RA Use at Randomization Flag + SU Use at Randomization Flag + Treatment + Time + Treatment\*Time (Type III sum of squares) as variables.

Outcome measures

Outcome measures
Measure	500 U/mL - Insulin Efsitora Alfa n=368 Participants Participants received 500 U/mL insulin efsitora alfa administered SC QW over a 52-week treatment period, followed by a 5-week safety follow-up period.	100 U/mL - Insulin Degludec n=360 Participants Participants received 100 U/mL insulin degludec administered SC QD over a 52-week treatment period, followed by a 5-week safety follow-up period.
Percentage of Time in Hypoglycemia Range With Blood Glucose <54 mg/dL (3.0 mmol/L) Week 8 to Week 12	0.24 Percentage of time Standard Error 0.041	0.27 Percentage of time Standard Error 0.041
Percentage of Time in Hypoglycemia Range With Blood Glucose <54 mg/dL (3.0 mmol/L) Week 22 to Week 26	0.33 Percentage of time Standard Error 0.037	0.28 Percentage of time Standard Error 0.037
Percentage of Time in Hypoglycemia Range With Blood Glucose <54 mg/dL (3.0 mmol/L) Week 48 to Week 52	0.32 Percentage of time Standard Error 0.043	0.30 Percentage of time Standard Error 0.043

SECONDARY outcome

Timeframe: Week 8 to Week 12, Week 22 to Week 26 and Week 48 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 8 to Week 12, Week 22 to Week 26, and Week 48 to Week 52 was reported. * LS mean was determined using MMRM model with Baseline + HbA1c Stratum at Baseline + Country + GLP-1 RA Use at Randomization Flag + SU Use at Randomization Flag + Treatment + Time + Treatment\*Time (Type III sum of squares) as variables.

Outcome measures

Outcome measures
Measure	500 U/mL - Insulin Efsitora Alfa n=368 Participants Participants received 500 U/mL insulin efsitora alfa administered SC QW over a 52-week treatment period, followed by a 5-week safety follow-up period.	100 U/mL - Insulin Degludec n=360 Participants Participants received 100 U/mL insulin degludec administered SC QD over a 52-week treatment period, followed by a 5-week safety follow-up period.
Percentage of Time in Hyperglycemia Range With Blood Glucose >180 mg/dL (10.0 mmol/L) Week 22 to Week 26	28.93 Percentage of time Standard Error 0.999	29.87 Percentage of time Standard Error 1.007
Percentage of Time in Hyperglycemia Range With Blood Glucose >180 mg/dL (10.0 mmol/L) Week 8 to Week 12	31.99 Percentage of time Standard Error 0.925	32.40 Percentage of time Standard Error 0.939
Percentage of Time in Hyperglycemia Range With Blood Glucose >180 mg/dL (10.0 mmol/L) Week 48 to Week 52	29.66 Percentage of time Standard Error 1.074	33.05 Percentage of time Standard Error 1.086

SECONDARY outcome

Timeframe: Baseline, Week 26, 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 TRIM-D is a participant-reported measure designed to assess the impact of diabetes treatment on individuals' functioning and well-being across different diabetes treatments. The questionnaire includes 28 items grouped into 5 sub-domains: treatment burden, daily life, diabetes management, compliance, and psychological health. Each item is assessed on a 5-point scale, with higher scores indicating better health status. All items were summed to obtain a total raw score, which was transformed to a scale of 0 to 100 to obtain a total score. The total score range is 0-100, with a higher total score indicating better overall health and well-being, while a lower total score indicates worse health or well-being. * LS mean was determined using MMRM model with Baseline + Country + HbA1c Stratum at Baseline + GLP-1 RA Use at Randomization Flag + SU Use at Randomization Flag + Treatment + Time + Treatment\*Time (Type III sum of squares) as variables.

Outcome measures

Outcome measures
Measure	500 U/mL - Insulin Efsitora Alfa n=444 Participants Participants received 500 U/mL insulin efsitora alfa administered SC QW over a 52-week treatment period, followed by a 5-week safety follow-up period.	100 U/mL - Insulin Degludec n=445 Participants Participants received 100 U/mL insulin degludec administered SC QD over a 52-week treatment period, followed by a 5-week safety follow-up period.
Change From Baseline in Treatment-Related Impact Measures for Diabetes (TRIM-D) -Total Score at Week 26 and Week 52 Week 26	8.84 score on a scale Standard Error 0.507	7.18 score on a scale Standard Error 0.507
Change From Baseline in Treatment-Related Impact Measures for Diabetes (TRIM-D) -Total Score at Week 26 and Week 52 Week 52	8.82 score on a scale Standard Error 0.519	6.81 score on a scale Standard Error 0.517

SECONDARY outcome

Timeframe: Baseline, Week 26, Week 52

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. Each domain is scored individually, and information from these 8 domains is further aggregated into 2 health component summary scores, the Physical Component Summary and Mental Component Summary. 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.

Outcome measures

Outcome measures
Measure	500 U/mL - Insulin Efsitora Alfa n=431 Participants Participants received 500 U/mL insulin efsitora alfa administered SC QW over a 52-week treatment period, followed by a 5-week safety follow-up period.	100 U/mL - Insulin Degludec n=434 Participants Participants received 100 U/mL insulin degludec administered SC QD over a 52-week treatment period, followed by a 5-week safety follow-up period.
Change From Baseline in Short Form-36 Health Survey Version 2 (SF-36v2) Acute Form (Physical-Component and Mental-Component) Scores at Week 26 and Week 52 Physical Component Score at Week 26	0.29 T-score Standard Error 0.344	0.49 T-score Standard Error 0.345
Change From Baseline in Short Form-36 Health Survey Version 2 (SF-36v2) Acute Form (Physical-Component and Mental-Component) Scores at Week 26 and Week 52 Mental Component Score at Week 26	0.018 T-score Standard Error 0.380	0.34 T-score Standard Error 0.381
Change From Baseline in Short Form-36 Health Survey Version 2 (SF-36v2) Acute Form (Physical-Component and Mental-Component) Scores at Week 26 and Week 52 Physical Component Score at Week 52	0.027 T-score Standard Error 0.349	-0.14 T-score Standard Error 0.351
Change From Baseline in Short Form-36 Health Survey Version 2 (SF-36v2) Acute Form (Physical-Component and Mental-Component) Scores at Week 26 and Week 52 Mental Component Score at Week 52	0.014 T-score Standard Error 0.386	0.25 T-score Standard Error 0.389

SECONDARY outcome

Timeframe: Baseline, Week 26, Week 52

The EQ-5D-5L is a multidimensional, health-related, quality-of-life instrument. It includes 5 dimensions of health (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) that are assessed at 5 levels of response (no problems, slight problems, moderate problems, severe problems, and unable to perform or extreme problems). The scores in the 5 dimensions were summarized into a health state index score. A single health-state index value was derived, which ranges from less than 0 (health state equivalent to death, negative values are valued as worse than death) to 1 (perfect health). The EQ VAS rates the participants' perceived health from 0 (the worst imaginable health) to 100 (the best imaginable health). This score provides a composite picture of the respondent's health status.

Outcome measures

Outcome measures
Measure	500 U/mL - Insulin Efsitora Alfa n=430 Participants Participants received 500 U/mL insulin efsitora alfa administered SC QW over a 52-week treatment period, followed by a 5-week safety follow-up period.	100 U/mL - Insulin Degludec n=434 Participants Participants received 100 U/mL insulin degludec administered SC QD over a 52-week treatment period, followed by a 5-week safety follow-up period.
Change From Baseline in EuroQuality of Life (EuroQol) - 5 Dimensions-5 Levels (EQ-5D-5L) Health State Index and EQ Visual Analog Scale (VAS) Scores at Week 26 and Week 52 EQ-5D-5L Health State Index Score at Week 26	-0.018 Score on a scale Standard Error 0.0078	-0.004 Score on a scale Standard Error 0.0078
Change From Baseline in EuroQuality of Life (EuroQol) - 5 Dimensions-5 Levels (EQ-5D-5L) Health State Index and EQ Visual Analog Scale (VAS) Scores at Week 26 and Week 52 EQ VAS Score at Week 26	1.07 Score on a scale Standard Error 0.701	2.18 Score on a scale Standard Error 0.699
Change From Baseline in EuroQuality of Life (EuroQol) - 5 Dimensions-5 Levels (EQ-5D-5L) Health State Index and EQ Visual Analog Scale (VAS) Scores at Week 26 and Week 52 EQ-5D-5L Health State Index Score at Week 52	-0.018 Score on a scale Standard Error 0.0077	-0.008 Score on a scale Standard Error 0.0077
Change From Baseline in EuroQuality of Life (EuroQol) - 5 Dimensions-5 Levels (EQ-5D-5L) Health State Index and EQ Visual Analog Scale (VAS) Scores at Week 26 and Week 52 EQ VAS Score at Week 52	1.56 Score on a scale Standard Error 0.733	1.91 Score on a scale Standard Error 0.739

Adverse Events

500 U/mL - Insulin Efsitora Alfa

Serious events: 41 serious events

Other events: 195 other events

Deaths: 2 deaths

100 U/mL - Insulin Degludec

Serious events: 38 serious events

Other events: 224 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	500 U/mL - Insulin Efsitora Alfa n=466 participants at risk Participants received 500 U/mL insulin efsitora alfa administered SC QW over a 52-week treatment period, followed by a 5-week safety follow-up period.	100 U/mL - Insulin Degludec n=462 participants at risk Participants received 100 U/mL insulin degludec administered SC QD over a 52-week treatment period, followed by a 5-week safety follow-up period.
Gastrointestinal disorders Diarrhoea	6.7% 31/466 • Number of events 36 • Baseline to end of follow-up (up to 57 weeks) * All randomized participants who received at least one dose of study drug. Participants were analyzed based on the actual treatment they received. * Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	6.9% 32/462 • Number of events 48 • Baseline to end of follow-up (up to 57 weeks) * All randomized participants who received at least one dose of study drug. Participants were analyzed based on the actual treatment they received. * Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Gastrointestinal disorders Nausea	5.6% 26/466 • Number of events 27 • Baseline to end of follow-up (up to 57 weeks) * All randomized participants who received at least one dose of study drug. Participants were analyzed based on the actual treatment they received. * Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	5.6% 26/462 • Number of events 29 • Baseline to end of follow-up (up to 57 weeks) * All randomized participants who received at least one dose of study drug. Participants were analyzed based on the actual treatment they received. * Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Infections and infestations Covid-19	7.9% 37/466 • Number of events 38 • Baseline to end of follow-up (up to 57 weeks) * All randomized participants who received at least one dose of study drug. Participants were analyzed based on the actual treatment they received. * Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	11.0% 51/462 • Number of events 51 • Baseline to end of follow-up (up to 57 weeks) * All randomized participants who received at least one dose of study drug. Participants were analyzed based on the actual treatment they received. * Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Infections and infestations Influenza	3.9% 18/466 • Number of events 22 • Baseline to end of follow-up (up to 57 weeks) * All randomized participants who received at least one dose of study drug. Participants were analyzed based on the actual treatment they received. * Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	5.6% 26/462 • Number of events 31 • Baseline to end of follow-up (up to 57 weeks) * All randomized participants who received at least one dose of study drug. Participants were analyzed based on the actual treatment they received. * Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Infections and infestations Nasopharyngitis	9.2% 43/466 • Number of events 50 • Baseline to end of follow-up (up to 57 weeks) * All randomized participants who received at least one dose of study drug. Participants were analyzed based on the actual treatment they received. * Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	8.9% 41/462 • Number of events 50 • Baseline to end of follow-up (up to 57 weeks) * All randomized participants who received at least one dose of study drug. Participants were analyzed based on the actual treatment they received. * Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Infections and infestations Upper respiratory tract infection	7.9% 37/466 • Number of events 52 • Baseline to end of follow-up (up to 57 weeks) * All randomized participants who received at least one dose of study drug. Participants were analyzed based on the actual treatment they received. * Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	10.0% 46/462 • Number of events 63 • Baseline to end of follow-up (up to 57 weeks) * All randomized participants who received at least one dose of study drug. Participants were analyzed based on the actual treatment they received. * Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Infections and infestations Urinary tract infection	3.6% 17/466 • Number of events 20 • Baseline to end of follow-up (up to 57 weeks) * All randomized participants who received at least one dose of study drug. Participants were analyzed based on the actual treatment they received. * Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	6.3% 29/462 • Number of events 35 • Baseline to end of follow-up (up to 57 weeks) * All randomized participants who received at least one dose of study drug. Participants were analyzed based on the actual treatment they received. * Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Injury, poisoning and procedural complications Drug titration error	7.1% 33/466 • Number of events 58 • Baseline to end of follow-up (up to 57 weeks) * All randomized participants who received at least one dose of study drug. Participants were analyzed based on the actual treatment they received. * Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	11.9% 55/462 • Number of events 86 • Baseline to end of follow-up (up to 57 weeks) * All randomized participants who received at least one dose of study drug. Participants were analyzed based on the actual treatment they received. * Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Investigations Weight increased	6.0% 28/466 • Number of events 30 • Baseline to end of follow-up (up to 57 weeks) * All randomized participants who received at least one dose of study drug. Participants were analyzed based on the actual treatment they received. * Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	4.3% 20/462 • Number of events 20 • Baseline to end of follow-up (up to 57 weeks) * All randomized participants who received at least one dose of study drug. Participants were analyzed based on the actual treatment they received. * Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Nervous system disorders Headache	4.5% 21/466 • Number of events 30 • Baseline to end of follow-up (up to 57 weeks) * All randomized participants who received at least one dose of study drug. Participants were analyzed based on the actual treatment they received. * Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	6.1% 28/462 • Number of events 47 • Baseline to end of follow-up (up to 57 weeks) * All randomized participants who received at least one dose of study drug. Participants were analyzed based on the actual treatment they received. * Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60