A Study of Insulin Efsitora Alfa (LY3209590) as a Weekly Basal Insulin Compared to Insulin Glargine in Adult Participants With Type 2 Diabetes on Multiple Daily Injections

Study Overview
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Brief Summary
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The reason for this study is to evaluate if the once-weekly study drug insulin efsitora alfa (LY3209590) is safe and effective compared with daily insulin glargine in participants with Type 2 diabetes (T2D) that have already been treated with basal insulin and at least 2 injections per day of prandial insulin. The study consists of a 3-week screening/lead-in period, a 26-week treatment period and a 5-week safety follow-up period. The study will last up to 34 weeks.

Official Title
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A Phase 3, Parallel-Design, Open-Label, Randomized Controlled Study to Evaluate the Efficacy and Safety of LY3209590 as a Weekly Basal Insulin Compared to Insulin Glargine in Adults With Type 2 Diabetes on Multiple Daily Injections

Conditions
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Type 2 Diabetes, Type 2 Diabetes Treated With Insulin

Intervention / Treatment
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* Drug: Insulin Efsitora Alfa
* Drug: Insulin Lispro (U100)
* Drug: Insulin Glargine (U100)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have a diagnosis of T2D according to the world health organization (WHO) criteria, currently treated with basal insulin and at least 2 injections of prandial insulin per day. Are receiving ≥10 units of total basal insulin per day at screening. Are receiving ≤2 units/kilogram/day of total daily insulin at screening Have an HbA1c value of 7.0% to 10%, inclusive, as determined by the central laboratory at screening Have been treated with a stable regimen of one of the following basal insulins used according to local product label with or without noninsulin diabetes therapy for at least 90 days prior to screening once daily U-100 or U-200 insulin degludec once daily U-100 or U-300 insulin glargine once or twice daily U-100 insulin detemir or once or twice daily human insulin Neutral Protamine Hagedorn Have been treated with at least twice daily dosing of one of the following insulins used according to local product label for at least 90 days prior to screening. One dose of prandial insulin must occur at the evening meal. Insulin lispro-aabc Insulin lispro (U-100 and U-200)s, IN], U-100 or U200) Insulin aspart (U-100) Insulin glulisine (U-100), or Regular insulin (U-100) Acceptable noninsulin diabetes therapies may include 0 to up to 3 of the following with a stable dose for at least 90 days prior to screening dipeptidyl peptidase IV inhibitors sodium-glucose co-transporter-2 inhibitors biguanides (for example, metformin), or glucagon-like peptide-1 receptor agonists Note: All noninsulin diabetes therapies must be used in accordance with the corresponding local product label at the time of screening, and participants should be willing to continue stable dosing throughout the study Have a body mass index ≤45 kilogram/square meter (kg/m²) Exclusion Criteria: Have a diagnosis of type 1 diabetes mellitus or latent autoimmune diabetes, or specific type of diabetes other than T2D (for example, monogenic diabetes, diseases of the exocrine pancreas, drug-induced or chemical-induced diabetes). Are currently receiving any of the following insulin therapies anytime in the past 90 days: insulin mixtures insulin human, inhalation powder, or continuous subcutaneous insulin infusion therapy, or regular insulin U-500 Have a history of greater than 1 episode of ketoacidosis or hyperosmolar state/coma requiring hospitalization in the 6 months prior to screening Have had any episodes of severe hypoglycemia, defined as requiring assistance due to neurologically disabling hypoglycemia, within the 6 months prior to screening Have hypoglycemia unawareness in the opinion of the investigator Anticipate making changes in personal CGM or flash glucose monitoring (FGM) use (for example, initiation, stopping, or changing device) during the study. Have had New York Heart Association Class IV heart failure or any of the following cardiovascular conditions in the past 3 months prior to screening: acute myocardial infarction, cerebrovascular accident (stroke), or coronary bypass surgery. Have undergone gastric bypass (bariatric) surgery, restrictive bariatric surgery, or sleeve gastrectomy within 1 year prior to screening

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 + Insulin Lispro<br>Participants will be given insulin efsitora alfa by subcutaneous (SC) injection along with insulin lispro | Drug: Insulin Efsitora Alfa<br>* Administered SC<br>* Other names: LY3209590 and Basal Insulin-FC;Drug: Insulin Lispro (U100)<br>* Administered SC<br>* Other names: Humalog;|
| Active Comparator: Insulin Glargine + Insulin Lispro<br>Participants will be given insulin glargine by SC injection along with insulin lispro | Drug: Insulin Lispro (U100)<br>* Administered SC<br>* Other names: Humalog;Drug: Insulin Glargine (U100)<br>* Administered SC<br>* Other names: Basaglar;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in HbA1c | Change from Baseline in HbA1c of insulin efsitora alfa compared to insulin glargine on glycemic control in adult participants with type 2 diabetes on multiple daily injections. | Baseline, Week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving HbA1c <7% without Nocturnal Hypoglycemia | Percentage of participants achieving HbA1c <7% without nocturnal hypoglycemia milligram/deciliter (mg/dL) [3.0 millimole/Liter (mmol/L) or severe] during treatment phase up to week 26. | Week 26 | 
| Nocturnal Hypoglycemia Event Rate | The event rate of participant-reported clinically significant nocturnal hypoglycemia <54 mg/dL (3.0 mmol/L) or severe) measured during treatment phase up to week 26. | Baseline to Week 26 | 
| Change from Baseline in Fasting Glucose | Change from baseline in fasting glucose measured by small monitoring blood glucose (SMBG) | Baseline, Week 26 | 
| Time in Glucose Range | Time in glucose range between 70 and 180 mg/dL (3.9 and 10.0 mmol/L), inclusive measured during the continuous glucose monitoring (CGM) session | Week 22 to Week 26 | 
| Time in Hypoglycemia Range | Time in hypoglycemia range with glucose <54 mg/dL (3.0 mmol/L), measured by CGM | Week 22 to Week 26 | 
| Time in Hyperglycemia Range | Time in hyperglycemia range with glucose >180 mg/dL (10.0 mmol/L), measured by CGM | Week 22 to Week 26 | 
| Glucose Variability | Glucose variability measured during the CGM session | Week 22 to Week 26 | 
| Basal Insulin Dose |  | Week 26 | 
| Bolus Insulin Dose |  | Week 26 | 
| Total Insulin Dose |  | Week 26 | 
| Basal Insulin Dose to Total Insulin Dose Ratio |  | Week 26 | 
| Hypoglycemia Event Rate | Incidence and rate of composite of level 2 and 3 hypoglycemia event | Baseline to Week 26 | 
| Change from Baseline in Body Weight |  | Baseline, Week 26 | 
| Treatment Experience for Diabetes Injection Device at Week 26 - Experience Questionnaire (DID-EQ) | The DID-EQ is a self-administered 10-item questionnaire designed to assess participants' perceptions of diabetes injection delivery systems for T2D. Each item is rated on a four-point Likert scale. Scores are transformed and range from 0 to 100. Higher scores indicate more positive perceptions of injection device characteristics. | Week 26 |