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

Phase 3

Completed

Conditions: Type 2 Diabetes

Interventions: Drug: Insulin Efsitora Alfa
Drug: Insulin Degludec

Registration Number: NCT05275400

Lead Sponsor: Eli Lilly and Company

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 986

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
500 U/mL - Insulin Efsitora	Insulin Efsitora Alfa	Participants received 500 units per milliliter (U/mL) Insulin Efsitora Alfa (insulin efsitora) administered subcutaneously (SC) once weekly (QW).
100 U/mL - Insulin Degludec	Insulin Degludec	Participants received 100 U/mL insulin degludec administered SC once daily (QD).

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Hemoglobin A1c (HbA1c) [Noninferiority]	Baseline, Week 26	HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time. Least Squares (LS) Mean was determined using ANCOVA model with Baseline + Country + Type of Basal Insulin used at Baseline + Treatment (Type III sum of squares) as variables. Missing data at Week 26 were imputed by return-to-baseline multiple imputation approach.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Hemoglobin A1c (HbA1c) [Superiority]	Baseline, Week 26	HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time. Least Squares (LS) Mean was determined using ANCOVA model with Baseline + Country + Type of Basal Insulin used at Baseline + Treatment (Type III sum of squares) as variables. Missing data at Week 26 were imputed by return-to-baseline multiple imputation approach.
Nocturnal Hypoglycemia Event Rate	Baseline up to Week 78	The event rate of participant-reported clinically significant glucose \<54 mg/dL (3.0 mmol/L) or severe nocturnal hypoglycemia that occurs at night and presumably during sleep between midnight and 6:00 AM), measured during treatment period up to week 78. Group mean is reported here. Group mean is determined by Negative Binomial Model using Number of episodes = Hemoglobin A1c at Baseline (%) + Treatment, with log (exposure in days/365.25) as an offset variable.
Percentage of Time in Glucose Range Between 70 and 180 mg/dL (3.9 and 10.0 mmol/L)	Week 22 to Week 26	Percentage of time in glucose range between 70 and 180 mg/dL (3.9 and 10.0 millimoles per liter (mmol/L)) inclusive measured by continued glucose monitoring (CGM) during CGM session prior to week 26. LS Mean was calculated using ANCOVA model with Baseline + Country + Hemoglobin A1c Stratum at Baseline + Type of Basal Insulin used at Baseline + Treatment (Type III sum of squares) as variables. Missing data during CGM session prior to Week 26 were imputed by return-to-baseline multiple imputation approach.
Change From Baseline in Fasting Glucose	Baseline, Week 26	Fasting glucose measured by Self-Monitoring of Blood Glucose (SMBG). LS Mean was determined using ANCOVA model with Baseline + Country + Type of Basal Insulin at Baseline + Baseline HbA1C Stratum (%) + Treatment (Type III sum of squares) as variables. Missing data at baseline are imputed with multiple imputation under assumption of missing at random. Missing data at Week 26 are imputed by return-to-baseline multiple imputation approach.
Weekly Insulin Dose at Week 26	Week 26	The average weekly insulin dose at Week 26 was reported. LS Mean was determined by mixed model repeated measures (MMRM) model using BASELINE + Country + Type of Basal Insulin at Baseline + Baseline HbA1C Stratum (%) + Treatment + Time + Treatment\*Time (Type III sum of squares) as variables. Variance-covariance structure was set as compound symmetry.
Hypoglycemia Event Rate	Baseline up to Week 78	Patient reported events of hypoglycemia - Hypoglycemia with glucose \<54 mg/dL (Level 2) or Severe Hypoglycemia (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 method using Hemoglobin A1c at Baseline (%) + Treatment, with log (exposure in days/365.25) as variables.
Change From Baseline in Body Weight	Baseline, Week 78	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.
Percentage of Time in Hypoglycemia Range	Week 22 to Week 26	Percentage of time in hypoglycemia range with glucose \<54 mg/dL (3.0 mmol/L) measured during CGM from 22-26 weeks. LS Mean was determined using ANCOVA model using Baseline + Country + Hemoglobin A1c Stratum at Baseline + Type of Basal Insulin used at Baseline + Treatment (Type III sum of squares) as variables. Missing data at baseline were imputed with multiple imputation under assumption of missing at random. Missing data at Week 22-26 were imputed by return-to-baseline multiple imputation approach.
Percentage of Time in Hyperglycemia Range	Week 22 to Week 26	Percentage of time in hyperglycemia range with glucose \>180 mg/dL (10.0 mmol/L) measured during the CGM session from 22-26 weeks. LS Mean was determined using ANCOVA model using Baseline + Country + Hemoglobin A1c Stratum at Baseline + Type of Basal Insulin used at Baseline + Treatment (Type III sum of squares) as variables. Missing data at baseline were imputed with multiple imputation under assumption of missing at random. Missing data at Week 22-26 were imputed by return-to-baseline multiple imputation approach.
Change From Baseline in Treatment-Related Impact Measure - Diabetes (TRIM-D)	Baseline, Week 26, Week 52, Week 78	The TRIM-D is a self-administered instrument, which assesses the impact of diabetes treatment on participants' functioning and well-being across available diabetes treatments. The TRIM-D consists of 28 items each assessed on a 5-point scale. TRIM-D items assess 5 domains of impact: * Treatment Burden (6 items) * Daily Life (5 items) * Diabetes Management (5 items) * Compliance (4 items), and * Psychological Health (8 items) Items within each domain are summed to obtain a raw domain score, which is then transformed to a 0-100 scale, where higher scores indicate a greater impact on participant's functioning and well-being. LS mean was determined using MMRM model with BASELINE + Country + Type of Basal Insulin at Baseline + Baseline HbA1C Stratum (%) + Treatment + Time + Treatment\*Time (Type III sum of squares) as variables.
Diabetes Treatment Satisfaction Questionnaire-Change Version (DTSQc) - Treatment Satisfaction Score: Week 26	Week 26	DTSQc treatment satisfaction score is a 6-item questionnaire which assesses relative change in overall treatment satisfaction. The treatment satisfaction score ranges from -18 to 18, where higher the score the greater the improvement in satisfaction with treatment. The lower the score the greater the deterioration in satisfaction with treatment.
Diabetes Treatment Satisfaction Questionnaire-Change Version (DTSQc) - Treatment Satisfaction Score: Week 52	Week 52	DTSQc treatment satisfaction score is a 6-item questionnaire which assesses relative change in overall treatment satisfaction. The treatment satisfaction score ranges from -18 to 18, where higher the score the greater the improvement in satisfaction with treatment. The lower the score the greater the deterioration in satisfaction with treatment.
Diabetes Treatment Satisfaction Questionnaire-Change Version (DTSQc) - Treatment Satisfaction Score: Week 78	Week 78	DTSQc treatment satisfaction score is a 6-item questionnaire which assesses relative change in overall treatment satisfaction. The treatment satisfaction score ranges from -18 to 18, where higher the score the greater the improvement in satisfaction with treatment. The lower the score the greater the deterioration in satisfaction with treatment.

Trial Locations

Locations (127): Medical Investigations
🇺🇸
Little Rock, Arkansas, United States
John Muir Physician Network Research Center
🇺🇸
Concord, California, United States
AMCR Institute
🇺🇸
Escondido, California, United States
National Research Institute - Huntington Park
🇺🇸
Huntington Park, California, United States
Scripps Whittier Diabetes Institute
🇺🇸
La Jolla, California, United States
Diabetes Associates Medical Group
🇺🇸
Orange, California, United States
University Clinical Investigators, Inc.
🇺🇸
Tustin, California, United States
Chase Medical Research, LLC
🇺🇸
Waterbury, Connecticut, United States
Encore Medical Research
🇺🇸
Hollywood, Florida, United States
New Horizon Research Center
🇺🇸
Miami, Florida, United States
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Medical Investigations
🇺🇸Little Rock, Arkansas, United States