Type 2 Diabetes Mellitus
Conditions
Brief summary
The purpose of this study is to determine the efficacy and safety of insulin Lispro Mix25 (LM25) compared to insulin Lispro Mix50 (LM50) as an insulin starter in participants with Type 2 diabetes mellitus (T2DM).
Interventions
DRUGInsulin Lispro Mix25
Administered SC
DRUGInsulin Lispro Mix50
Administered SC
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have a diagnosis of Type 2 Diabetes Mellitus (T2DM) for at least 6 months * Have been taking sulfonylureas, biguanide, thiazolidinedione, alpha-glucosidase inhibitor, glinide, or dipeptidyl peptidase IV inhibitor, or any combination of these * Have a qualifying hemoglobin A1c (HbA1C) value ≥7.0% and ≤11.0% at screening * Have a body mass index (BMI) ≥18.5 and \<35.0 kilogram per square meter (kg/m²) * Have given written informed consent to participate in the study in accordance with local regulations and the ethical review board (ERB) governing the study site
Exclusion criteria
* Have a diagnosis of type 1 diabetes * Have had more than 1 episode of severe hypoglycemia within the 6 months before screening * Have any of the following cardiovascular conditions within 3 months prior to screening: acute myocardial infarction, New York Heart Association (NYHA) class III or class IV heart failure, or cerebrovascular accident (stroke) * Have obvious clinical signs or symptoms of liver disease, acute or chronic hepatitis, or alanine aminotransferase levels ≥3.0 times the upper limit of the reference range at screening, as determined by the central laboratory * Have an estimated creatinine clearance (CrCl), Cockcroft-Gault formula \<30 milliliter per minute (mL/min), as determined by the central laboratory at screening * Have evidence of a significant, active, uncontrolled endocrine or autoimmune abnormality, as judged by the investigator * Have an active or untreated malignancy or have been in remission from a clinically significant malignancy for \<5 years * Have any other condition (such as, known drug or alcohol abuse or a psychiatric disorder) that may prevent the participants from following and completing the protocol * Are currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an investigational product or non-approved use of a drug or device, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Hemoglobin A1c (HbA1c) at Week 26 | Baseline, Week 26 | HbA1c is the glycosylated fraction of hemoglobin A which provides an estimate of a participant's blood sugar control over a 6- to 12-week period. Least Squares (LS) means were calculated by Mixed Models Repeated Measurements (MMRM) analysis using change from baseline in HbA1c at all post baseline measurement as dependent variables, treatment, blood glucose (BG) excursion, country, visit and treatment-by-visit interaction as fixed effects, baseline HbA1c value as a covariate and participants as a random effect. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Fasting Blood Glucose (FBG) at Week 26 | Baseline, Week 26 | LS means were calculated by MMRM analysis using change from baseline in FBG variables at all post baseline measurement as dependent variables, treatment, country, BG excursion, visit and treatment-by-visit interaction as fixed effects, baseline self-monitoring blood glucose (SMBG) variable value as a covariate and participants as a random effect. |
| Change From Baseline in Body Weight at Week 26 | Baseline, Week 26 | LS means were calculated by MMRM analysis using change from baseline in weight variables at all post baseline measurement as dependent variables, treatment, country, BG excursion, visit and treatment-by-visit interaction as fixed effects, baseline SMBG variable value as a covariate and participants as a random effect. |
| Percentage of Participants Achieving HbA1c of <7.0% or ≤6.5% Baseline Through Week 26 | Baseline through Week 26 | HbA1c is the glycosylated fraction of hemoglobin A which provides an estimate of a participant's blood sugar control over a 6- to 12-week period. The percentage of participants with HbA1c \<7.0% or HbA1c ≤6.5% is calculated as the number of participants with an HbA1c level of the cut-off value (\<7.0% or ≤6.5%) divided by the number of participants treated, then multiplied by 100. |
| Insulin Dose at Week 26 | Week 26 | Insulin dose is the total daily dose including basal and prandial doses. |
| Change From Baseline in 1,5-Anhydroglucitol (1,5-AG) at Week 26 | Baseline, Week 26 | LS means were calculated by MMRM analysis using change from baseline in 1.5-AG variables at all post baseline measurement as dependent variables, treatment, country, BG excursion, visit and treatment-by-visit interaction as fixed effects, baseline SMBG variable value as a covariate and participants as a random effect. |
| Number of Hypoglycemic Events Baseline Through Week 26 (Incidence) | Baseline through Week 26 | A hypoglycemic event is defined as any time a participant feels that he/she is experiencing a sign or symptom that is associated with hypoglycemia, or has a BG concentration of ≤ 70milligrams/deciliter \[mg/dL (3.9 mmol/L)\], even if it was not associated with signs, symptoms, or treatment consistent with current guidelines \[American Diabetes Association (ADA) 2005\]. |
Countries
China, Japan, South Korea, Turkey (Türkiye)
Participant flow
Pre-assignment details
This study consisted of a 26-week treatment period (12-week, weekly-intensive, dose-adjustment period and 14-week maintenance period).
Participants by arm
| Arm | Count |
|---|---|
| Insulin Lispro Mix25 Insulin Lispro Mix25 administered SC using prefilled pen twice daily for 26 weeks. | 207 |
| Insulin Lispro Mix50 Insulin Lispro Mix50 administered SC using prefilled pen twice daily for 26 weeks. | 196 |
| Total | 403 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 2 |
| Overall Study | Lack of Efficacy | 0 | 1 |
| Overall Study | Lost to Follow-up | 2 | 0 |
| Overall Study | Non-Compliance with study drug | 1 | 4 |
| Overall Study | Physician Decision | 3 | 5 |
| Overall Study | Protocol Violation | 0 | 4 |
| Overall Study | Sponsor Decision | 2 | 0 |
| Overall Study | Withdrawal by Subject | 5 | 3 |
Baseline characteristics
| Characteristic | Insulin Lispro Mix25 | Insulin Lispro Mix50 | Total |
|---|---|---|---|
| Age, Continuous | 55.74 years STANDARD_DEVIATION 10.026 | 57.34 years STANDARD_DEVIATION 9.664 | 56.52 years STANDARD_DEVIATION 9.871 |
| Duration of Type-2 Diabetes Mellitus (T2DM) | 9.74 years STANDARD_DEVIATION 6.169 | 9.15 years STANDARD_DEVIATION 6.336 | 9.45 years STANDARD_DEVIATION 6.25 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 192 Participants | 182 Participants | 374 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 15 Participants | 14 Participants | 29 Participants |
| Region of Enrollment China | 80 participants | 76 participants | 156 participants |
| Region of Enrollment Japan | 88 participants | 84 participants | 172 participants |
| Region of Enrollment Korea, Republic of | 24 participants | 22 participants | 46 participants |
| Region of Enrollment Turkey | 15 participants | 14 participants | 29 participants |
| Sex: Female, Male Female | 76 Participants | 77 Participants | 153 Participants |
| Sex: Female, Male Male | 131 Participants | 119 Participants | 250 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 87 / 207 | 84 / 196 |
| serious Total, serious adverse events | 8 / 207 | 7 / 196 |
Outcome results
Primary
Change From Baseline in Hemoglobin A1c (HbA1c) at Week 26
HbA1c is the glycosylated fraction of hemoglobin A which provides an estimate of a participant's blood sugar control over a 6- to 12-week period. Least Squares (LS) means were calculated by Mixed Models Repeated Measurements (MMRM) analysis using change from baseline in HbA1c at all post baseline measurement as dependent variables, treatment, blood glucose (BG) excursion, country, visit and treatment-by-visit interaction as fixed effects, baseline HbA1c value as a covariate and participants as a random effect.
Time frame: Baseline, Week 26
Population: All randomized participants who received at least 1 dose of study drug and analyzed according to the assigned treatment regardless of study drug dose the participant received and had baseline and Week 26 HbA1c measurements.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Insulin Lispro Mix25 | Change From Baseline in Hemoglobin A1c (HbA1c) at Week 26 | -1.52 percentage of glycosylated hemoglobin |
| Insulin Lispro Mix50 | Change From Baseline in Hemoglobin A1c (HbA1c) at Week 26 | -1.69 percentage of glycosylated hemoglobin |
95% CI: [-0.01, 0.35]
Secondary
Change From Baseline in 1,5-Anhydroglucitol (1,5-AG) at Week 26
LS means were calculated by MMRM analysis using change from baseline in 1.5-AG variables at all post baseline measurement as dependent variables, treatment, country, BG excursion, visit and treatment-by-visit interaction as fixed effects, baseline SMBG variable value as a covariate and participants as a random effect.
Time frame: Baseline, Week 26
Population: All randomized participants who received at least 1 dose of study drug and analyzed according to the assigned treatment regardless of study drug dose the participant received and had baseline and Week 26 1,5-AG measurements.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Insulin Lispro Mix25 | Change From Baseline in 1,5-Anhydroglucitol (1,5-AG) at Week 26 | 4.24 micrograms/milliliter (µg/mL) |
| Insulin Lispro Mix50 | Change From Baseline in 1,5-Anhydroglucitol (1,5-AG) at Week 26 | 5.62 micrograms/milliliter (µg/mL) |
Secondary
Change From Baseline in Body Weight at Week 26
LS means were calculated by MMRM analysis using change from baseline in weight variables at all post baseline measurement as dependent variables, treatment, country, BG excursion, visit and treatment-by-visit interaction as fixed effects, baseline SMBG variable value as a covariate and participants as a random effect.
Time frame: Baseline, Week 26
Population: All randomized participants who received at least 1 dose of study drug and had baseline and Week 26 body weight measurements.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Insulin Lispro Mix25 | Change From Baseline in Body Weight at Week 26 | 2.31 kilogram (kg) |
| Insulin Lispro Mix50 | Change From Baseline in Body Weight at Week 26 | 2.32 kilogram (kg) |
Secondary
Change From Baseline in Fasting Blood Glucose (FBG) at Week 26
LS means were calculated by MMRM analysis using change from baseline in FBG variables at all post baseline measurement as dependent variables, treatment, country, BG excursion, visit and treatment-by-visit interaction as fixed effects, baseline self-monitoring blood glucose (SMBG) variable value as a covariate and participants as a random effect.
Time frame: Baseline, Week 26
Population: All randomized participants who received at least 1 dose of study drug and analyzed according to the assigned treatment regardless of study drug dose the participant received and had baseline and Week 26 FBG measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Insulin Lispro Mix25 | Change From Baseline in Fasting Blood Glucose (FBG) at Week 26 | -2.37 millimoles per liter (mmol/L) |
| Insulin Lispro Mix50 | Change From Baseline in Fasting Blood Glucose (FBG) at Week 26 | -1.99 millimoles per liter (mmol/L) |
Secondary
Insulin Dose at Week 26
Insulin dose is the total daily dose including basal and prandial doses.
Time frame: Week 26
Population: All randomized participants who received at least 1 dose of study drug and analyzed according to the assigned treatment regardless of study drug dose the participant received and had Week 26 insulin dose measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin Lispro Mix25 | Insulin Dose at Week 26 | 40.02 units of insulin per day (IU/day) | Standard Deviation 17.771 |
| Insulin Lispro Mix50 | Insulin Dose at Week 26 | 39.32 units of insulin per day (IU/day) | Standard Deviation 17.991 |
Secondary
Number of Hypoglycemic Events Baseline Through Week 26 (Incidence)
A hypoglycemic event is defined as any time a participant feels that he/she is experiencing a sign or symptom that is associated with hypoglycemia, or has a BG concentration of ≤ 70milligrams/deciliter \[mg/dL (3.9 mmol/L)\], even if it was not associated with signs, symptoms, or treatment consistent with current guidelines \[American Diabetes Association (ADA) 2005\].
Time frame: Baseline through Week 26
Population: All randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Insulin Lispro Mix25 | Number of Hypoglycemic Events Baseline Through Week 26 (Incidence) | All Hypoglycemic Events | 568 events |
| Insulin Lispro Mix25 | Number of Hypoglycemic Events Baseline Through Week 26 (Incidence) | Severe Hypoglycemic Events | 0 events |
| Insulin Lispro Mix50 | Number of Hypoglycemic Events Baseline Through Week 26 (Incidence) | All Hypoglycemic Events | 583 events |
| Insulin Lispro Mix50 | Number of Hypoglycemic Events Baseline Through Week 26 (Incidence) | Severe Hypoglycemic Events | 1 events |
Secondary
Percentage of Participants Achieving HbA1c of <7.0% or ≤6.5% Baseline Through Week 26
HbA1c is the glycosylated fraction of hemoglobin A which provides an estimate of a participant's blood sugar control over a 6- to 12-week period. The percentage of participants with HbA1c \<7.0% or HbA1c ≤6.5% is calculated as the number of participants with an HbA1c level of the cut-off value (\<7.0% or ≤6.5%) divided by the number of participants treated, then multiplied by 100.
Time frame: Baseline through Week 26
Population: All randomized participants who received at least 1 dose of study drug and analyzed according to the assigned treatment regardless of study drug dose the participant received and had baseline and at least 1 post-baseline HbA1c measurement.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Insulin Lispro Mix25 | Percentage of Participants Achieving HbA1c of <7.0% or ≤6.5% Baseline Through Week 26 | <7.0% | 45.9 percentage of participants |
| Insulin Lispro Mix25 | Percentage of Participants Achieving HbA1c of <7.0% or ≤6.5% Baseline Through Week 26 | ≤6.5% | 26.1 percentage of participants |
| Insulin Lispro Mix50 | Percentage of Participants Achieving HbA1c of <7.0% or ≤6.5% Baseline Through Week 26 | <7.0% | 59.7 percentage of participants |
| Insulin Lispro Mix50 | Percentage of Participants Achieving HbA1c of <7.0% or ≤6.5% Baseline Through Week 26 | ≤6.5% | 42.3 percentage of participants |