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

Study Overview
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Brief Summary
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The purpose of this study is to determine the effect and safety of insulin efsitora alfa (LY3209590) compared to degludec in adult participants with type 2 diabetes who are starting basal insulin for the first time. Additional participants will continue to be enrolled in a maximum extended enrollment cohort.

Official Title
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A Phase 3, Parallel-Design, Open-Label, Randomized Control Study to Evaluate the Efficacy and Safety of LY3209590 as a Weekly Basal Insulin Compared to Insulin Degludec in Insulin Naïve Adults With Type 2 Diabetes

Conditions
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Diabetes, Type 2 Diabetes

Intervention / Treatment
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* Drug: Insulin Efsitora Alfa
* Drug: Insulin Degludec


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have diagnosis of T2D according to the World Health Organization Criteria Have an HbA1c of 7.0% - 10% inclusive, at screening Are on a stable treatment of at least 1 antihyperglycemic medication, for at least 3 months prior to screening, and willing to continue the stable treatment for the duration of the study Exclusion Criteria: Have a diagnosis of T1D, latent autoimmune diabetes, or specific type of diabetes other than T2D, for example, monogenic diabetes, diseases of the exocrine pancreas, or drug induced or chemical-induced diabetes. Have a history of >1 episode of ketoacidosis or hyperosmolar state or coma requiring hospitalization within 6 months prior to screening. Have had severe hypoglycemia episodes within 6 months prior to screening. Have known hemoglobinopathy, hemolytic anemia or sickle cell anemia, or any other traits of hemoglobin abnormalities known to interfere with the measurement of HbA1c. Have had New York Heart Association Class IV heart failure or any of these cardiovascular conditions within 3 months prior to screening acute myocardial infarction cerebrovascular accident (stroke), or coronary bypass surgery. Have had gastric bypass (bariatric) surgery, restrictive bariatric surgery, for example Lap-Band, or sleeve gastrectomy within 1 year prior to screening Have had significant weight gain or loss within 3 months prior to screening, for example, ≥5%.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Insulin Efsitora Alfa<br>Participants will receive insulin efsitora alfa subcutaneously (SC) once weekly. | Drug: Insulin Efsitora Alfa<br>* Administered SC<br>* Other names: LY3209590 and Basal Insulin-FC;|
| Active Comparator: Insulin Degludec<br>Participants will receive insulin degludec SC once daily | Drug: Insulin Degludec<br>* Administered SC<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Hemoglobin A1c (HbA1c) | Change from Baseline in HbA1c of insulin efsitora alfa (LY3209590) compared to insulin degludec for the treatment of type 2 diabetes (T2D) in adults. | Baseline, Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in HbA1c | Change from Baseline in HbA1c of insulin efsitora alfa (LY3209590) compared to insulin degludec for participants using glucagon-like peptide-1 (GLP-1) receptor agonists | Baseline, Week 52 | 
| Change from Baseline in HbA1c | Change from Baseline in HbA1c of insulin efsitora alfa (LY3209590) compared to insulin degludec for participants not using GLP-1 receptor agonists | Baseline, Week 52 | 
| Time in Glucose Range | Time in glucose range between 70 and 180 milligram/deciliter inclusive, collected during the continued glucose monitoring session prior to week 52. | Week 48 to Week 52 | 
| Change from Baseline in Fasting Glucose | Change from baseline in fasting glucose measured by self-monitoring blood glucose (SMBG) | Baseline, Week 52 | 
| Weekly Insulin Dose | The weekly insulin dose calculated based on participant entry of daily or weekly insulin dose in an electronic diary. | Baseline, Week 52 | 
| Level 2 or Level 3 Nocturnal Hypoglycemia Events | The event rate of participant-reported clinically significant nocturnal hypoglycemia (<54 milligram/deciliter (mg/dL) or severe) measured during treatment phase. | Baseline to Week 52 | 
| Change from Baseline in Body Weight | Change from baseline in body weight | Baseline, Week 52 | 
| Time in hypoglycemia range with glucose <54 mg/dL | Time in hypoglycemia with glucose <54 mg/dL measurements collected during continuous glucose monitoring (CGM) sessions collected prior to Week 52 | Week 48 to Week 52 | 
| Time in Hyperglycemia range with glucose >180 mg/dL | Time in hypoglycemia with glucose >180 mg/dL measurements collected during CGM sessions collected prior to Week 52 | Week 48 to Week 52 | 
| Change from Baseline in Treatment-Related IMPACT Measures-Diabetes (TRIM-D) | TRIM-D assesses the impact of diabetes treatment on participants' functioning and well-being across available diabetes treatments. Each of the 28 items is assessed on a 5-point scale, where higher scores indicate a better health state. | Baseline, Week 52 | 
| Change from Baseline in Short Form-36 Version 2 Health Survey Acute Form (SF-36) | SF-36 v2 Health Survey Acute form is a participant self-administered measure designed to assess these 8 domains: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional, and Mental Health. Each domain is scored individually. Scoring of each domain and both summary scores, physical and mental component scores, are norm based and presented in the form of T-scores, with a mean of 50 and standard deviation of 10. Higher scores indicate better levels of function and/or better health. | Baseline, Week 52 | 
| Change from Baseline in EuroQol-5 Dimension-5 Level (EQ-5D-5L) | EQ-5D-5L assesses 5 dimensions of health mobility, self-care, usual activities, pain or discomfort, and anxiety or depression. The 5L version scores each dimension at 5 levels, no problems, slight problems, moderate problems, severe problems, and unable to perform or extreme problems. Each domain score ranges between less than 0 to 1, where negative values are valued as worse than dead, 0 is a health state equivalent to death, and 1 represents perfect health. | Baseline, Week 52 |