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 (QWINT-4)

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

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.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes; Type 2 Diabetes Treated With Insulin
• Intervention / Treatment: Drug: Insulin Lispro (U100); Drug: Insulin Glargine (U100); Drug: Insulin Efsitora Alfa

• Study Type: Interventional
• Enrollment (Actual): 730
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Ciudad Autónoma de Buenos Aires, Argentina, C1440AAD
    • CENUDIAB
  • Córdoba, Argentina, 5000
    • Instituto de Investigaciones Clínicas Córdoba
  • Santa Fe, Argentina, 3000
    • Centro de Investigaciones Clinicas del Litoral
  • Buenos Air
    • Ciudad Autonoma de Buenos Aire, Buenos Air, Argentina, C1405BUB
      • Consultorio de Investigacion Clinica EMO SRL
  • Buenos Aires
    • Caba, Buenos Aires, Argentina, C1060ABN
      • CEDIC
    • Ciudad Autónoma de Buenos Aire, Buenos Aires, Argentina, 1056
      • Centro de Investigaciones Metabólicas (CINME)
    • San Nicolas, Buenos Aires, Argentina, 2900
      • Go Centro Medico San Nicolas
  • Ciudad Autónoma De Buenos Aire
    • Caba, Ciudad Autónoma De Buenos Aire, Argentina, 1204
      • Instituto Centenario
    • Ciudad Autonoma de Buenos Aire, Ciudad Autónoma De Buenos Aire, Argentina, C1425AGC
      • Centro Medico Dra. Laura Maffei- Investigacion Clinica Aplicada
  • Ciudad Autónoma De Buenos Aires
    • Buenos Aires, Ciudad Autónoma De Buenos Aires, Argentina, C1128AAF
      • Mautalen Salud e Investigación
    • Caba, Ciudad Autónoma De Buenos Aires, Argentina, C1061AAS
      • CIPREC
  • Córdoba
    • Río Cuarto, Córdoba, Argentina, 5800
      • Instituto Medico Rio Cuarto
  • La Pampa
    • Santa Rosa, La Pampa, Argentina, 6300
      • Centro de Salud e Investigaciones Médicas
  • Santa Fe
    • Rosario, Santa Fe, Argentina, 2000
      • Instituto Medico Catamarca Imec
    • Rosario, Santa Fe, Argentina, 2000
      • Instituto de Investigaciones Clínicas Rosario-Sanatorio Delta
  • Tucumán
    • San Miguel De Tucumán, Tucumán, Argentina, T4000AXL
      • Centro de Investigaciones Médicas Tucumán
• Germany
  • Bad Mergentheim, Germany, 97980
    • Diabetespraxis Mergentheim
  • Hamburg, Germany, 22607
    • Diabeteszentrum Hamburg West
  • Hessen
    • Frankfurt, Hessen, Germany, 60596
      • ClinPhenomics GmbH & Co KG
  • Nordrhein-Westfalen
    • Essen, Nordrhein-Westfalen, Germany, 45136
      • InnoDiab Forschung GmbH
    • Münster, Nordrhein-Westfalen, Germany, 48145
      • Institut für Diabetesforschung GmbH Münster
    • Münster, Nordrhein-Westfalen, Germany, 48153
      • Schwerpunktpraxis für Diabetes und Ernährungsmedizin Dr. med. Winfried Keuthage
  • Schleswig-Holstein
    • Oldenburg, Schleswig-Holstein, Germany, 23758
      • RED-Institut GmbH
• India
  • Chandigarh, India, 160012
    • Post Graduate Institute of Medical Education & Research (PGIMER)
  • Karnataka
    • Bangalore, Karnataka, India, 560092
      • Life Care Hospital and Research Centre
  • Maharashtra
    • Mumbai, Maharashtra, India, 400008
      • Topiwala National Medical College & B. Y. L. Nair Charitable Hospital
    • Mumbai, Maharashtra, India, 400058
      • BSES MG hospital
  • Tamil Nadu
    • Chennai, Tamil Nadu, India, 600086
      • Madras Diabetes Research Foundation
  • Telangana
    • Hyderabad, Telangana, India, 500012
      • Osmania General Hospital
• Italy
  • Ancona, Italy, 60125
    • INRCA Ancona
  • Bologna, Italy, 40138
    • IRCCS - AOU di Bologna
  • Brescia, Italy, 25123
    • Azienda Ospedaliera Spedali Civili di Brescia
  • Catanzaro, Italy, 88100
    • Azienda Ospedaliera Mater Domini
  • Palermo, Italy, 90127
    • Azienda di Rilievo Nazionale e Alta Specializzazione Civico Di Cristina Benfratelli
  • Frosinone
    • Ceccano, Frosinone, Italy, 03023
      • Osepdale Civile Fr 5
  • Lazio
    • Roma, Lazio, Italy, 00186
      • "Fatebenefratelli Isola Tiberina - Gemelli Isola"
  • Sardegna
    • Olbia, Sardegna, Italy, 07026
      • Ospedale san Giovanni di Dio-Diabetologia
• Mexico
  • Chihuahua, Mexico, 31217
    • Investigacion En Salud Y Metabolismo Sc
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44670
      • Unidad de Investigación Clínica y Atención Médica HEPA
    • Guadalajara, Jalisco, Mexico, 44670
      • Private Practice - Dr. Arechavaleta Granell Maria del Rosario
  • Nuevo León
    • Monterrey, Nuevo León, Mexico, 66460
      • Hospital Universitario "Dr. Jose Eleuterio Gonzalez"
    • San Nicolás de los Garza, Nuevo León, Mexico, 66465
      • Unidad Médica para la Salud Integral
  • Tamaulipas
    • Ciudad Madero, Tamaulipas, Mexico, 89440
      • Centro de Estudios de Investigacion Metabolicos y Cardiovasculares, S.C.
• Puerto Rico
  • Bayamon, Puerto Rico, 00959
    • Centro de Endocrinologia Alcantara Gonzalez
  • Manati, Puerto Rico, 00674
    • Manati Center for Clinical Research
• Spain
  • Granada, Spain, 18016
    • Hospital Universitario San Cecilio
  • Sevilla, Spain, 41003
    • Clínica nuevas Tecnologías en Diabetes y Endocrinología (NTDE)
  • A Coruña [La Coruña]
    • A Coruña, A Coruña [La Coruña], Spain, 15006
      • CHUAC-Complejo Hospitalario Universitario A Coruña
    • Ferrol, A Coruña [La Coruña], Spain, 15405
      • Complejo Hospitalario Universitario de Ferrol (CHUF)- Hospital Naval
  • Andalucía
    • Malaga, Andalucía, Spain, 29010
      • Hospital Universitario Virgen de la Victoria
  • Balears [Baleares]
    • Palma, Balears [Baleares], Spain, 07120
      • Hospital Universitari Son Espases
  • Castilla Y León
    • Valladolid, Castilla Y León, Spain, 47010
      • Hospital Clinico Universitario de Valladolid
  • Catalunya [Cataluña]
    • Barcelona, Catalunya [Cataluña], Spain, 08041
      • Hospital De La Santa Creu I Sant Pau
  • Madrid
    • Pozuelo de Alarcón, Madrid, Spain, 28223
      • Hospital Universitario Quironsalud Madrid
  • Sevilla
    • Seville, Sevilla, Spain, 41950
      • Vithas Hospital Sevilla
  • Valenciana, Comunitat
    • Alzira, Valenciana, Comunitat, Spain, 46600
      • Hospital Universitario de La Ribera
    • Valencia, Valenciana, Comunitat, Spain, 46014
      • Hospital General Universitario de Valencia
• United States
  • Connecticut
    • Hamden, Connecticut, United States, 06517
      • CMR of Greater New Haven, LLC
  • Florida
    • Clearwater, Florida, United States, 33761
      • Tampa Bay Medical Research
    • Miami Lakes, Florida, United States, 33014
      • Panax Clinical Research
    • Weston, Florida, United States, 33331
      • Encore Medical Research - Weston
  • Idaho
    • Blackfoot, Idaho, United States, 83221
      • Elite Clinical Trials
    • Idaho Falls, Idaho, United States, 83404
      • Rocky Mountain Clinical Research
  • Maryland
    • Baltimore, Maryland, United States, 21239
      • MedStar Good Samaritan Hospital
  • Massachusetts
    • Fall River, Massachusetts, United States, 02721
      • NECCR PrimaCare Research
  • Michigan
    • Troy, Michigan, United States, 48098
      • Arcturus Healthcare , PLC, Troy Internal Medicine Research Division
  • Nevada
    • Las Vegas, Nevada, United States, 89148
      • Palm Research Center Sunset
    • Las Vegas, Nevada, United States, 89128
      • Palm Research Center Tenaya
  • New York
    • Buffalo, New York, United States, 14221
      • Research Foundation of SUNY - University of Buffalo
  • Ohio
    • Columbus, Ohio, United States, 43215
      • Remington Davis Clinical Research
    • Dublin, Ohio, United States, 43016
      • Aventiv Research
  • Pennsylvania
    • Beaver, Pennsylvania, United States, 15009
      • Heritage Valley Multispecialty Group, Inc
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University Hospital
  • Texas
    • Austin, Texas, United States, 78749
      • Texas Diabetes & Endocrinology, P.A.
    • Austin, Texas, United States, 78731
      • Texas Diabetes & Endocrinology, P.A.
    • Dallas, Texas, United States, 75231
      • North Texas Endocrine Center
    • Houston, Texas, United States, 77043
      • Biopharma Informatic, LLC
    • Plano, Texas, United States, 75093
      • Research Institute of Dallas
    • Shavano Park, Texas, United States, 78231
      • Consano Clinical Research, LLC
  • Utah
    • Saint George, Utah, United States, 84790
      • Chrysalis Clinical Research
  • Washington
    • Renton, Washington, United States, 98057
      • Rainier Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 500 U/mL - Insulin Efsitora; Participants received 500 units per milliliter (U/mL) Insulin Efsitora Alfa (insulin efsitora) administered subcutaneously (SC) once weekly (QW) along with 100 U/mL insulin lispro given SC with meals as needed.	Drug: Insulin Lispro (U100); Administered SC; Other Names: Humalog; Drug: Insulin Efsitora Alfa; Administered SC; Other Names: LY3209590 and Basal Insulin-FC
Active Comparator: 100 U/mL - Insulin Glargine; Participants received 100 U/mL insulin glargine administered SC once daily (QD) along with 100 U/mL insulin lispro given SC with meals as needed.	Drug: Insulin Lispro (U100); Administered SC; Other Names: Humalog; Drug: Insulin Glargine (U100); Administered SC; Other Names: Basaglar

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Hemoglobin A1c (HbA1c) [Noninferiority]	HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time.	Baseline, Week 26

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in HbA1c [Superiority]	HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time.	Baseline, Week 26
Percentage of Participants Achieving HbA1c <7% Without Nocturnal Hypoglycemia	Percentage of participants achieving HbA1c <7% without nocturnal hypoglycemia [<54 milligram/deciliter (mg/dL) 3.0 millimole/Liter (mmol/L)] or severe during treatment phase up to week 26. Nocturnal hypoglycemia is a hypoglycemia event, including severe hypoglycemia, that occurs at night and presumably during sleep between midnight and 6:00 am.	Week 26
Nocturnal Hypoglycemia Event Rate	The event rate of participant-reported clinically significant nocturnal hypoglycemia, (where glucose <54 mg/dL (3.0 mmol/L) or severe and occurs at night and presumably during sleep between midnight and 6:00 AM), measured during treatment phase up to week 26. Group mean is reported here.	Baseline Up To Week 26
Change From Baseline in Fasting Glucose	Change from baseline in fasting glucose measured by self-monitoring blood glucose (SMBG).	Baseline, Week 26
Percentage of Time in Glucose Range	Percentage of 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
Percentage of Time in Hypoglycemia Range	Percentage of Time in hypoglycemia range with glucose <54 mg/dL (3.0 mmol/L), measured by CGM.	Week 22 to Week 26
Percentage of Time in Hyperglycemia Range	Percentage of Time in hyperglycemia range with glucose >180 mg/dL (10.0 mmol/L), measured by CGM.	Week 22 to Week 26
Glucose Variability Between Weeks 22 to 26	Glucose variability measured as coefficient of variation for glucose within day for 24-hour period between Week 22 and 26 was reported.	Week 22 to Week 26
Basal Insulin Dose at Week 26	Average weekly basal Insulin Dose at Week 26 was reported.	Week 26
Bolus Insulin Dose at Week 26	Average daily bolus Insulin Dose at Week 26 was reported.	Week 26
Total Insulin Dose at Week 26	Average total weekly insulin dose at Week 26 was reported.	Week 26
Basal Insulin Dose to Total Insulin Dose Ratio at Week 26	Basal insulin dose to total insulin dose ratio at Week 26 was reported.	Week 26
Hypoglycemia Event Rate	Hypoglycemia event rate was reported. 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 here.	Baseline up to Week 26
Change From Baseline in Body Weight	Change from baseline in body weight was reported.	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 diabetes. The Device Characteristic Subscale is comprised of items 1 to 7 which focus on specific characteristics of injection devices. 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

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Investigators: Study Director: Call 1-877-CTLILLY (1-877-285-4559) Mon- Fri 9 AM -5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Publications and helpful links

Helpful Links

• A Study of LY3209590 as a Weekly Basal Insulin Compared to Insulin Glargine in Adult Participants With Type 2 Diabetes on Multiple Daily Injections (QWINT-4)

Study record dates

Study Major Dates

• Study Start (Actual): August 11, 2022
• Primary Completion (Actual): February 27, 2024
• Study Completion (Actual): February 27, 2024

Study Registration Dates

• First Submitted: July 14, 2022
• First Submitted That Met QC Criteria: July 14, 2022
• First Posted (Actual): July 18, 2022

Study Record Updates

• Last Update Posted (Actual): April 27, 2025
• Last Update Submitted That Met QC Criteria: April 10, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Diabetes Mellitus, Type 2; Diabetes Mellitus; Physiological Effects of Drugs; Hypoglycemic Agents; Insulin Glargine; Insulin; Insulin, Globin Zinc; Insulin Lispro
• Other Study ID Numbers: 18260; I8H-MC-BDCV (Other Identifier: Eli Lilly and Company); 2021-005878-25 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No