Trial Outcomes & Findings for A Study of Mealtime Insulin LY900014 in Participants With Type 2 Diabetes Using Continuous Glucose Monitoring (PRONTO-Time in Range) (NCT NCT04605991)

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

187 participants

Primary outcome timeframe

Baseline, Week 12

Results posted on

2023-03-03

Participant Flow

Participant milestones

Participant milestones
Measure	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.
Overall Study STARTED	187
Overall Study Received at Least 1 Dose of Study Drug	176
Overall Study COMPLETED	154
Overall Study NOT COMPLETED	33

Reasons for withdrawal

Reasons for withdrawal
Measure	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.
Overall Study Adverse Event	5
Overall Study Lack of Efficacy	1
Overall Study Lost to Follow-up	8
Overall Study Physician Decision	4
Overall Study Withdrawal by Subject	14
Overall Study Non-compliance with study	1

Baseline Characteristics

All participants who received at least one dose of study drug and had baseline CGM glucose values.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	LY900014 n=187 Participants 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.
Age, Continuous	62.6 years STANDARD_DEVIATION 10.3 • n=187 Participants
Sex: Female, Male Female	82 Participants n=187 Participants
Sex: Female, Male Male	105 Participants n=187 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	58 Participants n=187 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	129 Participants n=187 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=187 Participants
Race (NIH/OMB) American Indian or Alaska Native	4 Participants n=187 Participants
Race (NIH/OMB) Asian	16 Participants n=187 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=187 Participants
Race (NIH/OMB) Black or African American	23 Participants n=187 Participants
Race (NIH/OMB) White	140 Participants n=187 Participants
Race (NIH/OMB) More than one race	3 Participants n=187 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=187 Participants
Region of Enrollment United States	187 Participants n=187 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 • n=163 Participants • All participants who received at least one dose of study drug and had baseline CGM glucose values.

PRIMARY outcome

Timeframe: Baseline, Week 12

Population: All participants who received at least one dose of study drug and had baseline, post-baseline CGM glucose values.

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

Outcome measures

Outcome measures
Measure	LY900014 n=153 Participants 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.
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 outcome

Timeframe: Baseline, Week 12

Population: All participants who received at least one dose of study drug and had baseline, post-baseline HbA1c values.

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.

Outcome measures

Outcome measures
Measure	LY900014 n=167 Participants 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.
Change From Baseline in Hemoglobin A1c (HbA1c) at Week 12	-0.44 Percentage of HbA1c Standard Error 0.069

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: All participants who received at least one dose of study drug and had baseline, post-baseline CGM glucose values.

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

Outcome measures

Outcome measures
Measure	LY900014 n=153 Participants 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.
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 outcome

Timeframe: Baseline, Week 12

Population: All participants who received at least one dose of study drug and had baseline, post-baseline CGM glucose values.

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

Outcome measures

Outcome measures
Measure	LY900014 n=153 Participants 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.
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
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 outcome

Timeframe: Baseline, Week 12

Population: All participants who received at least one dose of study drug and had baseline, post-baseline CGM glucose values.

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

Outcome measures

Outcome measures
Measure	LY900014 n=153 Participants 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.
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
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 outcome

Timeframe: Baseline, Week 12

Population: All participants who received at least one dose of study drug and had baseline, post-baseline CGM glucose values.

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

Outcome measures

Outcome measures
Measure	LY900014 n=153 Participants 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.
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
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 outcome

Timeframe: Baseline, Week 12

Population: All participants who received at least one dose of study drug and had baseline, post-baseline iAUC data.

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.

Outcome measures

Outcome measures
Measure	LY900014 n=111 Participants 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.
Change From Baseline in Postprandial Incremental Area Under the Glucose Curve (iAUC) 0-1 Hour at Week 12 Breakfast	-1.57 milligramshours per deciliter (mgh/dl) Standard Error 1.191
Change From Baseline in Postprandial Incremental Area Under the Glucose Curve (iAUC) 0-1 Hour at Week 12 Lunch	-0.56 milligramshours per deciliter (mgh/dl) Standard Error 1.205
Change From Baseline in Postprandial Incremental Area Under the Glucose Curve (iAUC) 0-1 Hour at Week 12 Dinner	-2.76 milligramshours per deciliter (mgh/dl) Standard Error 1.287
Change From Baseline in Postprandial Incremental Area Under the Glucose Curve (iAUC) 0-1 Hour at Week 12 Overall - across meals	-2.46 milligramshours per deciliter (mgh/dl) Standard Error 0.856

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: All participants who received at least one dose of study drug and had baseline, post-baseline iAUC data.

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.

Outcome measures

Outcome measures
Measure	LY900014 n=111 Participants 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.
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
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
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
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 outcome

Timeframe: Week 12

Population: All participants who received at least one dose of study drug and had post-baseline HbA1c values.

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

Outcome measures

Outcome measures
Measure	LY900014 n=154 Participants 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.
Percentage of Participants With HbA1c <7% and ≤6.5% HbA1c <7%	16.88 Percentage of participants
Percentage of Participants With HbA1c <7% and ≤6.5% HbA1c ≤6.5%	4.55 Percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: All participants who received at least one dose of study drug and had baseline, post-baseline insulin dose data.

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

Outcome measures

Outcome measures
Measure	LY900014 n=155 Participants 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.
Change From Baseline in Daily Insulin Dose at Week 12 Basal Insulin Dose	3.7 Units per day Standard Error 1.29
Change From Baseline in Daily Insulin Dose at Week 12 Bolus Insulin Dose	18.0 Units per day Standard Error 2.53
Change From Baseline in Daily Insulin Dose at Week 12 Total Insulin Dose	22.0 Units per day Standard Error 3.26

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure	LY900014 n=154 Participants 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.
Change From Baseline in Bolus/Total Insulin Dose Percentage at Week 12	6.0 percentage of insulin dose Standard Error 0.97

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: All participants who received at least one dose of study drug and had baseline, post-baseline ITSQ data.

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.

Outcome measures

Outcome measures
Measure	LY900014 n=160 Participants 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.
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

Adverse Events

LY900014

Serious events: 3 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	LY900014 n=176 participants at risk 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.
Blood and lymphatic system disorders Iron deficiency anaemia	0.57% 1/176 • Number of events 1 • Baseline to Follow-up (Up To 14 weeks) All participants who received at least one dose of study drug.
Ear and labyrinth disorders Vertigo	0.57% 1/176 • Number of events 1 • Baseline to Follow-up (Up To 14 weeks) All participants who received at least one dose of study drug.
Infections and infestations Covid-19	0.57% 1/176 • Number of events 1 • Baseline to Follow-up (Up To 14 weeks) All participants who received at least one dose of study drug.

Other adverse events

Adverse event data not reported

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60