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

Phase 3

Completed

Conditions: Type 2 Diabetes Treated With Insulin
Type 2 Diabetes

Interventions: Drug: Insulin Efsitora Alfa
Drug: Insulin Lispro (U100)
Drug: Insulin Glargine (U100)

Registration Number: NCT05462756

Lead Sponsor: Eli Lilly and Company

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 730

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 & 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) along with 100 U/mL insulin lispro given SC with meals as needed.
500 U/mL - Insulin Efsitora	Insulin Lispro (U100)	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.
100 U/mL - Insulin Glargine	Insulin Lispro (U100)	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.
100 U/mL - Insulin Glargine	Insulin Glargine (U100)	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.
Insulin Efsitora Alfa + Insulin Lispro	Insulin Efsitora Alfa	Participants will be given insulin efsitora alfa by subcutaneous (SC) injection along with insulin lispro
Insulin Glargine + Insulin Lispro	Insulin Lispro (U100)	Participants will be given insulin glargine by SC injection along with insulin lispro
Insulin Glargine + Insulin Lispro	Insulin Glargine (U100)	Participants will be given insulin glargine by SC injection along with insulin lispro
Insulin Efsitora Alfa + Insulin Lispro	Insulin Lispro (U100)	Participants will be given insulin efsitora alfa by subcutaneous (SC) injection along with insulin lispro

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.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in 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.
Percentage of Participants Achieving HbA1c <7% Without Nocturnal Hypoglycemia	Week 26	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.
Nocturnal Hypoglycemia Event Rate	Baseline Up To Week 26	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.
Change From Baseline in Fasting Glucose	Baseline, Week 26	Change from baseline in fasting glucose measured by self-monitoring blood glucose (SMBG).
Percentage of Time in Glucose Range	Week 22 to Week 26	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.
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 by CGM.
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 by CGM.
Glucose Variability Between Weeks 22 to 26	Week 22 to Week 26	Glucose variability measured as coefficient of variation for glucose within day for 24-hour period between Week 22 and 26 was reported.
Basal Insulin Dose at Week 26	Week 26	Average weekly basal Insulin Dose at Week 26 was reported.
Bolus Insulin Dose at Week 26	Week 26	Average daily bolus Insulin Dose at Week 26 was reported.
Total Insulin Dose at Week 26	Week 26	Average total weekly insulin dose at Week 26 was reported.
Basal Insulin Dose to Total Insulin Dose Ratio at Week 26	Week 26	Basal insulin dose to total insulin dose ratio at Week 26 was reported.
Hypoglycemia Event Rate	Baseline up to Week 26	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.
Change From Baseline in Body Weight	Baseline, Week 26	Change from baseline in body weight was reported.
Treatment Experience for Diabetes Injection Device at Week 26 - Experience Questionnaire (DID-EQ)	Week 26	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

Trial Locations

Locations (80): Palm Research Center Tenaya
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Las Vegas, Nevada, United States
Palm Research Center Sunset
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Las Vegas, Nevada, United States
Biopharma Informatic, LLC
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Houston, Texas, United States
Panax Clinical Research
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Miami Lakes, Florida, United States
Tampa Bay Medical Research
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Clearwater, Florida, United States
Encore Medical Research - Weston
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Weston, Florida, United States
Rocky Mountain Clinical Research
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Idaho Falls, Idaho, United States
MedStar Good Samaritan Hospital
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Baltimore, Maryland, United States
Remington Davis Clinical Research
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Columbus, Ohio, United States
Research Foundation of SUNY - University of Buffalo
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Buffalo, New York, United States
Aventiv Research
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Dublin, Ohio, United States
Texas Diabetes & Endocrinology, P.A.
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Austin, Texas, United States
Heritage Valley Multispecialty Group, Inc
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Beaver, Pennsylvania, United States
Thomas Jefferson University Hospital
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Philadelphia, Pennsylvania, United States
North Texas Endocrine Center
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Dallas, Texas, United States
Research Institute of Dallas
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Plano, Texas, United States
Consano Clinical Research, LLC
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Shavano Park, Texas, United States
Chrysalis Clinical Research
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Saint George, Utah, United States
Rainier Clinical Research Center
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Renton, Washington, United States
CEDIC
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Caba, Buenos Aires, Argentina
Centro de Investigaciones Metabólicas (CINME)
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Ciudad Autónoma de Buenos Aire, Buenos Aires, Argentina
Centro Medico Dra. Laura Maffei- Investigacion Clinica Aplicada
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Ciudad Autonoma de Buenos Aire, Ciudad Autónoma De Buenos Aire, Argentina
Instituto Médico Río Cuarto
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Río Cuarto, Córdoba, Argentina
Instituto de Investigaciones Clinicas Rosario-Sanatorio Delta
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Rosario, Santa Fe, Argentina
Instituto de Investigaciones Clínicas Córdoba
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Córdoba, Argentina
ClinPhenomics GmbH & Co KG
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Frankfurt, Hessen, Germany
Institut für Diabetesforschung GmbH Münster
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Münster, Nordrhein-Westfalen, Germany
InnoDiab Forschung Gmbh
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Essen, Nordrhein-Westfalen, Germany
Schwerpunktpraxis für Diabetes und Ernährungsmedizin Dr. med. Winfried Keuthage
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Münster, Nordrhein-Westfalen, Germany
Diabetespraxis Mergentheim
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Bad Mergentheim, Germany
Diabeteszentrum Hamburg West
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Hamburg, Germany
Osepdale Civile Fr 5
🇮🇹
Ceccano, Frosinone, Italy
Post Graduate Institute of Medical Education & Research (PGIMER)
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Chandigarh, India
Ospedale san Giovanni di Dio-Diabetologia
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Olbia, Sardegna, Italy
INRCA Ancona
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Ancona, Italy
Private Practice - Dr. Arechavaleta Granell Maria del Rosario
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Guadalajara, Jalisco, Mexico
Unidad de Investigación Clínica y Atención Médica HEPA
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Guadalajara, Jalisco, Mexico
Centro de Endocrinologia Alcantara Gonzalez
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Bayamon, Puerto Rico
CHUAC-Complejo Hospitalario Universitario A Coruña
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A Coruña, A Coruña [La Coruña], Spain
Complejo Hospitalario Universitario de Ferrol (CHUF)- Hospital Naval
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Ferrol, A Coruña [La Coruña], Spain
Hospital Universitario Virgen de la Victoria
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Malaga, Andalucía, Spain
Hospital Clínico Universitario de Valladolid
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Valladolid, Castilla Y León, Spain
Hospital Universitari Son Espases
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Palma, Balears [Baleares], Spain
Hospital Universitario Quironsalud Madrid
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Pozuelo de Alarcón, Madrid, Spain
Hospital de la Santa Creu i Sant Pau
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Barcelona, Catalunya [Cataluña], Spain
Hospital Universitario de La Ribera
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Alzira, Valenciana, Comunitat, Spain
Hospital General Universitario de Valencia
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Valencia, Valenciana, Comunitat, Spain
Hospital Universitario San Cecilio
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Granada, Spain
Clínica nuevas Tecnologías en Diabetes y Endocrinología (NTDE)
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Sevilla, Spain
Madras Diabetes Research Foundation
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Chennai, Tamil Nadu, India
RED-Institut GmbH
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Oldenburg, Schleswig-Holstein, Germany
Arcturus Healthcare , PLC, Troy Internal Medicine Research Division
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Troy, Michigan, United States
CENUDIAB
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Ciudad Autónoma de Buenos Aires, Argentina
"Fatebenefratelli Isola Tiberina - Gemelli Isola"
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Roma, Lazio, Italy
Hospital Universitario "Dr. Jose Eleuterio Gonzalez"
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Monterrey, Nuevo León, Mexico
Consultorio de Investigación Clínica EMO SRL
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Ciudad Autonoma de Buenos Aire, Buenos Air, Argentina
Life Care Hospital and Research Centre
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Bangalore, Karnataka, India
NECCR PrimaCare Research
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Fall River, Massachusetts, United States
CMR of Greater New Haven, LLC
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Hamden, Connecticut, United States
Go Centro Medico San Nicolás
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San Nicolas, Buenos Aires, Argentina
CIPREC
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Caba, Ciudad Autónoma De Buenos Aires, Argentina
Elite Clinical Trials
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Blackfoot, Idaho, United States
Centro de Investigaciones Médicas Tucuman
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San Miguel De Tucumán, Tucumán, Argentina
Instituto Médico Catamarca IMEC
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Rosario, Santa Fe, Argentina
Instituto Centenario
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Caba, Ciudad Autónoma De Buenos Aire, Argentina
Unidad Médica para la Salud Integral
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San Nicolás de los Garza, Nuevo León, Mexico
Centro de Investigaciones Clinicas del Litoral
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Santa Fe, Argentina
Osmania General Hospital
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Hyderabad, Telangana, India
Mautalen Salud e Investigación
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Buenos Aires, Ciudad Autónoma De Buenos Aires, Argentina
Vithas Hospital Sevilla
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Seville, Sevilla, Spain
Topiwala National Medical College & B. Y. L. Nair Charitable Hospital
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Mumbai, Maharashtra, India
BSES MG Hospital
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Mumbai, Maharashtra, India
Investigacion En Salud Y Metabolismo Sc
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Chihuahua, Mexico
Manati Center for Clinical Research
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Manati, Puerto Rico
Centro de Estudios de Investigacion Metabolicos y Cardiovasculares, S.C.
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Ciudad Madero, Tamaulipas, Mexico
IRCCS - AOU di Bologna
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Bologna, Italy
Azienda Ospedaliera Spedali Civili di Brescia
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Brescia, Italy
Azienda Ospedaliera Mater Domini
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Catanzaro, Italy
Azienda di Rilievo Nazionale e Alta Specializzazione Civico Di Cristina Benfratelli
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Palermo, Italy
Centro de Salud e Investigaciones Médicas
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Santa Rosa, La Pampa, Argentina