Type 2 Diabetes Mellitus
Conditions
Brief summary
The purpose of this study is to compare LY900014 to insulin lispro, both in combination with insulin glargine or insulin degludec, in participants with type 2 diabetes (T2D).
Interventions
DRUGLY900014
Administered SC
DRUGInsulin Lispro
Administered SC
DRUGInsulin Glargine
Administered SC
DRUGInsulin Degludec
Administered SC
DRUGMetformin
Administered orally.
DRUGSGLT2 inhibitor
Administered orally.
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have been diagnosed (clinically) with T2D, based on the World Health Organization (WHO) classification for at least 1 year prior to screening. * Have been treated for at least 90 days prior to screening with: * Basal insulin (insulin glargine U-100 \[Basaglar/Abasaglar or LANTUS\] or U-300, insulin detemir, insulin degludec U-100 or U-200, or neutral protamine Hagedorn \[NPH\] insulin) in combination with at least 1 prandial injection of bolus insulin (insulin lispro U-100 or U-200, insulin aspart, insulin glulisine, or regular insulin) Or * Premixed analog or human insulin regimens with any basal and bolus insulin combination injected at least twice daily * Participants may be treated with up to 3 of the following oral antihyperglycemic medications (OAMs) in accordance with local regulations: * Metformin * Dipeptidyl peptidase-4 (DPP-4) inhibitor * Sodium glucose cotransporter 2 (SGLT2) inhibitor * Sulfonylurea * Meglitinide * Alpha-glucoside inhibitor * Have an HbA1c value between ≥7.0 and ≤10.0%, according to the central laboratory at the time of screening. * Have a body mass index (BMI) of ≤45.0 kilograms per meter squared at screening.
Exclusion criteria
* Have been diagnosed, at any time, with type 1 diabetes (T1D) or Latent Autoimmune Diabetes in Adults. * Have hypoglycemia unawareness as judged by the investigator. * Have had any episode of severe hypoglycemia within the 6 months prior to screening. * Have had 1 or more episodes of diabetic ketoacidosis or hyperglycemic hyperosmolar state within the 6 months prior to screening. * Have used thiazolidinediones, Glucagon-Like Peptide 1 (GLP-1) receptor agonist, or pramlintide within 90 days prior to screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Hemoglobin A1c (HbA1c) Efficacy Estimand at Week 26 | Baseline, Week 26 | Change from baseline in HbA1c was performed using mixed model repeated measures (MMRM) including fixed class effects of treatment, strata (pooled country, type of basal insulin, and number of prandial doses at study entry), visit, and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline value. The efficacy estimand included participant data when baseline and at least one post-baseline measurement were available prior to permanent discontinuation of study drug. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 2-hour PPG Excursion During MMTT Efficacy Estimand | Week 26 | 2-hour PPG excursion during MMTT uses the ANCOVA model with strata (pooled country, type of basal insulin, number of prandial doses at study entry, and HbA1c stratum) and treatment as fixed effects and baseline as a covariate. The efficacy estimand included participant data when baseline and at least one post-baseline measurement were available prior to permanent discontinuation of study drug. |
| Rate of Severe Hypoglycemia | Baseline through Week 26 | Rate of severe hypoglycemia events per 100 years during a defined period was calculated by total number of severe hypoglycemia episodes within the period divided by the cumulative days on treatment from all participants within a treatment group \*36525. Severe hypoglycemia is defined as an event requiring assistance of another person to administer carbohydrate, glucagon, or other resuscitative actions. During these episodes, the participant has an altered mental status and cannot assist in his or her own care, or may be semiconscious or unconscious, or experience com with or without seizures, and may require parenteral therapy. |
| Rate of Documented Symptomatic Hypoglycemia | Baseline through Week 26 | Documented symptomatic hypoglycemia is an event during which typical symptoms of hypoglycemia are accompanied by blood glucose (BG) of \<54 mg/dL \[3.0 millimole per liter (mmol/L)\]. The rate of documented symptomatic hypoglycemia was estimated by negative binomial model: number of episodes = treatment with log (treatment exposure in days/365.25) as an offset variable. |
| Change From Baseline in 1,5-Anhydroglucitol (1,5-AG) at Week 26 | Baseline, Week 26 | Change from baseline in 1,5-AG was analyzed using mixed model repeated measures (MMRM) including fixed class effects of treatment, strata (pooled country, type of basal insulin, HbA1c stratum and number of prandial doses at study entry), visit, and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline value. The analysis included data collected prior to permanent discontinuation of study drug. |
| 1-hour Postprandial Glucose (PPG) Excursion During Mixed-Meal Tolerance Test (MMTT) Efficacy Estimand | Week 26 | 1-hour PPG excursion during MMTT uses the analysis of covariance (ANCOVA) model with strata (pooled country, type of basal insulin, number of prandial doses at study entry, and HbA1c stratum) and treatment as fixed effects and baseline as a covariate. The efficacy estimand included participant data when baseline and at least one post-baseline measurement were available prior to permanent discontinuation of study drug. |
| Change From Baseline in Insulin Dose at Week 26 | Baseline, Week 26 | Change from baseline in insulin dose was analyzed using mixed model repeated measures (MMRM) including fixed class effects of treatment, strata (pooled country, type of basal insulin, HbA1c stratum and number of prandial doses at study entry), visit, and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline value. The analysis included data prior to permanent discontinuation of study drug. |
| Change From Baseline in Insulin Treatment Satisfaction Questionnaire (ITSQ) Regimen Inconvenience Domain Score at Week 26 | Baseline, Week 26 | ITSQ is a validated instrument containing 22 items that assess treatment satisfaction for participants with diabetes and on insulin. The questionnaire measures satisfaction from the following 5 domains: Inconvenience of Regimen, Lifestyle Flexibility, Glycemic Control, Hypoglycemic Control, and Insulin Delivery Device. Data presented are the transformed overall score on a scale of 0-100, where higher scores indicate better treatment satisfaction. Change from baseline in ITSQ regimen inconvenience domain score was calculated using the ANCOVA model with strata (pooled country, type of basal insulin, number of prandial doses at study entry, and HbA1c stratum), and treatment as fixed effects and baseline as covariate. The analysis included data prior to permanent discontinuation of study drug. |
| Change From Baseline in ITSQ Lifestyle Flexibility Domain Score at Week 26 | Baseline, Week 26 | ITSQ is a validated instrument containing 22 items that assess treatment satisfaction for participants with diabetes and on insulin. The questionnaire measures satisfaction from the following 5 domains: Inconvenience of Regimen, Lifestyle Flexibility, Glycemic Control, Hypoglycemic Control, and Insulin Delivery Device. Data presented are the transformed overall score on a scale of 0-100, where higher scores indicate better treatment satisfaction. Change from baseline in ITSQ lifestyle flexibility domain score was calculated using the ANCOVA model with strata (pooled country, type of basal insulin, number of prandial doses at study entry, and HbA1c stratum), and treatment as fixed effects and baseline as covariate. The analysis included data prior to permanent discontinuation of study drug. |
| Number of Participants With HbA1c <7% | Week 26 | Number of participants with HbA1c \<7% at Week 26. |
| Change From Baseline in 10-Point Self-Monitoring Blood Glucose (SMBG) Values at Week 26 | Baseline, Week 26 | Change from baseline in 10-point SMBG values was analyzed using mixed model repeated measures (MMRM) including fixed class effects of treatment, strata (pooled country, type of basal insulin, HbA1c stratum and number of prandial doses at study entry), visit, and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline value. The efficacy estimand included participant data when baseline and at least one post-baseline measurement prior to permanent discontinuation of study drug. |
Countries
Argentina, Australia, Czechia, Germany, Hungary, India, Italy, Japan, Mexico, Puerto Rico, Russia, Slovakia, South Korea, Spain, Taiwan, United States
Participant flow
Pre-assignment details
The purpose of the Lead-in Period was to titrate basal insulin prior to randomization. Participants were then randomized to receive Insulin lispro (Humalog) or LY900014 in the Treatment Period (Period 2).
Participants by arm
| Arm | Count |
|---|---|
| Insulin Lispro (Humalog) Insulin lispro given SC with each meal with either U-100 basal insulin glargine given SC once or twice daily or U-100 or U-200 insulin degludec given SC once daily. Prandial insulin doses were individualized and titrated according to protocol-defined targets. | 337 |
| LY900014 LY900014 given subcutaneously (SC) with each meal with either 100 U/mL (U-100) basal insulin glargine given SC once or twice daily or U-100 or 200 U/mL (U-200) insulin degludec given SC once daily. Prandial insulin doses were individualized and titrated according to protocol-defined targets. | 336 |
| Insulin Lispro (Humalog) MEE Insulin lispro given SC with each meal with either U-100 basal insulin glargine given SC once or twice daily or U-100 or U-200 insulin degludec given SC once daily. Prandial insulin doses were individualized and titrated according to protocol-defined targets. | 82 |
| LY900014 Maximum Extended Enrollment (MEE) LY900014 given subcutaneously (SC) with each meal with either U-100 basal insulin glargine given SC once or twice daily or U-100 or U-200 insulin degludec given SC once daily. Prandial insulin doses were individualized and titrated according to protocol-defined targets. | 82 |
| Total | 837 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Lead-in | Adverse Event | 3 | 0 | 0 | 1 | 0 | 0 |
| Lead-in | Eligibility Criteria | 3 | 0 | 0 | 0 | 0 | 0 |
| Lead-in | Family Emergency | 1 | 0 | 0 | 0 | 0 | 0 |
| Lead-in | Lost to Follow-up | 4 | 0 | 0 | 1 | 0 | 0 |
| Lead-in | Natural Disaster | 9 | 0 | 0 | 0 | 0 | 0 |
| Lead-in | Non Compliance | 1 | 0 | 0 | 0 | 0 | 0 |
| Lead-in | Participant Schedule | 2 | 0 | 0 | 0 | 0 | 0 |
| Lead-in | Physician Decision | 6 | 0 | 0 | 0 | 0 | 0 |
| Lead-in | Protocol Deviation | 7 | 0 | 0 | 3 | 0 | 0 |
| Lead-in | Withdrawal by Subject | 41 | 0 | 0 | 14 | 0 | 0 |
| Treatment Period | Adverse Event | 0 | 1 | 1 | 0 | 1 | 0 |
| Treatment Period | Death | 0 | 1 | 2 | 0 | 0 | 0 |
| Treatment Period | Lost to Follow-up | 0 | 6 | 3 | 0 | 0 | 0 |
| Treatment Period | Non-Compliance with Study Drug | 0 | 0 | 0 | 0 | 1 | 0 |
| Treatment Period | Participant schedule | 0 | 0 | 1 | 0 | 0 | 0 |
| Treatment Period | Treatment Interruption | 0 | 0 | 1 | 0 | 0 | 0 |
| Treatment Period | Withdrawal by Subject | 0 | 10 | 8 | 0 | 7 | 11 |
Baseline characteristics
| Characteristic | Insulin Lispro (Humalog) | Total | LY900014 Maximum Extended Enrollment (MEE) | Insulin Lispro (Humalog) MEE | LY900014 |
|---|---|---|---|---|---|
| Age, Continuous | 61.0 years STANDARD_DEVIATION 9.2 | 59.9 years STANDARD_DEVIATION 9.5 | 57.2 years STANDARD_DEVIATION 10.1 | 56.6 years STANDARD_DEVIATION 9.4 | 60.2 years STANDARD_DEVIATION 9.4 |
| Hemoglobin A1c | 7.31 percentage of HbA1c STANDARD_DEVIATION 0.71 | 7.35 percentage of HbA1c STANDARD_DEVIATION 0.73 | 7.67 percentage of HbA1c STANDARD_DEVIATION 0.89 | 7.53 percentage of HbA1c STANDARD_DEVIATION 0.69 | 7.27 percentage of HbA1c STANDARD_DEVIATION 0.68 |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants | 4 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 81 Participants | 303 Participants | 69 Participants | 70 Participants | 83 Participants |
| Race (NIH/OMB) Black or African American | 16 Participants | 30 Participants | 0 Participants | 0 Participants | 14 Participants |
| Race (NIH/OMB) More than one race | 6 Participants | 11 Participants | 0 Participants | 0 Participants | 5 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 229 Participants | 487 Participants | 13 Participants | 12 Participants | 233 Participants |
| Region of Enrollment Argentina | 29 Participants | 56 Participants | 0 Participants | 0 Participants | 27 Participants |
| Region of Enrollment Australia | 7 Participants | 15 Participants | 0 Participants | 0 Participants | 8 Participants |
| Region of Enrollment Czechia | 20 Participants | 40 Participants | 0 Participants | 0 Participants | 20 Participants |
| Region of Enrollment Germany | 19 Participants | 40 Participants | 0 Participants | 0 Participants | 21 Participants |
| Region of Enrollment Hungary | 13 Participants | 28 Participants | 0 Participants | 0 Participants | 15 Participants |
| Region of Enrollment India | 9 Participants | 100 Participants | 44 Participants | 40 Participants | 7 Participants |
| Region of Enrollment Italy | 4 Participants | 9 Participants | 0 Participants | 0 Participants | 5 Participants |
| Region of Enrollment Japan | 46 Participants | 93 Participants | 0 Participants | 0 Participants | 47 Participants |
| Region of Enrollment Mexico | 21 Participants | 45 Participants | 1 Participants | 1 Participants | 22 Participants |
| Region of Enrollment Puerto Rico | 7 Participants | 14 Participants | 0 Participants | 0 Participants | 7 Participants |
| Region of Enrollment Russia | 14 Participants | 50 Participants | 12 Participants | 11 Participants | 13 Participants |
| Region of Enrollment Slovakia | 14 Participants | 28 Participants | 0 Participants | 0 Participants | 14 Participants |
| Region of Enrollment South Korea | 16 Participants | 69 Participants | 16 Participants | 21 Participants | 16 Participants |
| Region of Enrollment Spain | 16 Participants | 30 Participants | 0 Participants | 0 Participants | 14 Participants |
| Region of Enrollment Taiwan | 7 Participants | 33 Participants | 9 Participants | 9 Participants | 8 Participants |
| Region of Enrollment United States | 95 Participants | 187 Participants | 0 Participants | 0 Participants | 92 Participants |
| Sex: Female, Male Female | 162 Participants | 388 Participants | 27 Participants | 47 Participants | 152 Participants |
| Sex: Female, Male Male | 175 Participants | 449 Participants | 55 Participants | 35 Participants | 184 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 750 | 1 / 337 | 2 / 336 | 0 / 183 | 0 / 82 | 0 / 82 |
| other Total, other adverse events | 44 / 750 | 60 / 337 | 79 / 336 | 12 / 183 | 8 / 82 | 5 / 82 |
| serious Total, serious adverse events | 13 / 750 | 26 / 337 | 26 / 336 | 3 / 183 | 4 / 82 | 2 / 82 |
Outcome results
Primary
Change From Baseline in Hemoglobin A1c (HbA1c) Efficacy Estimand at Week 26
Change from baseline in HbA1c was performed using mixed model repeated measures (MMRM) including fixed class effects of treatment, strata (pooled country, type of basal insulin, and number of prandial doses at study entry), visit, and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline value. The efficacy estimand included participant data when baseline and at least one post-baseline measurement were available prior to permanent discontinuation of study drug.
Time frame: Baseline, Week 26
Population: All randomized participants with baseline and at least 1 post-baseline HbA1c data. As pre-specified in the analysis plan, outcome measures will not be reported for the Maximum Extended Enrollment (MEE) arms/groups but only for the main global study arms/groups.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Insulin Lispro (Humalog) | Change From Baseline in Hemoglobin A1c (HbA1c) Efficacy Estimand at Week 26 | -0.43 percentage of HbA1c | Standard Error 0.042 |
| LY900014 | Change From Baseline in Hemoglobin A1c (HbA1c) Efficacy Estimand at Week 26 | -0.38 percentage of HbA1c | Standard Error 0.042 |
95% CI: [-0.05, 0.16]
Secondary
1-hour Postprandial Glucose (PPG) Excursion During Mixed-Meal Tolerance Test (MMTT) Efficacy Estimand
1-hour PPG excursion during MMTT uses the analysis of covariance (ANCOVA) model with strata (pooled country, type of basal insulin, number of prandial doses at study entry, and HbA1c stratum) and treatment as fixed effects and baseline as a covariate. The efficacy estimand included participant data when baseline and at least one post-baseline measurement were available prior to permanent discontinuation of study drug.
Time frame: Week 26
Population: All randomized participants with baseline and at least one post-baseline 1-hour PPG excursion data. As pre-specified in the analysis plan, outcome measures will not be reported for the MEE arms/groups but only for the main global study arms/groups.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Insulin Lispro (Humalog) | 1-hour Postprandial Glucose (PPG) Excursion During Mixed-Meal Tolerance Test (MMTT) Efficacy Estimand | 74.9 milligrams per deciliter (mg/dL) | Standard Error 3.6 |
| LY900014 | 1-hour Postprandial Glucose (PPG) Excursion During Mixed-Meal Tolerance Test (MMTT) Efficacy Estimand | 63.1 milligrams per deciliter (mg/dL) | Standard Error 3.6 |
p-value: <0.00195% CI: [-18.1, -5.5]ANCOVA
Secondary
2-hour PPG Excursion During MMTT Efficacy Estimand
2-hour PPG excursion during MMTT uses the ANCOVA model with strata (pooled country, type of basal insulin, number of prandial doses at study entry, and HbA1c stratum) and treatment as fixed effects and baseline as a covariate. The efficacy estimand included participant data when baseline and at least one post-baseline measurement were available prior to permanent discontinuation of study drug.
Time frame: Week 26
Population: All randomized participants with baseline and at least one post-baseline 2-hour PPG excursion data. As pre-specified in the analysis plan, outcome measures will not be reported for the MEE arms/groups but only for the main global study arms/groups.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Insulin Lispro (Humalog) | 2-hour PPG Excursion During MMTT Efficacy Estimand | 97.8 mg/dL | Standard Error 4.5 |
| LY900014 | 2-hour PPG Excursion During MMTT Efficacy Estimand | 80.4 mg/dL | Standard Error 4.5 |
p-value: <0.00195% CI: [-25.3, -9.5]ANCOVA
Secondary
Change From Baseline in 10-Point Self-Monitoring Blood Glucose (SMBG) Values at Week 26
Change from baseline in 10-point SMBG values was analyzed using mixed model repeated measures (MMRM) including fixed class effects of treatment, strata (pooled country, type of basal insulin, HbA1c stratum and number of prandial doses at study entry), visit, and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline value. The efficacy estimand included participant data when baseline and at least one post-baseline measurement prior to permanent discontinuation of study drug.
Time frame: Baseline, Week 26
Population: All randomized participants with baseline and at least one post-baseline SMBG data. As pre-specified in the analysis plan, outcome measures will not be reported for the MEE arms/groups but only for the main global study arms/groups.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Lispro (Humalog) | Change From Baseline in 10-Point Self-Monitoring Blood Glucose (SMBG) Values at Week 26 | Morning Premeal | -0.8 mg/dL | Standard Error 2.72 |
| Insulin Lispro (Humalog) | Change From Baseline in 10-Point Self-Monitoring Blood Glucose (SMBG) Values at Week 26 | Morning 1-hour Postmeal | -2.0 mg/dL | Standard Error 3.44 |
| Insulin Lispro (Humalog) | Change From Baseline in 10-Point Self-Monitoring Blood Glucose (SMBG) Values at Week 26 | Morning 2-hour Postmeal | 0.6 mg/dL | Standard Error 3.38 |
| Insulin Lispro (Humalog) | Change From Baseline in 10-Point Self-Monitoring Blood Glucose (SMBG) Values at Week 26 | Midday Premeal | 2.4 mg/dL | Standard Error 2.83 |
| Insulin Lispro (Humalog) | Change From Baseline in 10-Point Self-Monitoring Blood Glucose (SMBG) Values at Week 26 | Midday 1-hour Postmeal | 3.0 mg/dL | Standard Error 3.48 |
| Insulin Lispro (Humalog) | Change From Baseline in 10-Point Self-Monitoring Blood Glucose (SMBG) Values at Week 26 | Midday 2-hour Postmeal | -2.2 mg/dL | Standard Error 3.28 |
| Insulin Lispro (Humalog) | Change From Baseline in 10-Point Self-Monitoring Blood Glucose (SMBG) Values at Week 26 | Evening Premeal | 7.0 mg/dL | Standard Error 3.38 |
| Insulin Lispro (Humalog) | Change From Baseline in 10-Point Self-Monitoring Blood Glucose (SMBG) Values at Week 26 | Evening 1-hour Postmeal | -2.1 mg/dL | Standard Error 3.24 |
| Insulin Lispro (Humalog) | Change From Baseline in 10-Point Self-Monitoring Blood Glucose (SMBG) Values at Week 26 | Evening 2-hour Postmeal | 0.2 mg/dL | Standard Error 3.68 |
| Insulin Lispro (Humalog) | Change From Baseline in 10-Point Self-Monitoring Blood Glucose (SMBG) Values at Week 26 | Bedtime | -3.4 mg/dL | Standard Error 4 |
| LY900014 | Change From Baseline in 10-Point Self-Monitoring Blood Glucose (SMBG) Values at Week 26 | Evening 1-hour Postmeal | -3.0 mg/dL | Standard Error 3.27 |
| LY900014 | Change From Baseline in 10-Point Self-Monitoring Blood Glucose (SMBG) Values at Week 26 | Morning Premeal | 1.5 mg/dL | Standard Error 2.74 |
| LY900014 | Change From Baseline in 10-Point Self-Monitoring Blood Glucose (SMBG) Values at Week 26 | Midday 2-hour Postmeal | -6.5 mg/dL | Standard Error 3.27 |
| LY900014 | Change From Baseline in 10-Point Self-Monitoring Blood Glucose (SMBG) Values at Week 26 | Morning 1-hour Postmeal | -14.1 mg/dL | Standard Error 3.44 |
| LY900014 | Change From Baseline in 10-Point Self-Monitoring Blood Glucose (SMBG) Values at Week 26 | Bedtime | -2.2 mg/dL | Standard Error 4.02 |
| LY900014 | Change From Baseline in 10-Point Self-Monitoring Blood Glucose (SMBG) Values at Week 26 | Morning 2-hour Postmeal | -14.9 mg/dL | Standard Error 3.38 |
| LY900014 | Change From Baseline in 10-Point Self-Monitoring Blood Glucose (SMBG) Values at Week 26 | Evening Premeal | 10.1 mg/dL | Standard Error 3.38 |
| LY900014 | Change From Baseline in 10-Point Self-Monitoring Blood Glucose (SMBG) Values at Week 26 | Midday Premeal | 4.1 mg/dL | Standard Error 2.84 |
| LY900014 | Change From Baseline in 10-Point Self-Monitoring Blood Glucose (SMBG) Values at Week 26 | Evening 2-hour Postmeal | -2.1 mg/dL | Standard Error 3.73 |
| LY900014 | Change From Baseline in 10-Point Self-Monitoring Blood Glucose (SMBG) Values at Week 26 | Midday 1-hour Postmeal | -2.0 mg/dL | Standard Error 3.47 |
Secondary
Change From Baseline in 1,5-Anhydroglucitol (1,5-AG) at Week 26
Change from baseline in 1,5-AG was analyzed using mixed model repeated measures (MMRM) including fixed class effects of treatment, strata (pooled country, type of basal insulin, HbA1c stratum and number of prandial doses at study entry), visit, and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline value. The analysis included data collected prior to permanent discontinuation of study drug.
Time frame: Baseline, Week 26
Population: All randomized participants with baseline and at least one post-baseline 1,5-AG data. As pre-specified in the analysis plan, outcome measures will not be reported for the MEE arms/groups but only for the main global study arms/groups.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Insulin Lispro (Humalog) | Change From Baseline in 1,5-Anhydroglucitol (1,5-AG) at Week 26 | 2.15 milligram per liter (mg/L) | Standard Error 0.234 |
| LY900014 | Change From Baseline in 1,5-Anhydroglucitol (1,5-AG) at Week 26 | 1.99 milligram per liter (mg/L) | Standard Error 0.235 |
Secondary
Change From Baseline in Insulin Dose at Week 26
Change from baseline in insulin dose was analyzed using mixed model repeated measures (MMRM) including fixed class effects of treatment, strata (pooled country, type of basal insulin, HbA1c stratum and number of prandial doses at study entry), visit, and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline value. The analysis included data prior to permanent discontinuation of study drug.
Time frame: Baseline, Week 26
Population: All randomized participants with baseline and at least one post-baseline basal insulin dose data. As pre-specified in the analysis plan, outcome measures will not be reported for the MEE arms/groups but only for the main global study arms/groups.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Lispro (Humalog) | Change From Baseline in Insulin Dose at Week 26 | Basal Insulin Dose | 4.2 Units (U) | Standard Error 0.82 |
| Insulin Lispro (Humalog) | Change From Baseline in Insulin Dose at Week 26 | Prandial Insulin Dose | 8.3 Units (U) | Standard Error 1.41 |
| Insulin Lispro (Humalog) | Change From Baseline in Insulin Dose at Week 26 | Total Daily Insulin Dose | 12.1 Units (U) | Standard Error 1.93 |
| LY900014 | Change From Baseline in Insulin Dose at Week 26 | Basal Insulin Dose | 4.6 Units (U) | Standard Error 0.81 |
| LY900014 | Change From Baseline in Insulin Dose at Week 26 | Prandial Insulin Dose | 12.0 Units (U) | Standard Error 1.41 |
| LY900014 | Change From Baseline in Insulin Dose at Week 26 | Total Daily Insulin Dose | 17.3 Units (U) | Standard Error 1.92 |
Secondary
Change From Baseline in Insulin Treatment Satisfaction Questionnaire (ITSQ) Regimen Inconvenience Domain Score at Week 26
ITSQ is a validated instrument containing 22 items that assess treatment satisfaction for participants with diabetes and on insulin. The questionnaire measures satisfaction from the following 5 domains: Inconvenience of Regimen, Lifestyle Flexibility, Glycemic Control, Hypoglycemic Control, and Insulin Delivery Device. Data presented are the transformed overall score on a scale of 0-100, where higher scores indicate better treatment satisfaction. Change from baseline in ITSQ regimen inconvenience domain score was calculated using the ANCOVA model with strata (pooled country, type of basal insulin, number of prandial doses at study entry, and HbA1c stratum), and treatment as fixed effects and baseline as covariate. The analysis included data prior to permanent discontinuation of study drug.
Time frame: Baseline, Week 26
Population: All randomized participants with baseline and post-baseline data. Missing endpoints were imputed by applying the Last Observation Carried Forward (LOCF) method to post-baseline data. As pre-specified in the analysis plan, outcome measures will not be reported for the MEE arms/groups but only for the main global study arms/groups.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Insulin Lispro (Humalog) | Change From Baseline in Insulin Treatment Satisfaction Questionnaire (ITSQ) Regimen Inconvenience Domain Score at Week 26 | -0.9 units on a scale | Standard Error 1.36 |
| LY900014 | Change From Baseline in Insulin Treatment Satisfaction Questionnaire (ITSQ) Regimen Inconvenience Domain Score at Week 26 | -2.4 units on a scale | Standard Error 1.37 |
Secondary
Change From Baseline in ITSQ Lifestyle Flexibility Domain Score at Week 26
ITSQ is a validated instrument containing 22 items that assess treatment satisfaction for participants with diabetes and on insulin. The questionnaire measures satisfaction from the following 5 domains: Inconvenience of Regimen, Lifestyle Flexibility, Glycemic Control, Hypoglycemic Control, and Insulin Delivery Device. Data presented are the transformed overall score on a scale of 0-100, where higher scores indicate better treatment satisfaction. Change from baseline in ITSQ lifestyle flexibility domain score was calculated using the ANCOVA model with strata (pooled country, type of basal insulin, number of prandial doses at study entry, and HbA1c stratum), and treatment as fixed effects and baseline as covariate. The analysis included data prior to permanent discontinuation of study drug.
Time frame: Baseline, Week 26
Population: All randomized participants with baseline and post-baseline data. Missing endpoints were imputed by applying the LOCF method to the post-baseline data. As pre-specified in the analysis plan, outcome measures will not be reported for the MEE arms/groups but only for the main global study arms/groups.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Insulin Lispro (Humalog) | Change From Baseline in ITSQ Lifestyle Flexibility Domain Score at Week 26 | 1.4 units on a scale | Standard Error 1.6 |
| LY900014 | Change From Baseline in ITSQ Lifestyle Flexibility Domain Score at Week 26 | 0.2 units on a scale | Standard Error 1.6 |
Secondary
Number of Participants With HbA1c <7%
Number of participants with HbA1c \<7% at Week 26.
Time frame: Week 26
Population: All participants with baseline and one post-baseline observation while on study drug. As pre-specified in the analysis plan, outcome measures will not be reported for the MEE arms/groups but only for the main global study arms/groups.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Insulin Lispro (Humalog) | Number of Participants With HbA1c <7% | 168 Participants |
| LY900014 | Number of Participants With HbA1c <7% | 184 Participants |
Secondary
Rate of Documented Symptomatic Hypoglycemia
Documented symptomatic hypoglycemia is an event during which typical symptoms of hypoglycemia are accompanied by blood glucose (BG) of \<54 mg/dL \[3.0 millimole per liter (mmol/L)\]. The rate of documented symptomatic hypoglycemia was estimated by negative binomial model: number of episodes = treatment with log (treatment exposure in days/365.25) as an offset variable.
Time frame: Baseline through Week 26
Population: All randomized participants with evaluable hypoglycemic data. As pre-specified in the analysis plan, outcome measures will not be reported for the MEE arms/groups but only for the main global study arms/groups.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Insulin Lispro (Humalog) | Rate of Documented Symptomatic Hypoglycemia | 1.34 Events per participant per 30 days/year | Standard Error 0.164 |
| LY900014 | Rate of Documented Symptomatic Hypoglycemia | 2.21 Events per participant per 30 days/year | Standard Error 0.318 |
Secondary
Rate of Severe Hypoglycemia
Rate of severe hypoglycemia events per 100 years during a defined period was calculated by total number of severe hypoglycemia episodes within the period divided by the cumulative days on treatment from all participants within a treatment group \*36525. Severe hypoglycemia is defined as an event requiring assistance of another person to administer carbohydrate, glucagon, or other resuscitative actions. During these episodes, the participant has an altered mental status and cannot assist in his or her own care, or may be semiconscious or unconscious, or experience com with or without seizures, and may require parenteral therapy.
Time frame: Baseline through Week 26
Population: All randomized participants with evaluable hypoglycemic data. As pre-specified in the analysis plan, outcome measures will not be reported for the MEE arms/groups but only for the main global study arms/groups.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Insulin Lispro (Humalog) | Rate of Severe Hypoglycemia | 4.19 Events per 100 participant years |
| LY900014 | Rate of Severe Hypoglycemia | 2.44 Events per 100 participant years |