Type 2 Diabetes
Conditions
Brief 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.
Interventions
DRUGLY900014
Administered SC
DRUGInsulin Glargine
Administered SC
Sponsors
Eli Lilly and Company
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Baseline, Week 12 | Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with Baseline + Time as variables. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Baseline, Week 12 | LS mean was determined by MMRM model with Baseline + Time as variables. |
| 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 | Baseline, Week 12 | LS mean was determined by MMRM model with Baseline + Time as variables. |
| 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 | Baseline, Week 12 | LS mean was determined by MMRM model with Baseline + Time as variables. |
| 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 | Baseline, Week 12 | LS mean was determined by MMRM model with Baseline + Time as variables. |
| Change From Baseline in Postprandial Incremental Area Under the Glucose Curve (iAUC) 0-1 Hour at Week 12 | Baseline, 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. |
| Change From Baseline in Hemoglobin A1c (HbA1c) at Week 12 | Baseline, 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. |
| Percentage of Participants With HbA1c <7% and ≤6.5% | Week 12 | HbA1c is the glycosylated fraction of hemoglobin A. It is measured to identify average plasma glucose concentration over prolonged periods of time. |
| Change From Baseline in Daily Insulin Dose at Week 12 | Baseline, Week 12 | LS mean was determined by MMRM model with Baseline + Time as variables. |
| Change From Baseline in Bolus/Total Insulin Dose Percentage at Week 12 | Baseline, Week 12 | LS mean was determined by MMRM model with Baseline + Time as variables. |
| Change From Baseline in Insulin Treatment Satisfaction Questionnaire (ITSQ) - Glycemic Control Domain Score at Week 12 | Baseline, 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. |
| Change From Baseline in Postprandial Incremental Area Under the Glucose Curve (iAUC) 0-2 Hour at Week 12 | Baseline, 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. |
Countries
Puerto Rico, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| LY900014 LY900014 (100 U/mL) is a mealtime insulin administered 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. | 187 |
| Total | 187 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 5 |
| Overall Study | Lack of Efficacy | 1 |
| Overall Study | Lost to Follow-up | 8 |
| Overall Study | Non-compliance with study | 1 |
| Overall Study | Physician Decision | 4 |
| Overall Study | Withdrawal by Subject | 14 |
Baseline characteristics
| Characteristic | LY900014 |
|---|---|
| Age, Continuous | 62.6 years STANDARD_DEVIATION 10.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 58 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 129 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Percentage of Time With Sensor Glucose Values Between 70 and 180 mg/dL During Daytime Period | 58.65 Percentage of time STANDARD_DEVIATION 15.99 |
| Race (NIH/OMB) American Indian or Alaska Native | 4 Participants |
| Race (NIH/OMB) Asian | 16 Participants |
| Race (NIH/OMB) Black or African American | 23 Participants |
| Race (NIH/OMB) More than one race | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 140 Participants |
| Region of Enrollment United States | 187 Participants |
| Sex: Female, Male Female | 82 Participants |
| Sex: Female, Male Male | 105 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 176 |
| other Total, other adverse events | 0 / 176 |
| serious Total, serious adverse events | 3 / 176 |
Outcome results
Primary
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
Population: All participants who received at least one dose of study drug and had baseline, post-baseline CGM glucose values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| LY900014 | 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 | 3.8 Percentage of time | Standard Error 1.38 |
Secondary
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
Population: All participants who received at least one dose of study drug and had baseline, post-baseline values for bolus and total insulin dose.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| LY900014 | Change From Baseline in Bolus/Total Insulin Dose Percentage at Week 12 | 6.0 percentage of insulin dose | Standard Error 0.97 |
Secondary
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
Population: All participants who received at least one dose of study drug and had baseline, post-baseline insulin dose data.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| LY900014 | Change From Baseline in Daily Insulin Dose at Week 12 | Basal Insulin Dose | 3.7 Units per day | Standard Error 1.29 |
| LY900014 | Change From Baseline in Daily Insulin Dose at Week 12 | Bolus Insulin Dose | 18.0 Units per day | Standard Error 2.53 |
| LY900014 | Change From Baseline in Daily Insulin Dose at Week 12 | Total Insulin Dose | 22.0 Units per day | Standard Error 3.26 |
Secondary
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
Population: All participants who received at least one dose of study drug and had baseline, post-baseline HbA1c values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| LY900014 | Change From Baseline in Hemoglobin A1c (HbA1c) at Week 12 | -0.44 Percentage of HbA1c | Standard Error 0.069 |
Secondary
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
Population: All participants who received at least one dose of study drug and had baseline, post-baseline ITSQ data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| LY900014 | Change From Baseline in Insulin Treatment Satisfaction Questionnaire (ITSQ) - Glycemic Control Domain Score at Week 12 | 16.9 score on a scale | Standard Error 1.55 |
Secondary
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
Population: All participants who received at least one dose of study drug and had baseline, post-baseline CGM glucose values.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| LY900014 | 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 | Daytime | -1.56 Percentage of time | Standard Error 0.773 |
| LY900014 | 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 | 24-Hour Period | -1.07 Percentage of time | Standard Error 0.748 |
Secondary
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
Population: All participants who received at least one dose of study drug and had baseline, post-baseline CGM glucose values.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| LY900014 | 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 | Daytime | -4.3 Percentage of time | Standard Error 1.49 |
| LY900014 | 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 | 24-Hour Period | -3.4 Percentage of time | Standard Error 1.51 |
Secondary
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
Population: All participants who received at least one dose of study drug and had baseline, post-baseline CGM glucose values.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| LY900014 | 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 | Daytime | 0.10 Percentage of time | Standard Error 0.117 |
| LY900014 | 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 | 24-hour Period | 0.00 Percentage of time | Standard Error 0.153 |
Secondary
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
Population: All participants who received at least one dose of study drug and had baseline, post-baseline CGM glucose values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| LY900014 | 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 | 3.3 Percentage of time | Standard Error 1.37 |
Secondary
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
Population: All participants who received at least one dose of study drug and had baseline, post-baseline iAUC data.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| LY900014 | Change From Baseline in Postprandial Incremental Area Under the Glucose Curve (iAUC) 0-1 Hour at Week 12 | Lunch | -0.56 milligrams*hours per deciliter (mg*h/dl) | Standard Error 1.205 |
| LY900014 | Change From Baseline in Postprandial Incremental Area Under the Glucose Curve (iAUC) 0-1 Hour at Week 12 | Breakfast | -1.57 milligrams*hours per deciliter (mg*h/dl) | Standard Error 1.191 |
| LY900014 | Change From Baseline in Postprandial Incremental Area Under the Glucose Curve (iAUC) 0-1 Hour at Week 12 | Dinner | -2.76 milligrams*hours per deciliter (mg*h/dl) | Standard Error 1.287 |
| LY900014 | Change From Baseline in Postprandial Incremental Area Under the Glucose Curve (iAUC) 0-1 Hour at Week 12 | Overall - across meals | -2.46 milligrams*hours per deciliter (mg*h/dl) | Standard Error 0.856 |
Secondary
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
Population: All participants who received at least one dose of study drug and had baseline, post-baseline iAUC data.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| LY900014 | Change From Baseline in Postprandial Incremental Area Under the Glucose Curve (iAUC) 0-2 Hour at Week 12 | Breakfast | -8.1 mg*h/dl | Standard Error 3.78 |
| LY900014 | Change From Baseline in Postprandial Incremental Area Under the Glucose Curve (iAUC) 0-2 Hour at Week 12 | Lunch | -2.57 mg*h/dl | Standard Error 3.652 |
| LY900014 | Change From Baseline in Postprandial Incremental Area Under the Glucose Curve (iAUC) 0-2 Hour at Week 12 | Dinner | -8.32 mg*h/dl | Standard Error 3.933 |
| LY900014 | Change From Baseline in Postprandial Incremental Area Under the Glucose Curve (iAUC) 0-2 Hour at Week 12 | Overall - across meals | -8.8 mg*h/dl | Standard Error 2.47 |
Secondary
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
Population: All participants who received at least one dose of study drug and had post-baseline HbA1c values.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LY900014 | Percentage of Participants With HbA1c <7% and ≤6.5% | HbA1c <7% | 16.88 Percentage of participants |
| LY900014 | Percentage of Participants With HbA1c <7% and ≤6.5% | HbA1c ≤6.5% | 4.55 Percentage of participants |