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

NCT05462756 | Completed Phase 3 Results DMC FDA Drug

• 3 other identifiers: 18260I8H-MC-BDCV2021-005878-25
• Study Type: interventional
• Target: 730
• Locations: 8 countries
• Sites: 81

Brief Summary

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.

Conditions

Type 2 Diabetes; Type 2 Diabetes Treated With Insulin

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (15)

• Change From Baseline in HbA1c [Superiority]

  Baseline, Week 26

• Percentage of Participants Achieving HbA1c <7% Without Nocturnal Hypoglycemia

  Week 26

• Nocturnal Hypoglycemia Event Rate

  Baseline Up To Week 26

• Change From Baseline in Fasting Glucose

  Baseline, Week 26

• Percentage of Time in Glucose Range

  Week 22 to Week 26

Study Arms (2)

500 U/mL - Insulin Efsitora

EXPERIMENTAL

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 Efsitora Alfa; Drug: Insulin Lispro (U100)

100 U/mL - Insulin Glargine

ACTIVE COMPARATOR

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); Drug: Insulin Glargine (U100)

Interventions

Insulin Efsitora Alfa DRUG

Administered SC

Also known as: LY3209590 and Basal Insulin-FC

500 U/mL - Insulin Efsitora

Insulin Lispro (U100) DRUG

Administered SC

Also known as: Humalog

100 U/mL - Insulin Glargine; 500 U/mL - Insulin Efsitora

Insulin Glargine (U100) DRUG

Administered SC

Also known as: Basaglar

100 U/mL - Insulin Glargine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (81)

CMR of Greater New Haven, LLC

Hamden, Connecticut, 06517, United States

Location

Tampa Bay Medical Research

Clearwater, Florida, 33761, United States

Location

Panax Clinical Research

Miami Lakes, Florida, 33014, United States

Location

Encore Medical Research - Weston

Weston, Florida, 33331, United States

Location

Elite Clinical Trials

Blackfoot, Idaho, 83221, United States

Location

Rocky Mountain Clinical Research

Idaho Falls, Idaho, 83404, United States

Location

MedStar Good Samaritan Hospital

Baltimore, Maryland, 21239, United States

Location

NECCR PrimaCare Research

Fall River, Massachusetts, 02721, United States

Location

Arcturus Healthcare , PLC, Troy Internal Medicine Research Division

Troy, Michigan, 48098, United States

Location

Palm Research Center Tenaya

Las Vegas, Nevada, 89128, United States

Location

Palm Research Center Sunset

Las Vegas, Nevada, 89148, United States

Location

Research Foundation of SUNY - University of Buffalo

Buffalo, New York, 14221, United States

Location

Remington Davis Clinical Research

Columbus, Ohio, 43215, United States

Location

Aventiv Research

Dublin, Ohio, 43016, United States

Location

Heritage Valley Multispecialty Group, Inc

Beaver, Pennsylvania, 15009, United States

Location

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

Texas Diabetes & Endocrinology, P.A.

Austin, Texas, 78731, United States

Location

Texas Diabetes & Endocrinology, P.A.

Austin, Texas, 78749, United States

Location

North Texas Endocrine Center

Dallas, Texas, 75231, United States

Location

Biopharma Informatic, LLC

Houston, Texas, 77043, United States

Location

Research Institute of Dallas

Plano, Texas, 75093, United States

Location

Consano Clinical Research, LLC

Shavano Park, Texas, 78231, United States

Location

Chrysalis Clinical Research

St. George, Utah, 84790, United States

Location

Rainier Clinical Research Center

Renton, Washington, 98057, United States

Location

CEDIC

CABA, Buenos Aires, C1060ABN, Argentina

Location

Centro de Investigaciones Metabólicas (CINME)

Ciudad Autónoma de Buenos Aire, Buenos Aires, 1056, Argentina

Location

Go Centro Medico San Nicolás

San Nicolás de los Arroyos, Buenos Aires, 2900, Argentina

Location

Mautalen Salud e Investigación

Buenos Aires, Buenos Aires F.D., C1128AAF, Argentina

Location

CIPREC

CABA, Buenos Aires F.D., C1061AAS, Argentina

Location

Consultorio de Investigación Clínica EMO SRL

Ciudad Autonoma de Buenos Aire, Buenos Air, C1405BUB, Argentina

Location

Instituto Centenario

CABA, Ciudad Autónoma de Buenos Aire, 1204, Argentina

Location

Centro Medico Dra. Laura Maffei- Investigacion Clinica Aplicada

Ciudad Autonoma de Buenos Aire, Ciudad Autónoma de Buenos Aire, C1425AGC, Argentina

Location

Instituto Médico Río Cuarto

Río Cuarto, Córdoba Province, 5800, Argentina

Location

Centro de Salud e Investigaciones Médicas

Santa Rosa, La Pampa Province, 6300, Argentina

Location

Instituto de Investigaciones Clinicas Rosario-Sanatorio Delta

Rosario, Santa Fe Province, 2000, Argentina

Location

Instituto Médico Catamarca IMEC

Rosario, Santa Fe Province, 2000, Argentina

Location

Centro de Investigaciones Médicas Tucuman

San Miguel de Tucumán, Tucumán Province, T4000AXL, Argentina

Location

CENUDIAB

Buenos Aires, C1440AAD, Argentina

Location

Instituto de Investigaciones Clínicas Córdoba

Córdoba, 5000, Argentina

Location

Centro de Investigaciones Clinicas del Litoral

Santa Fe, 3000, Argentina

Location

ClinPhenomics GmbH & Co KG

Frankfurt am Main, Hesse, 60596, Germany

Location

InnoDiab Forschung Gmbh

Essen, North Rhine-Westphalia, 45136, Germany

Location

Institut für Diabetesforschung GmbH Münster

Münster, North Rhine-Westphalia, 48145, Germany

Location

Schwerpunktpraxis für Diabetes und Ernährungsmedizin Dr. med. Winfried Keuthage

Münster, North Rhine-Westphalia, 48153, Germany

Location

RED-Institut GmbH

Oldenburg in Holstein, Schleswig-Holstein, 23758, Germany

Location

Diabetespraxis Mergentheim

Bad Mergentheim, 97980, Germany

Location

Diabeteszentrum Hamburg West

Hamburg, 22607, Germany

Location

Life Care Hospital and Research Centre

Bangalore, Karnataka, 560092, India

Location

Topiwala National Medical College & B. Y. L. Nair Charitable Hospital

Mumbai, Maharashtra, 400008, India

Location

BSES MG Hospital

Mumbai, Maharashtra, 400058, India

Location

Madras Diabetes Research Foundation

Chennai, Tamil Nadu, 600086, India

Location

Osmania General Hospital

Hyderabad, Telangana, 500012, India

Location

Post Graduate Institute of Medical Education & Research (PGIMER)

Chandigarh, 160012, India

Location

Osepdale Civile Fr 5

Ceccano, Frosinone, 03023, Italy

Location

"Fatebenefratelli Isola Tiberina - Gemelli Isola"

Rome, Lazio, 00186, Italy

Location

Ospedale san Giovanni di Dio-Diabetologia

Olbia, Sardinia, 07026, Italy

Location

INRCA Ancona

Ancona, 60125, Italy

Location

IRCCS - AOU di Bologna

Bologna, 40138, Italy

Location

Azienda Ospedaliera Spedali Civili di Brescia

Brescia, 25123, Italy

Location

Azienda Ospedaliera Mater Domini

Catanzaro, 88100, Italy

Location

Azienda di Rilievo Nazionale e Alta Specializzazione Civico Di Cristina Benfratelli

Palermo, 90127, Italy

Location

Private Practice - Dr. Arechavaleta Granell Maria del Rosario

Guadalajara, Jalisco, 44670, Mexico

Location

Unidad de Investigación Clínica y Atención Médica HEPA

Guadalajara, Jalisco, 44670, Mexico

Location

Hospital Universitario "Dr. Jose Eleuterio Gonzalez"

Monterrey, Nuevo León, 66460, Mexico

Location

Unidad Médica para la Salud Integral

San Nicolás de los Garza, Nuevo León, 66465, Mexico

Location

Centro de Estudios de Investigacion Metabolicos y Cardiovasculares, S.C.

Ciudad Madero, Tamaulipas, 89440, Mexico

Location

Investigacion En Salud Y Metabolismo Sc

Chihuahua City, 31217, Mexico

Location

Centro de Endocrinologia Alcantara Gonzalez

Bayamón, 00959, Puerto Rico

Location

Manati Center for Clinical Research

Manatí, 00674, Puerto Rico

Location

CHUAC-Complejo Hospitalario Universitario A Coruña

A Coruña, A Coruña [La Coruña], 15006, Spain

Location

Complejo Hospitalario Universitario de Ferrol (CHUF)- Hospital Naval

Ferrol, A Coruña [La Coruña], 15405, Spain

Location

Hospital Universitario Virgen de la Victoria

Málaga, Andalusia, 29010, Spain

Location

Hospital Universitari Son Espases

Palma, Balears [Baleares], 07120, Spain

Location

Hospital Clínico Universitario de Valladolid

Valladolid, Castille and León, 47010, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, Catalunya [Cataluña], 08041, Spain

Location

Hospital Universitario Quironsalud Madrid

Pozuelo de Alarcón, Madrid, 28223, Spain

Location

Vithas Hospital Sevilla

Seville, Sevilla, 41950, Spain

Location

Hospital Universitario de La Ribera

Alzira, Valenciana, Comunitat, 46600, Spain

Location

Hospital General Universitario de Valencia

Valencia, Valenciana, Comunitat, 46014, Spain

Location

Hospital Universitario San Cecilio

Granada, 18016, Spain

Location

Clínica nuevas Tecnologías en Diabetes y Endocrinología (NTDE)

Seville, 41003, Spain

Location

Related Publications (2)

• Miller E, Davidson MB, Bajaj HS, Rosenstock J, Philis-Tsimikis A, Bergenstal RM, Case M, Ilag L, Threlkeld R, Levasseur E, Gelsey F. Evaluation of Overall Health State, Treatment Burden, and Satisfaction with Insulin Efsitora Alfa (Efsitora) vs. Daily Comparator in Adults with Type 2 Diabetes in the QWINT Clinical Trial Program. Diabetes Ther. 2026 Jan 27. doi: 10.1007/s13300-025-01833-5. Online ahead of print.

  PMID: 41591636 DERIVED

• Blevins T, Dahl D, Perez Manghi FC, Murthy S, Ortiz Carrasquillo R, Li X, Chang AM, Carr MC, Katz M. Once-weekly insulin efsitora alfa versus once-daily insulin glargine U100 in adults with type 2 diabetes treated with basal and prandial insulin (QWINT-4): a phase 3, randomised, non-inferiority trial. Lancet. 2025 Jun 28;405(10497):2290-2301. doi: 10.1016/S0140-6736(25)01069-4. Epub 2025 Jun 22.

  PMID: 40562048 DERIVED

Related 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)

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Insulin Lispro; Insulin Glargine

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Insulin, Short-Acting; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Insulin, Long-Acting

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

ClinicalTrials.gov@lilly.com

800-545-5979

Study Officials

• 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

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 14, 2022
• First Posted: July 18, 2022
• Study Start: August 11, 2022
• Primary Completion: February 27, 2024
• Study Completion: February 27, 2024
• Last Updated: April 27, 2025
• Results First Posted: April 27, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.

Locations

IN (6); ME (6); US (24); IT (8); ES (12); AR (16); DE (7); PR (2)