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Insulin Glargine

Phase 3

Diabetes Mellitus, Type 1 | Small molecule | Metabolic |Eli Lilly and Company|Last Updated: Nov 16, 2022

Target and mechanism

ModalitySmall molecule

Also known as LY2963016, Insulin Glargine (U100)

Success Probability

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Market & Valuation

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Trial Design

RandomizedDouble-BlindACTIVE_CONTROLLEDDMC
Total Trials3
Total Enrollment626

FDA Designations

No designations recorded

Clinical trial landscape

Insulin Glargine · 17 trials · 8 indications

Phase 3 8Phase 2 1Phase 1 8
NCT03338023A Study of LY2963016 Compared to Lantus® in Adult Chinese Participants With Type 1 Diabetes MellitusType 1 Diabetes
COMPLETED272 Analytics
NCT03338010A Study of LY2963016 Compared to Lantus® in Adult Chinese Participants With Type 2 Diabetes MellitusType 2 Diabetes
COMPLETED536 Analytics
NCT02302716A Study of LY2963016 Compared to LANTUS® in Adult Participants With Type 2 Diabetes MellitusDiabetes Mellitus, Type 2
COMPLETED493 Analytics
NCT01421459A Study in Adults With Type 2 DiabetesDiabetes Mellitus, Type 2
COMPLETED759 Analytics
NCT01421147A Study in Adults With Type 1 DiabetesDiabetes Mellitus, Type 1
COMPLETED536 Analytics
NCT01191268A Study in Participants With Type 2 Diabetes Mellitus (AWARD-4)Diabetes Mellitus, Type 2
COMPLETED884 Analytics
NCT01075282A Study in Participants With Type 2 Diabetes Mellitus (AWARD-2)Diabetes Mellitus, Type 2
COMPLETED810 Analytics
NCT00666718A Comparison Study of Basal Bolus Therapies Together With Lispro Insulin in Type 2 Diabetes PatientsDiabetes Mellitus, Type 2
COMPLETED374 Analytics
PHASE3COMPLETED
A Study of LY2963016 Compared to Lantus® in Adult Chinese Participants With Type 1 Diabetes Mellitus
Type 1 DiabetesUnlock trial analytics
PHASE3COMPLETED
A Study of LY2963016 Compared to Lantus® in Adult Chinese Participants With Type 2 Diabetes Mellitus
Type 2 DiabetesUnlock trial analytics
PHASE3COMPLETED
A Study of LY2963016 Compared to LANTUS® in Adult Participants With Type 2 Diabetes Mellitus
Diabetes Mellitus, Type 2Unlock trial analytics
PHASE3COMPLETED
A Study in Adults With Type 2 Diabetes
Diabetes Mellitus, Type 2Unlock trial analytics
PHASE3COMPLETED
A Study in Adults With Type 1 Diabetes
Diabetes Mellitus, Type 1Unlock trial analytics
PHASE3COMPLETED
A Study in Participants With Type 2 Diabetes Mellitus (AWARD-4)
Diabetes Mellitus, Type 2Unlock trial analytics
PHASE3COMPLETED
A Study in Participants With Type 2 Diabetes Mellitus (AWARD-2)
Diabetes Mellitus, Type 2Unlock trial analytics
PHASE3COMPLETED
A Comparison Study of Basal Bolus Therapies Together With Lispro Insulin in Type 2 Diabetes Patients
Diabetes Mellitus, Type 2Unlock trial analytics

Study Endpoints

Primary Endpoints

Change From Baseline in Hemoglobin A1c (HbA1c) (LY2963016 Noninferior to Lantus®)
Baseline, Week 24

HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. Least square (LS) mean was calculated using mixed-effects model for repeated measures (MMRM) with variables baseline HbA1c + Treatment + Pre-study treatment + Pre-study metformin or acarbose usage + Time + Time\*Treatment (Type III sum of squares).

Change From Baseline in Hemoglobin A1c (HbA1c) (LY2963016 to Lantus®)
Baseline, Week 24

HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. Least square (LS) mean was calculated by mixed-effects model for repeated measures (MMRM) with baseline, insulin secretagogues at study entry, treatment, visit and treatment\*visit in the model.

Change From Baseline to 24 Weeks in Hemoglobin A1c (HbA1c)
Baseline, 24 weeks

HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with baseline of response, treatment (LY2963016, LANTUS), pooled country, basal insulin at entry (yes/no), sulfonylurea (SU) use (yes/no), visit, treatment and visit\*treatment in the model.

Change From Baseline up to 24 Weeks in Hemoglobin A1c (HbA1c)
Baseline, Endpoint (up to 24 weeks)

HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. Least Squares (LS) mean was determined by analysis of covariance (ANCOVA) and adjusted for Baseline HbA1c, country, sulfonylurea use, time of basal insulin injection and treatment.

Change From Baseline to 26-week Endpoint in Glycosylated Hemoglobin (HbA1c)
Baseline, 26 weeks

Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) adjusted by treatment, country, baseline metformin, and baseline HbA1c.

Change From Baseline to 52 Weeks Endpoint in Glycosylated Hemoglobin (HbA1c)
Baseline, 52 weeks

Least Squares (LS) means were calculated using analysis of covariance (ANCOVA) with country and treatment as fixed effects and baseline HbA1c as a covariate.

Change From Baseline in Hemoglobin A1c (HbA1c) to Week 24
Baseline, Week 24

Least Squares Mean (LSMean) values reported in the table were controlled for treatment, country, and baseline HbA1c value.

Change in HbA1c from baseline
12 and 24 weeks
Incidence of Documented Hypoglycemia
Baseline through Day 186
Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of Insulin Glargine and Lantus
-0.5 and 0 hours predose; 0.5, 1, 2, 3, 4, 6, 9, 12, 15, 18, 21, and 24 hours postdose

Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of Insulin glargine and Lantus.

PK: Area Under the Concentration Versus Time Curve From Time Zero to 24 Hours (AUC[0-24]) of Insulin Glargine and Lantus
-0.5 and 0 hours predose; 0.5, 1, 2, 3, 4, 6, 9, 12, 15, 18, 21, and 24 hours postdose

PK: Area Under the Concentration Versus Time Curve From Time Zero to 24 Hours (AUC\[0-24\]) of Insulin glargine and Lantus.

Pharmacokinetics: Maximum Observed Drug Concentration (Cmax) of LY2963016 U-200 Formulation and LY2963016 U-100 Formulation
One hour before dosing up to 48 hours following administration of study drug
Pharmacokinetics: Area Under the Concentration Versus Time Curve (AUC) of LY2963016 U-200 Formulation and LY2963016 U-100 Formulation
One hour before dosing up to 48 hours following administration of study drug
Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of LY2963016 and US-Approved Lantus
30 minutes predose up to 24 hours postdose in all treatment periods

The AUC from time 0 to 24 hours (AUC0-24) of LY2963016 and US-Approved Lantus was measured.

Pharmacokinetics (PK): Maximum Plasma Concentration (Cmax) of LY2963016 and US-Approved Lantus
30 minutes predose up to 24 hours postdose in all treatment periods
Pharmacokinetics: Area Under the Serum LY2963016 or Lantus Concentration-Time Curve (AUC) From Zero to Infinity [AUC(0-∞)]
Predose up to 24 hours after administration of study drug

Results for LY2936016 treatment arms provide the AUC(0-∞) data for LY2936016, while the results for Lantus treatment arms provide the AUC(0-∞) for Lantus.

Pharmacokinetics: Maximum Serum LY2963016 or Lantus Concentration (Cmax)
Predose up to 24 hours after administration of study drug
Pharmacodynamics: Duration of Action of LY2963016 and Lantus
Periods 1 and 2: Baseline up to 42 hours postdose

Duration of action is defined as the period of time elapsed between dose administration and the time at which the participant's blood glucose is consistently \>150 milligrams/deciliter (mg/dL) without any glucose infusion. Participants whose blood glucose did not rise to 150 mg/dL were censored 42 hours postdose.

Pharmacokinetics: Area Under the Concentration-Time Curve From Time Zero to 24 Hours [AUC(0-24)] of LY2963016 and Lantus
1 hour predose up to 24 hours postdose in all treatment periods
Pharmacokinetics: Maximum Plasma Concentration (Cmax) of LY2963016 and Lantus
1 hour predose up to 24 hours postdose in all treatment periods
Pharmacokinetics: Area Under the Concentration-Time Curve (AUC)
Periods 1 and 2: Baseline up to 24 hours

AUC from time zero to 24 hours (AUC0-24) is reported for this outcome measure.

Secondary Endpoints

Change From Baseline in HbA1c (Lantus® Noninferior to LY2963016)
Baseline, Week 24
Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) Values
Baseline, Week 24
Percentage of Participants With HbA1c <7%
Week 24
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Study Design & Arms

AllocationRANDOMIZED
MaskingNONE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
LY2963016 + Insulin LisproEXPERIMENTALParticipants received 100 units per milliliter (U/mL) LY2963016 administered subcutaneously (SC) once daily (QD) and 100 U/mL premeal insulin lispro administered SC thrice-daily (TID) within 15 minutes before meals or immediately after the meal.
Lantus® + Insulin LisproACTIVE_COMPARATORParticipants received 100 U/mL Lantus® administered SC QD and 100 U/mL premeal insulin lispro administered SC thrice-daily (TID) within 15 minutes before meals or immediately after the meal.
LY2963016EXPERIMENTALInsulin naive participants started on 10 units (U) LY2963016 given subcutaneously (SC) once a day (QD) for 24 weeks. Participants-driven titration was supervised by investigators through the course of the study to maintain the fasting blood glucose (FBG) ≤100 milligram per deciliter (mg/dL) (5.6 millimoles per litre \[mmol/L\]) while avoiding hypoglycemia. Participants were allowed to continue oral antihyperglycemic medication (OAM).
Lantus®ACTIVE_COMPARATORInsulin naive participants started on 10 U Lantus® given SC QD for 24 weeks. Participants-driven titration was supervised by investigators through the course of the study to maintain the FBG ≤100 mg/dL (5.6 mmol/L) while avoiding hypoglycemia. Participants were allowed to continue oral OAM.
LY2963016 + OAMsEXPERIMENTALLY2963016 titrated based on blood glucose readings, administered subcutaneously, once daily in combination with at least 2 oral antihyperglycemic medications (OAMs) \[alpha glucosidase inhibitors (AGI), dipeptidyl peptidases intravenous (DPP-IV), meglitinide (MEG), metformin (MET), sulfonylurea (SU), and thiazolidinedione (TZD)\] administered per standard of care for 24 weeks
Lantus + OAMsACTIVE_COMPARATORLantus titrated based on blood glucose readings, administered subcutaneously, once daily in combination with at least 2 OAMs (AGI, DPP-IV, MEG, MET, SU, and TZD) administered per standard of care for 24 weeks
Lantus + Insulin LisproACTIVE_COMPARATORLantus titrated based on blood glucose readings, administered subcutaneously, once daily at the same timing (daytime or evening/bedtime) as participant's prestudy basal insulin injection schedule in combination with premeal insulin lispro. Insulin lispro titrated based on blood glucose readings, administered subcutaneously, three times a day for 52 weeks.
1.5 mg LY2189265EXPERIMENTALLY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks
0.75 mg LY2189265EXPERIMENTALLY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks
Insulin GlargineACTIVE_COMPARATORInsulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks
LY2189265 1.5 mgEXPERIMENTALLY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks
LY2189265 0.75 mgEXPERIMENTALLY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks
GlargineACTIVE_COMPARATORGlargine plus Insulin Lispro (2-3 injections)
ILPSEXPERIMENTALInsulin Lispro Protamine Suspension (ILPS) plus Insulin Lispro (2-3 injections)
1EXPERIMENTAL -
2EXPERIMENTAL -
Insulin Glargine (Period 1)ACTIVE_COMPARATORInsulin glargine administered subcutaneously (SC).
LY3209590 (Period 2)EXPERIMENTALLY3209590 administered SC.
LantusACTIVE_COMPARATORParticipants received 0.5 U/Kg of Lantus subcutaneously.
LY2963016 U-200 Formulation (Test)EXPERIMENTALLY2963016 test formulation administered as a subcutaneous (SC) injection in one of two or two of four study periods.
LY2963016 U-100 Formulation (Reference)EXPERIMENTALLY2963016 reference formulation administered as a SC injection in one of two or two of four study periods.
US-approved LantusEXPERIMENTALSingle 0.5 U/kg dose of US-approved Lantus administered subcutaneously, twice during the study
0.3 U/kg LY2963016EXPERIMENTALSingle 0.3 units/kilogram (U/kg) subcutaneous dose of LY2963016
0.3 U/kg LantusEXPERIMENTALSingle 0.3 U/kg subcutaneous dose of Lantus
0.6 U/kg LY2963016EXPERIMENTALSingle 0.6 U/kg subcutaneous dose of LY2963016
0.6 U/kg LantusEXPERIMENTALSingle 0.6 U/kg subcutaneous dose of Lantus

Interventions

NameTypeDescription
LY2963016DRUGAdministered SC
Lantus®DRUGAdministered SC
Insulin LisproDRUGAdministered SC
Oral Antihyperglycemic MedicationDRUGAdministered as per standard-of-care.
LantusDRUGAdministered subcutaneously
OAMsDRUGAdministered orally
Insulin GlargineDRUG -
LY2189265DRUG -
MetforminDRUG -
GlimepirideDRUG -
Insulin Lispro Protamine Suspension (ILPS)DRUGpatient glucose-level dependent, injection, once daily in the evening, 24 weeks
Human Insulin Inhalation PowderDRUGpatient specific dose, inhaled, before meals,12 weeks
Injectable InsulinDRUGPatient specific dose,injected, before meals, 12 weeks
LY3209590DRUGAdministered SC
US Approved LantusDRUGAdministered subcutaneously
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Eligibility Criteria

Age Range18 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites20

Inclusion Criteria: * Have T1DM based on the disease diagnostic criteria (World Health Organization \[WHO\] Classification). * Have duration of T1DM ≥1 year. * Have HbA1c ≤11 %. * Have been administered with basal-bolus insulins or pre-mixed insulins for at least 90 days prior to screening. * Have ...

Countries:ChinaUnited StatesIndiaPuerto RicoRussiaSouth KoreaTaiwanTurkey (Türkiye)CzechiaFranceGermanyGreeceHungaryMexicoPolandSpainBelgiumJapanRomaniaArgentinaAustraliaBrazilCanadaDenmarkSwedenCroatiaItalySlovakiaUnited KingdomSingaporeSouth Africa
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Frequently asked questions about Insulin Glargine

What is LY2963016 used for?

LY2963016 is an investigational basal insulin studied for use in diabetes mellitus, including Type 1 and Type 2 diabetes. It has been evaluated in healthy participants and in adult Chinese participants with Type 1 diabetes. The drug is being developed by Eli Lilly and Company as a potential treatment option for these metabolic conditions.

What does LY2963016 target?

LY2963016 is a basal insulin, meaning it targets the insulin receptor to provide a long-acting, steady level of insulin activity. It is designed to mimic the body's basal insulin secretion to help control blood glucose levels in people with diabetes. The drug is compared against Lantus (insulin glargine) in clinical trials.

Who makes LY2963016?

LY2963016 is being developed by Eli Lilly and Company, a pharmaceutical company traded on the New York Stock Exchange under the ticker symbol LLY. Eli Lilly is conducting clinical trials to evaluate the safety and efficacy of this basal insulin for the treatment of diabetes mellitus.

What phase is LY2963016 in?

LY2963016 has completed Phase 1 and Phase 3 clinical trials. The Phase 1 studies evaluated the drug in healthy participants, while a Phase 3 study was conducted in adult Chinese participants with Type 1 diabetes. All trials listed for LY2963016 are completed, with no active trials currently ongoing.

What clinical trials is LY2963016 in?

LY2963016 has been studied in several completed clinical trials. These include NCT01374178 and NCT01688635, which compared LY2963016 to basal insulin or Lantus in healthy subjects, NCT02955953 comparing two formulations of insulin glargine, and NCT03338023, a Phase 3 study in Chinese participants with Type 1 diabetes.

Is LY2963016 the same as Lantus?

LY2963016 is not the same as Lantus, but it is being studied as a potential biosimilar or comparable product to Lantus (insulin glargine). Clinical trials have directly compared LY2963016 to Lantus to assess similarity in pharmacokinetics and efficacy. The drug is an investigational basal insulin developed by Eli Lilly.