A Study of Insulin Efsitora Alfa (LY3209590) Compared to Glargine in Adult Participants With Type 2 Diabetes Who Are Starting Basal Insulin for the First Time (QWINT-1)

Phase 3

Completed

Conditions: T2D
Type 2 Diabetes

Interventions: Drug: Insulin Efsitora Alfa
Drug: Insulin Glargine

Registration Number: NCT05662332

Lead Sponsor: Eli Lilly and Company

Brief Summary: The main purpose of this study is to determine the efficacy and safety of insulin efsitora alfa (LY3209590) administered weekly using a fixed dose escalation compared to insulin glargine in adults with type 2 diabetes (T2D) who are starting basal insulin therapy for the first time.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 795

Inclusion Criteria

Have a diagnosis of T2D according to the World Health Organization criteria.
Have an HbA1c of 7.0% to 10.0%, 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.
Are insulin naive

Exceptions:

short-term insulin treatment for a maximum of 14 days, prior to screening, and
prior insulin treatment for gestational diabetes.

Exclusion Criteria

Have a diagnosis of type 1 diabetes (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%.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Insulin Efsitora Alfa	Insulin Efsitora Alfa	Participants received Insulin Efsitora Alfa (insulin efsitora; 500 U/ml) administered subcutaneously (SC) once weekly (QW) for 52 weeks, with titration using fixed-doses 100 U, 150 U, 250 U, and 400 U.
Insulin Glargine	Insulin Glargine	Participants received insulin glargine (100 U/ml) administered SC once daily (QD) for 52 weeks with titration by standard sliding-scale dose adjustments.

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Hemoglobin A1c (HbA1c) [Noninferiority Analysis]	Baseline, Week 52	HbA1c is the glycated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over the last 2-3 months. Least Squares (LS) Mean was determined using ANCOVA model with Baseline + Country + GLP-1 RA Use at Randomization Flag + Treatment (Type III sum of squares) as variables. Missing data at Week 52 were imputed by return-to-baseline multiple imputation approach.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in HbA1c [Superiority]	Baseline, Week 52	HbA1c is the glycated 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 + GLP-1 RA Use at Randomization Flag + Treatment (Type III sum of squares) as variables. Missing data at Week 52 were imputed by return-to-baseline multiple imputation approach.
Change From Baseline in Fasting Glucose	Baseline, Week 52	Change from baseline in fasting blood glucose measured by self-monitoring blood glucose (SMBG). LS mean was determined using ANCOVA model with Variable = Baseline + Country + GLP-1 RA Use at Baseline + Hemoglobin A1c Stratum at Baseline + Treatment (Type III sum of squares).
Basal Insulin Dose at Week 52	Week 52	The insulin dose was recorded daily or weekly in an electronic diary. The average weekly basal insulin dose at Week 52 was reported. LS mean was determined using MMRM model with Baseline + Hemoglobin A1c Stratum at Baseline + Country + GLP-1 RA use at Randomization + Treatment + Time + Treatment\*Time (Type III sum of squares) as variables.
Rate Per Year of Hypoglycemia Events	Baseline up to Week 52	Rate of Composite Level 2 and 3 Hypoglycemia Events were reported. Hypoglycemia with glucose \<54 mg/dL (Level 2) or Severe Hypoglycemia confirmed by the investigator to be an event that required assistance for treatment (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 model using Number of episodes = Hemoglobin A1c at Baseline (%) + Treatment, with log (exposure in days/365.25) as an offset variable.
Percentage of Participants With Hypoglycemia Events (Incidence)	Week 52	Incidence of hypoglycemic episodes is defined as 100 multiplied by the number of participants experiencing a hypoglycemic episode divided by the number of participants exposed to the study drug. Incidence of Composite Level 2 and 3 Hypoglycemia Events was reported. Hypoglycemic episodes are defined as an event that is associated with reported signs and symptoms of hypoglycemia with glucose \<54 mg/dL (Level 2) or severe hypoglycemia confirmed by the investigator to be an event that required assistance for treatment (Level 3). 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.
Rate Per Year of Nocturnal Hypoglycemia Events	Baseline up to Week 52	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 52. 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 Participants With Nocturnal Hypoglycemia Events (Incidence)	Week 52	Incidence of nocturnal hypoglycemic episodes is defined as 100 multiplied by the number of participants experiencing a hypoglycemic episode divided by the number of participants exposed to the study drug. Nocturnal hypoglycemia is defined as any hypoglycemic event that occurs between bedtime and waking. 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 52..
Change From Baseline in Body Weight	Baseline, Week 52	Change from baseline in body weight was reported. LS mean was determined using ANCOVA model with Variable = Baseline + Country + GLP-1 RA Use at Baseline + Hemoglobin A1c Stratum at Baseline + Treatment (Type III sum of squares).
Change From Baseline in Treatment-Related Impact Measure - Diabetes (TRIM-D) Total Score	Baseline, Week 52	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. The TRIM-D questionnaire consists of 5 sub-domains. Treatment Burden (6 items) Daily Life (5 items) Diabetes Management (5 items), Compliance (4 items), and Psychological Health (8 items), where each question is scored on a 1-5-point scale with a higher score indicating a better health state (less negative impact). Mean TRIM-D individual sub-domain scores and total scores are later transformed to a 0-100 scale for analysis. LS mean change in scores from baseline to 52 weeks for total score are presented here. LS mean was determined using MMRM model with BASELINE + Hemoglobin A1c Stratum at Baseline + Country + GLP-1 RA. Use at Randomization + Treatment + Time + Treatment\*Time(Type III sum of squares) as variables.
Change From Baseline in Diabetes Treatment Satisfaction Questionnaire - Change Version (DTSQ-c)	Baseline, Week 52	The DTSQ-c is a validated, patient-reported questionnaire designed to assess perceived changes in satisfaction with diabetes treatment over time. It is especially useful in clinical trials comparing a new treatment to a previous one. The DTSQ-c includes 8 items, each scored on a 7-point Likert scale ranging from -3 (Much less satisfied) to +3 (Much more satisfied). A score of 0 indicates no change in perception. This outcome reports three domains: (1) Perceived frequency of hypoglycaemia - lower scores reflect fewer perceived episodes; (2) Perceived frequency of hyperglycaemia - lower scores reflect fewer perceived episodes; (3) Treatment satisfaction -Aggregated score from the remaining 6 items assessing satisfaction with treatment, convenience, flexibility, understanding, and willingness to continue. A higher scores indicating greater improvement in satisfaction. Total score range: -18 to +18.
Percentage of Participants Reporting Treatment Experience Using the Simplicity of Diabetes Treatment Questionnaire (SIM-Q) Single Medication Status Version	Week 52	The SIM-Q is a brief 10-item measure developed to assess the simplicity and complexity of treatment for T2D. This version of the instrument assesses the simplicity and complexity of a single medication. Only the last 2 questions/items of the SIM-Q were completed by the study participants: 1. "How simple or complex is your medication treatment for diabetes?" 2. "Overall, how simple or complex is it to manage your diabetes, including medication, checking your blood glucose levels, diet, and any other aspects of diabetes treatment?" Participants were asked to provide responses to the study intervention at Week 52. Each item is scored on a 5-point scale ranging from "Very complex" to "Very simple." Higher scores indicate a more favorable (simpler) treatment experience.
Change From Baseline in Diabetes Injection Device Experience Questionnaire (DID-EQ) in Device Characteristics	Baseline, Week 52	DID-EQ is a validated, self-administered, 10-item PRO instrument designed to assess participants' perceptions of diabetes injection delivery systems.This outcome measure reports only the Device Characteristics Subscale, which includes Items 1 through 7. These items evaluate specific features of injection devices such as: * Ease of preparation * Comfort during injection * Portability * Discreetness * Confidence in dose delivery * Ease of learning to use * Satisfaction with device features Each item is rated on a 4-point Likert scale: Strongly Disagree, Disagree, Agree, Strongly Agree. Responses are transformed to a 0-100 scale, where 0 represents most negative perception and 100 represents the most positive perception.Higher scores indicate more favorable perceptions of the injection device. LS Mean determined using ANCOVA model with Country + GLP-1 RA Use at Randomization + HbA1c Stratum at Baseline + Treatment + Time + Treatment\*Time (Type III sum of squares) as variables.
Percentage of Participants in Treatment Experience in Diabetes Injection Device Experience Questionnaire (DID-EQ) (3-Global Items)	Week 52	The DID-EQ is a validated, self-administered, 10-item PRO instrument designed to assess participants' perceptions of diabetes injection delivery systems. This outcome measure specifically reports the summary of DID-EQ scores for the 3 global items: * Item 8: Overall satisfaction with the injection device * Item 9: Ease of use of the injection device * Item 10: Convenience of the injection device Each item is rated on a 4-point Likert scale: * Strongly Disagree * Disagree * Agree * Strongly Agree Responses are transformed to a 0-100 scale, where: * 0 = Most negative perception * 100 = Most positive perception Higher scores indicate more favorable perceptions of the injection device's global characteristics.

Trial Locations

Locations (70): Cahaba Research
🇺🇸
Birmingham, Alabama, United States
Syed Research Consultants Llc
🇺🇸
Sheffield, Alabama, United States
AMCR Institute
🇺🇸
Escondido, California, United States
Velocity Clinical Research, Gardena
🇺🇸
Gardena, California, United States
National Research Institute - Huntington Park
🇺🇸
Huntington Park, California, United States
National Research Institute - Wilshire
🇺🇸
Los Angeles, California, United States
Diabetes Associates Medical Group
🇺🇸
Orange, California, United States
Encompass Clinical Research
🇺🇸
Spring Valley, California, United States
Millennium Clinical Trials
🇺🇸
Thousand Oaks, California, United States
University Clinical Investigators, Inc.
🇺🇸
Tustin, California, United States
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Cahaba Research
🇺🇸Birmingham, Alabama, United States