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CompletedNCT04605991Updated Mar 3, 2023Results posted

A Study of Mealtime Insulin LY900014 in Participants With Type 2 Diabetes Using Continuous Glucose Monitoring (PRONTO-Time in Range)

A Phase 3 interventional study of LY900014 and Insulin Glargine in Type 2 Diabetes, sponsored by Eli Lilly and Company. Completed at 32 sites in 2 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-03-03.

Sponsored by Eli Lilly and Company · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
187
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study summary

This study is being done to evaluate glycemic control in participants with type 2 diabetes who are taking mealtime insulin LY900014 in combination with long-acting insulin glargine. Participants will use continuous glucose monitoring (CGM) (Freestyle Libre 14-day system) during the study.

02

Conditions studied

  • Type 2 Diabetes
03

In context

Diabetes Mellitus

10,925 studies on the registry are indexed under Diabetes Mellitus; 1,319 are open to participants now.

This study's enrollment of 187 is above the median of 80 across 8,367 interventional studies indexed under Diabetes Mellitus.

Browse Diabetes Mellitus studies →

Lead sponsor

Eli Lilly and Company is the lead sponsor of 2,048 studies on the registry; 140 are open to participants now.

Of its 521 completed or terminated interventional studies of FDA-regulated products, 341 (65%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Participants diagnosed (clinically) with type 2 diabetes mellitus (T2D) for at least 1 year prior to screening.

  • Have been treated with basal-bolus multiple daily injection (MDI) therapy for at least 90 days prior to screening including:

    • Basal insulin glargine U-100, in combination with bolus insulin analog (insulin lispro, insulin aspart, or insulin glulisine) with meals.
    • Participant must have been treated with the same type of allowed bolus insulin analog for at least 30 days prior to screening.

  • Participants may be treated with up to 3 of the following oral antihyperglycemic medications (OAMs) for T2D in accordance with local regulations:

    1. Metformin
    2. Dipeptidyl peptidase-4 (DPP-4) inhibitor
    3. sodium glucose cotransporter 2 (SGLT2) inhibitor
    4. oral glucagon-like peptide 1 (GLP-1) agonist
  • Doses of OAMs are required to have been stable for at least 90 days prior to screening.
  • Participants may be treated with injectable GLP-1 receptor agonist for T2D in accordance with local regulations. The GLP-1 receptor agonist dose is required to have been stable for at least 90 days prior to screening.
  • Have an HbA1c value ≥7.5% and ≤10% according to the central laboratory at screening.

Exclusion criteria

Exclusion Criteria:

  • Have been diagnosed at any time with type 1 diabetes mellitus or latent autoimmune diabetes in adults.
  • Have had any episode of severe hypoglycemia (defined as requiring assistance due to neurologically disabling hypoglycemia) within 6 months prior to screening.
  • Have had any episode of hyperglycemic hyperosmolar state or diabetic ketoacidosis within 6 months prior to screening.
  • Have hypoglycemia unawareness as judged by the investigator.
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
187 participants (actual)

Study arms

  • Experimental
    LY900014

    LY900014 (100 units/milliliter (U/mL)) is a mealtime insulin administered subcutaneously (SC) 0-2 minutes prior to each meal in combination with insulin glargine (100 U/mL) SC as long-acting insulin. Mealtime (bolus) and long-acting (basal) insulin doses were titrated to achieve glucose targets during the study.

    Drug: LY900014 · Drug: Insulin Glargine

Interventions

  • DrugLY900014

    Administered SC

  • DrugInsulin Glargine

    Administered SC

06

What researchers measure

Primary outcomes

  1. Change From Baseline in Percentage of Time With Continuous Glucose Monitoring (CGM) Sensor Glucose Values Between 70-180 Milligrams/Deciliter (mg/dL) (3.9-10.0 Millimoles/Liter [mmol/L]) (Both Inclusive) During Daytime Period at Week 12

    Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with Baseline + Time as variables.

    Time frame: Baseline, Week 12

Secondary outcomes

  1. Change From Baseline in Hemoglobin A1c (HbA1c) at Week 12

    HbA1c is the glycosylated fraction of hemoglobin A. It is measured to identify average plasma glucose concentration over prolonged periods of time. LS mean was determined by MMRM model with Baseline + Time as variables.

    Time frame: Baseline, Week 12

  2. Change From Baseline in Percentage of Time With CGM Sensor Glucose Values Between 70-180 mg/dL (3.9-10.0 mmol/L) (Both Inclusive) During the 24-hour Period at Week 12

    LS mean was determined by MMRM model with Baseline + Time as variables.

    Time frame: Baseline, Week 12

  3. Change From Baseline in Percentage of Time With CGM Sensor Glucose Values <54 mg/dL (<3.0 mmol/L) During Daytime and 24-hour Periods at Week 12

    LS mean was determined by MMRM model with Baseline + Time as variables.

    Time frame: Baseline, Week 12

  4. Change From Baseline in Percentage of Time With CGM Sensor Glucose Values >180 mg/dL (>10.0 mmol/L) During Daytime and 24-hour Period at Week 12

    LS mean was determined by MMRM model with Baseline + Time as variables.

    Time frame: Baseline, Week 12

  5. Change From Baseline in Percentage of Time With CGM Sensor Glucose Value >250 mg/dL (>13.9 mmol/L) During Daytime and 24-hour Period at Week 12

    LS mean was determined by MMRM model with Baseline + Time as variables.

    Time frame: Baseline, Week 12

  6. Change From Baseline in Postprandial Incremental Area Under the Glucose Curve (iAUC) 0-1 Hour at Week 12

    iAUC reflects the metabolic control and is calculated using the standard trapezoidal rule from Glucose measures taken every 15 minutes from 0 to 1 hour after meal using CGM sensor (i.e., 0, 15, 30, 45, 60 minutes after meal). LS mean was determined by ANCOVA (analysis of covariance) with Baseline as covariate.

    Time frame: Baseline, Week 12

  7. Change From Baseline in Postprandial Incremental Area Under the Glucose Curve (iAUC) 0-2 Hour at Week 12

    iAUC reflects the metabolic control and is calculated using the standard trapezoidal rule from glucose measures taken every 15 minutes from 0 to 2 hours after meal using CGM sensor (i.e., 0, 15, 30, 45, 60, 75, 90, 105, 120 minutes after meal). LS mean was determined by ANCOVA (analysis of covariance) with Baseline as covariate.

    Time frame: Baseline, Week 12

  8. Percentage of Participants With HbA1c <7% and ≤6.5%

    HbA1c is the glycosylated fraction of hemoglobin A. It is measured to identify average plasma glucose concentration over prolonged periods of time.

    Time frame: Week 12

  9. Change From Baseline in Daily Insulin Dose at Week 12

    LS mean was determined by MMRM model with Baseline + Time as variables.

    Time frame: Baseline, Week 12

  10. Change From Baseline in Bolus/Total Insulin Dose Percentage at Week 12

    LS mean was determined by MMRM model with Baseline + Time as variables.

    Time frame: Baseline, Week 12

  11. Change From Baseline in Insulin Treatment Satisfaction Questionnaire (ITSQ) - Glycemic Control Domain Score at Week 12

    The ITSQ is a 22-item questionnaire that assesses treatment satisfaction for subjects taking insulin under 5 domains: Inconvenience of Regimen \[IR - 5 items\], Lifestyle Flexibility \[LF - 3 items\], Glycemic Control \[GC - 3 items\], Hypoglycemic Control \[HC - 5 items\], Insulin Delivery Device \[IDD - 6 items\]. Each Item is measured on a 7-point scale, with scores ranging for IR from 5 to 35, LF from 3 to 21, GC from 3 to 21, HC from 5 to 35, IDD from 6 to 42. Lower scores reflect better outcomes. Data presented are for Glycemic Control Domain Scores transformed on a 0-100 scale, where transformed domain score = 100×\[(7-raw domain score)/6\]. Higher scores indicate better glycemic control. Least squares (LS) mean estimated from analysis of covariance (ANCOVA) model that included baseline score as a covariate.

    Time frame: Baseline, Week 12

07

Results

Posted Mar 3, 2023

Participant flow

Participant flow — Overall Study
MilestoneLY900014
Started187
Received at least 1 dose of study drug176
Completed154
Not completed33
Withdrew: Adverse event5
Withdrew: Lack of efficacy1
Withdrew: Lost to follow-up8
Withdrew: Physician decision4
Withdrew: Withdrawal by subject14
Withdrew: Non-compliance with study1

Outcome measures

PrimaryChange From Baseline in Percentage of Time With Continuous Glucose Monitoring (CGM) Sensor Glucose Values Between 70-180 Milligrams/Deciliter (mg/dL) (3.9-10.0 Millimoles/Liter [mmol/L]) (Both Inclusive) During Daytime Period at Week 12

Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with Baseline + Time as variables.

Time frame:
Baseline, Week 12
Reported as:
Least squares mean · Percentage of time
Change From Baseline in Percentage of Time With Continuous Glucose Monitoring (CGM) Sensor Glucose Values Between 70-180 Milligrams/Deciliter (mg/dL) (3.9-10.0 Millimoles/Liter [mmol/L]) (Both Inclusive) During Daytime Period at Week 12
Percentage of timeLY900014
Change From Baseline in Percentage of Time With Continuous Glucose Monitoring (CGM) Sensor Glucose Values Between 70-180 Milligrams/Deciliter (mg/dL) (3.9-10.0 Millimoles/Liter [mmol/L]) (Both Inclusive) During Daytime Period at Week 123.8 ± 1.38
SecondaryChange From Baseline in Hemoglobin A1c (HbA1c) at Week 12

HbA1c is the glycosylated fraction of hemoglobin A. It is measured to identify average plasma glucose concentration over prolonged periods of time. LS mean was determined by MMRM model with Baseline + Time as variables.

Time frame:
Baseline, Week 12
Reported as:
Least squares mean · Percentage of HbA1c
Change From Baseline in Hemoglobin A1c (HbA1c) at Week 12
Percentage of HbA1cLY900014
Change From Baseline in Hemoglobin A1c (HbA1c) at Week 12-0.44 ± 0.069
SecondaryChange From Baseline in Percentage of Time With CGM Sensor Glucose Values Between 70-180 mg/dL (3.9-10.0 mmol/L) (Both Inclusive) During the 24-hour Period at Week 12

LS mean was determined by MMRM model with Baseline + Time as variables.

Time frame:
Baseline, Week 12
Reported as:
Least squares mean · Percentage of time
Change From Baseline in Percentage of Time With CGM Sensor Glucose Values Between 70-180 mg/dL (3.9-10.0 mmol/L) (Both Inclusive) During the 24-hour Period at Week 12
Percentage of timeLY900014
Change From Baseline in Percentage of Time With CGM Sensor Glucose Values Between 70-180 mg/dL (3.9-10.0 mmol/L) (Both Inclusive) During the 24-hour Period at Week 123.3 ± 1.37
SecondaryChange From Baseline in Percentage of Time With CGM Sensor Glucose Values <54 mg/dL (<3.0 mmol/L) During Daytime and 24-hour Periods at Week 12

LS mean was determined by MMRM model with Baseline + Time as variables.

Time frame:
Baseline, Week 12
Reported as:
Least squares mean · Percentage of time
Change From Baseline in Percentage of Time With CGM Sensor Glucose Values <54 mg/dL (<3.0 mmol/L) During Daytime and 24-hour Periods at Week 12
Percentage of timeLY900014
Daytime0.10 ± 0.117
24-hour Period0.00 ± 0.153
SecondaryChange From Baseline in Percentage of Time With CGM Sensor Glucose Values >180 mg/dL (>10.0 mmol/L) During Daytime and 24-hour Period at Week 12

LS mean was determined by MMRM model with Baseline + Time as variables.

Time frame:
Baseline, Week 12
Reported as:
Least squares mean · Percentage of time
Change From Baseline in Percentage of Time With CGM Sensor Glucose Values >180 mg/dL (>10.0 mmol/L) During Daytime and 24-hour Period at Week 12
Percentage of timeLY900014
Daytime-4.3 ± 1.49
24-Hour Period-3.4 ± 1.51
SecondaryChange From Baseline in Percentage of Time With CGM Sensor Glucose Value >250 mg/dL (>13.9 mmol/L) During Daytime and 24-hour Period at Week 12

LS mean was determined by MMRM model with Baseline + Time as variables.

Time frame:
Baseline, Week 12
Reported as:
Least squares mean · Percentage of time
Change From Baseline in Percentage of Time With CGM Sensor Glucose Value >250 mg/dL (>13.9 mmol/L) During Daytime and 24-hour Period at Week 12
Percentage of timeLY900014
Daytime-1.56 ± 0.773
24-Hour Period-1.07 ± 0.748
SecondaryChange From Baseline in Postprandial Incremental Area Under the Glucose Curve (iAUC) 0-1 Hour at Week 12

iAUC reflects the metabolic control and is calculated using the standard trapezoidal rule from Glucose measures taken every 15 minutes from 0 to 1 hour after meal using CGM sensor (i.e., 0, 15, 30, 45, 60 minutes after meal). LS mean was determined by ANCOVA (analysis of covariance) with Baseline as covariate.

Time frame:
Baseline, Week 12
Reported as:
Least squares mean · milligrams*hours per deciliter (mg*h/dl)
Change From Baseline in Postprandial Incremental Area Under the Glucose Curve (iAUC) 0-1 Hour at Week 12
milligrams*hours per deciliter (mg*h/dl)LY900014
Breakfast-1.57 ± 1.191
Lunch-0.56 ± 1.205
Dinner-2.76 ± 1.287
Overall - across meals-2.46 ± 0.856
SecondaryChange From Baseline in Postprandial Incremental Area Under the Glucose Curve (iAUC) 0-2 Hour at Week 12

iAUC reflects the metabolic control and is calculated using the standard trapezoidal rule from glucose measures taken every 15 minutes from 0 to 2 hours after meal using CGM sensor (i.e., 0, 15, 30, 45, 60, 75, 90, 105, 120 minutes after meal). LS mean was determined by ANCOVA (analysis of covariance) with Baseline as covariate.

Time frame:
Baseline, Week 12
Reported as:
Least squares mean · mg*h/dl
Change From Baseline in Postprandial Incremental Area Under the Glucose Curve (iAUC) 0-2 Hour at Week 12
mg*h/dlLY900014
Breakfast-8.1 ± 3.78
Lunch-2.57 ± 3.652
Dinner-8.32 ± 3.933
Overall - across meals-8.8 ± 2.47
SecondaryPercentage of Participants With HbA1c <7% and ≤6.5%

HbA1c is the glycosylated fraction of hemoglobin A. It is measured to identify average plasma glucose concentration over prolonged periods of time.

Time frame:
Week 12
Reported as:
Number · Percentage of participants
Percentage of Participants With HbA1c <7% and ≤6.5%
Percentage of participantsLY900014
HbA1c <7%16.88
HbA1c ≤6.5%4.55
SecondaryChange From Baseline in Daily Insulin Dose at Week 12

LS mean was determined by MMRM model with Baseline + Time as variables.

Time frame:
Baseline, Week 12
Reported as:
Least squares mean · Units per day
Change From Baseline in Daily Insulin Dose at Week 12
Units per dayLY900014
Basal Insulin Dose3.7 ± 1.29
Bolus Insulin Dose18.0 ± 2.53
Total Insulin Dose22.0 ± 3.26
SecondaryChange From Baseline in Bolus/Total Insulin Dose Percentage at Week 12

LS mean was determined by MMRM model with Baseline + Time as variables.

Time frame:
Baseline, Week 12
Reported as:
Least squares mean · percentage of insulin dose
Change From Baseline in Bolus/Total Insulin Dose Percentage at Week 12
percentage of insulin doseLY900014
Change From Baseline in Bolus/Total Insulin Dose Percentage at Week 126.0 ± 0.97
SecondaryChange From Baseline in Insulin Treatment Satisfaction Questionnaire (ITSQ) - Glycemic Control Domain Score at Week 12

The ITSQ is a 22-item questionnaire that assesses treatment satisfaction for subjects taking insulin under 5 domains: Inconvenience of Regimen \[IR - 5 items\], Lifestyle Flexibility \[LF - 3 items\], Glycemic Control \[GC - 3 items\], Hypoglycemic Control \[HC - 5 items\], Insulin Delivery Device \[IDD - 6 items\]. Each Item is measured on a 7-point scale, with scores ranging for IR from 5 to 35, LF from 3 to 21, GC from 3 to 21, HC from 5 to 35, IDD from 6 to 42. Lower scores reflect better outcomes. Data presented are for Glycemic Control Domain Scores transformed on a 0-100 scale, where transformed domain score = 100×\[(7-raw domain score)/6\]. Higher scores indicate better glycemic control. Least squares (LS) mean estimated from analysis of covariance (ANCOVA) model that included baseline score as a covariate.

Time frame:
Baseline, Week 12
Reported as:
Least squares mean · score on a scale
Change From Baseline in Insulin Treatment Satisfaction Questionnaire (ITSQ) - Glycemic Control Domain Score at Week 12
score on a scaleLY900014
Change From Baseline in Insulin Treatment Satisfaction Questionnaire (ITSQ) - Glycemic Control Domain Score at Week 1216.9 ± 1.55

Adverse events

Collected over Baseline to Follow-up (Up To 14 weeks). Non-serious events are listed at a 3% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
LY9000140/176 (0%)3/176 (1.7%)0/176 (0%)
Most frequent serious events
Most frequent serious events
EventLY900014
Iron deficiency anaemiaBlood and lymphatic system disorders1/176
VertigoEar and labyrinth disorders1/176
Covid-19Infections and infestations1/176

Baseline characteristics

All enrolled participants.

Age, Continuous
Age, Continuous(years)LY900014
Mean62.6 ± 10.3
Sex: Female, Male
Sex: Female, Male(Participants)LY900014
Female82
Male105
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)LY900014
Hispanic or Latino58
Not Hispanic or Latino129
Unknown or Not Reported0
Race (NIH/OMB)
Race (NIH/OMB)(Participants)LY900014
American Indian or Alaska Native4
Asian16
Native Hawaiian or Other Pacific Islander0
Black or African American23
White140
More than one race3
Unknown or Not Reported1
Region of Enrollment
Region of Enrollment(Participants)LY900014
United States187
Percentage of Time With Sensor Glucose Values Between 70 and 180 mg/dL During Daytime Period
Percentage of Time With Sensor Glucose Values Between 70 and 180 mg/dL During Daytime Period(Percentage of time)LY900014
Mean58.65 ± 15.99
08

Study locations

32 sites
  • John Muir Physician Network Clinical Research Center
    Concord, California 94520, United States
  • AMCR Institute
    Escondido, California 92025, United States
  • Valley Endocrine, Fresno
    Fresno, California 93720, United States
  • University Clinical Investigators, Inc.
    Tustin, California 92780, United States
  • Coastal Metabolic Research Centre
    Ventura, California 93003, United States
  • CMR of Greater New Haven
    Hamden, Connecticut 06517, United States
  • Encore Medical Research
    Hollywood, Florida 33021, United States
  • Sun Coast Clinical Research, Inc
    New Port Richey, Florida 34652, United States
  • Metabolic Research Institute, Inc.
    West Palm Beach, Florida 33401, United States
  • Atlanta Diabetes Associates
    Atlanta, Georgia 30318, United States
  • East Coast Institute for Research at The Jones Center
    Macon, Georgia 31210, United States
  • Rocky Mountain Clinical Research
    Idaho Falls, Idaho 83404, United States
  • Central Illinois Diabetes and Clinical Research a Division of Prairie Education and Research Cooperative
    Springfield, Illinois 62711, United States
  • Iowa Diabetes and Endocrinology Research Center
    West Des Moines, Iowa 50265, United States
  • Maryland Cardiovascular Specialists
    Baltimore, Maryland 21229, United States
  • Endocrine and Metabolic Consultants
    Rockville, Maryland 20852, United States
  • Palm Research Center Tenaya
    Las Vegas, Nevada 89128, United States
  • Palm Research Center Tenaya
    Las Vegas, Nevada 89148, United States
  • Research NYC, Inc
    New York, New York 10016, United States
  • Suny Health Science Center at Syracuse
    Syracuse, New York 13210, United States
  • Cataret Medical Group
    Morehead City, North Carolina 28557, United States
  • Intend Research, LLC
    Norman, Oklahoma 73069, United States
  • Texas Diabetes & Endocrinology, P.A.
    Austin, Texas 78749, United States
  • Dallas Diabetes Research Center
    Dallas, Texas 75230, United States
  • Biopharma Informatic, LLC
    Houston, Texas 77043, United States
  • Endocrine Ips, Pllc
    Houston, Texas 77079, United States
  • Consano Clinical Research, LLC
    Shavano Park, Texas 78231, United States
  • Burke Internal Medicine and Research
    Burke, Virginia 22015, United States
  • Manassas Clinical Research Center
    Manassas, Virginia 20110, United States
  • Rainier Clinical Research Center
    Renton, Washington 98057, United States
  • Advanced Clinical Research, LLC
    Bayamon, 00961, Puerto Rico
  • Manati Center for Clinical Research Inc
    Manati, 00674, Puerto Rico
09

References and documents

Study documents

  • Study protocol · Jul 13, 2020
  • Statistical analysis plan · Oct 27, 2020

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.

Supporting information: Study protocol, Sap, Csr

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Mar 3, 2023, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT04605991
Lead sponsor
Eli Lilly and Company
Responsible party
Sponsor
First posted
Oct 28, 2020
Start date
Nov 4, 2020
Primary completion
Feb 4, 2022
Completion
Feb 4, 2022
Results posted
Mar 3, 2023
Last update
Mar 3, 2023

Study contacts

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
study director · Eli Lilly and Company

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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