A Study of Insulin Efsitora Alfa (LY3209590) Compared With Insulin Degludec in Participants With Type 2 Diabetes Currently Treated With Basal Insulin

Study Overview
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Brief Summary
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The reason for this study is to see if the study drug insulin efsitora alfa (LY3209590) is safe and effective in participants with Type 2 diabetes that have already been treated with basal insulin. The study consists of a 3-week screening/lead-in period, a 78-week treatment period and a 5-week safety follow-up period. The study will last up to 86 weeks.

Official Title
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A Phase 3, Multicenter, Randomized, Parallel-Design, Open-Label Trial to Evaluate the Efficacy and Safety of LY3209590 Compared With Insulin Degludec in Participants With Type 2 Diabetes Currently Treated With Basal Insulin (QWINT-3)

Conditions
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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 been diagnosed with Type 2 diabetes according to the World Health Organization (WHO) criteria treated with basal insulin Are receiving ≥10 units of basal insulin per day and ≤110 units per day at screening Have HbA1c value of 6.5% - 10% inclusive, at screening Have a Body mass index (BMI) less than or equal to 45 kilogram/square meter (kg/m²) Have been treated with one of the following stable insulin regimens at least 90 days prior to screening: once daily U100 or U200 of insulin degludec once daily U100 or U300 of insulin glargine once or twice daily U100 of insulin detemir, or once or twice daily human insulin NPH acceptable non insulin glucose lowering therapies may include 0 to up to 3 of the following: dipeptidyl peptidase (DPP-4) IV inhibitors SGLT2 inhibitors metformin alphaglucosidase inhibitors or, Glucagon-Like Peptide-1 (GLP-1) receptor agonists Participants must be willing to stay on stable dose throughout the study Exclusion Criteria: Have Type 1 diabetes mellitus Have acute or chronic hepatitis, cirrhosis, or obvious clinical signs or symptoms of any other liver disease, except Nonalcoholic Fatty Liver Disease (NAFLD) Estimated glomerular filtration rate (eGFR) <20 milliliters/minute/1.73 square meter (m²) Have active or untreated malignancy Are pregnant Have a significant weight gain or loss the past 3 months Have received anytime in the past 6 months, any of the following insulin therapies: prandial insulin insulin mixtures inhaled insulin U-500 insulin, or continuous subcutaneous insulin infusion therapy Have had any of New York Heart Association Class IV heart failure or any of the following CV conditions in the past 3 months: acute myocardial infarctions cerebrovascular accident (stroke), or coronary bypass surgery Gastrointestinal: have undergone gastric bypass (bariatric) surgery, restrictive bariatric surgery (Lap-Band) or sleeve gastrectomy within 1 year prior to screening

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 be given insulin efsitora alfa subcutaneously (SC). | Drug: Insulin Efsitora Alfa<br>* Administered SC<br>* Other names: LY3209590 and Basal Insulin-FC;|
| Active Comparator: Insulin Degludec<br>Participants with be given insulin degludec SC. | 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 compared to insulin degludec on glycemic control in participants with type 2 diabetes currently on basal insulin. | Baseline, Week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nocturnal Hypoglycemia Event Rate | The event rate of participant-reported clinically significant nocturnal hypoglycemia (<54 milligram/deciliter (mg/dL) or severe) measured during treatment phase up to Week 78. | Baseline to Week 78 | 
| Time in Range | Time in glucose range between 70 and 180 mg/dL inclusive measured by continued glucose monitoring (CGM) during a 4-week CGM session. | Week 22 to Week 26 | 
| Change from Baseline in Fasting Glucose | Fasting glucose measured by Self-Monitoring of Blood Glucose (SMBG). | Baseline, Week 26 | 
| Weekly Insulin dose | The weekly insulin dose calculated based on participant entry of daily or weekly insulin dose in an electronic diary. | Week 26 | 
| Level 2 or Level 3 Nocturnal Hypoglycemia Event Rate | The event rate of participant-reported clinically significant nocturnal hypoglycemia (<54 milligram/deciliter (mg/dL) or severe) measured during treatment phase. | Baseline to Week 78 | 
| Change from Baseline in Body Weight | Change from baseline in body weight | Baseline, Week 78 | 
| Time in Hypoglycemia Range | Time in hypoglycemia range defined as time in hypoglycemia with glucose <54 mg/dL measured during the CGM session. | Week 22 to Week 26 | 
| Time in Hyperglycemia Range | Time in hyperglycemia range defined as time in hyperglycemia with glucose >180 mg/dL measured during the CGM session. | Week 22 to Week 26 | 
| Change from Baseline in Treatment-Related Impact Measure - Diabetes (TRIM-D) | TRIM-D assesses the impact of diabetes treatment on participants' functioning and well-being across available diabetes treatment. | Baseline, Week 26 | 
| Change from Baseline in Diabetes Treatment Satisfaction Questionnaire-Status Version (DTSQ) | DTSQ assesses the overall treatment satisfaction and perceived frequency of hyperglycemia and hypoglycemia. | Baseline, Week 26 | 
| Change from Baseline in Diabetes Treatment Satisfaction Questionnaire-Status Version (DTSQ) | DTSQ assesses the overall treatment satisfaction and perceived frequency of hyperglycemia and hypoglycemia. | Baseline, Week 78 |