Type 2 Diabetes Mellitus
Conditions
Brief summary
The purpose of this study is to compare insulin peglispro (LY2605541) to insulin glargine in Asian insulin naïve participants who have been treated with oral anti hyperglycemia medications. Participants will receive 26 weeks of treatment.
Interventions
Administered SC using a prefilled pen.
DRUGInsulin Glargine
Administered SC using a prefilled pen
DRUGOral Antihyperglycemic Medications (OAMs)
Administered orally
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have Type 2 Diabetes Mellitus (T2DM) for at least 1 year not treated with insulin * Have been receiving at least two oral antihyperglycemic medications (OAMs) for at least 3 months prior to screening * Have Hemoglobin A1c (HbA1c) of 7.0% to 11.0%, inclusive, according to central laboratory at screening * Body mass index (BMI) ≤35.0 kilogram per square meter (kg/m\^2) * Inject insulin with a pre-filled insulin pen and perform Self-Monitored Blood Glucose (SMBG) * Record keeping as required by this protocol * Women of childbearing potential are not breastfeeding, have a negative pregnancy test at screening, do not plan to become pregnant during the study, have practiced reliable birth control during the study and 2 weeks following the last dose of investigational product
Exclusion criteria
* Have used insulin therapy (outside of pregnancy) anytime in the past 2 years, except for short term treatment of acute conditions * Have been treated with rosiglitazone, pramlintide, glucagon-like peptide-1 (GLP-1) receptor agonist within 3 months prior to screening * Are using or have used any of the following lipid-lowering medications: niacin preparations as a lipid-lowering medication and/or bile acid sequestrants within 90 days prior to screening * Local OAM restrictions: have any restrictions for cardiac, renal, and hepatic diseases in the local product regulations * Are taking, or have taken within 3 months before screening, prescription or over-the-counter medications to promote weight loss * Have had any episodes of severe hypoglycemia, diabetic ketoacidosis, or hyperosmolar state/coma within 6 months prior to screening * Have had 1 or more episodes of ketoacidosis or hyperosmolar state/coma in the past 6 months * Have cardiac disease with functional status that is New York Heart Association Class III or IV * Have a history of renal transplantation, or are currently receiving renal dialysis or have serum creatinine ≥2.0 milligram per deciliter (mg/dL) (177 micromole per liter \[μmol/L\]). Participants taking metformin should not exceed the creatinine level specified in the local label * Have obvious clinical signs or symptoms of liver disease (excluding non-alcoholic fatty liver disease \[NAFLD\]), acute or any chronic hepatitis, non alcoholic steatohepatitis (NASH), or elevated liver enzyme measurements * Have had a blood transfusion or severe blood loss within 3 months prior to screening or have known hemoglobinopathy, hemolytic anemia or sickle cell anemia, or any other traits of hemoglobin abnormalities known to interfere with the measurement of HbA1c * Have active or untreated cancer, have been in remission from clinically significant cancer(other than basal cell or squamous cell skin cancer) for less than 5 years, or are at increased risk for developing cancer or a recurrence of cancer in the opinion of the investigator * Have known hypersensitivity or allergy to any of LY2605541 and insulin glargine or their excipients * Have pre proliferative and proliferative retinopathy, maculopathy requiring treatment or not clinically stable in the last 6 months, or participants with active changes in subjective eye symptoms as determined by the investigator if an eye exam has not been performed in the last 6 months * Are receiving chronic (lasting longer than 14 consecutive days) systemic glucocorticoid therapy (excluding topical, intranasal, intraocular, and inhaled preparations) or have received such therapy within the 8 weeks immediately preceding screening * Have fasting triglycerides greater than 400 mg/dL (4.5 mmol/L) at screening as determined by the central laboratory * Have an irregular sleep/wake cycle (for example, participants who sleep during the day and work during the night) in the investigator's opinion
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 26 in Hemoglobin A1c (HbA1c) | Baseline, Week 26 | Hemoglobin A1c (HbA1c) is a test that measures a participant's average blood glucose level over the past 2 to 3 months. Least Squares (LS) means were calculated using a mixed model repeated measures (MMRM) analysis adjusting for treatment, stratification factors (region, sulfonylureas/meglitinide use, baseline Low-Density Lipoprotein \[LDL-C\], visit, treatment-by-visit interaction, and baseline HbA1c as fixed effects and participants as the random effect. P-value is from MMRM with terms for treatment, visit, treatment-by-visit interaction, stratification, and baseline HbA1C. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Fasting Serum Glucose (FSG) | Weeks 0 and 26 | LS means were calculated using MMRM analysis adjusting for baseline, treatment, stratification factor (region, HbA1c, LDL-C, and sulfonylurea \[SU\]/meglitinide use), visit, and treatment-by-visit interaction. |
| Fasting Blood Glucose (FBG) | Weeks 0 and 26 | LS Means were calculated using MMRM analysis adjusting for baseline, treatment, stratification factor (region, HbA1c, LDL-C, and SU/meglitinide use), visit and treatment-by-visit interaction. |
| Change From Baseline to Week 26 in Body Weight | Baseline, Week 26 | LS Means were calculated using MMRM analysis adjusting for baseline, treatment, stratification factor (region, HbA1c, LDL-C, and SU/meglitinide use), visit and treatment-by-visit interaction. |
| 9-Point Self-Monitored Blood Glucose (SMBG) | Week 0 and Week 26 | LS means were calculated using MMRM analysis adjusting for baseline, treatment, stratification factor (region, HbA1c, LDL-C, and SU/meglitinide use), visit and treatment-by-visit interaction. The 9-point SMBG are measured at: Pre-morning meal, 2 hours(hr) post morning meal, pre-midday meal, 2 hr post midday meal, pre-evening meal, 2 hr post pre-evening meal, bedtime, 0300 hr, and pre-morning meal next day, and should be performed on 2 non-consecutive days. |
| Percentage of Participants With HbA1c ≤6.5% | Week 26 | Percentage of participants with HbA1c ≤6.5% at Week 26 were made using a logistic regression model for endpoint used last observation carried forward (LOCF) method including treatment, baseline HbA1c value. |
| Insulin Dose Per Kilogram (kg) of Body Weight | Week 26 | LS means were calculated using MMRM analysis adjusting for baseline, treatment, stratification factor (region, HbA1c, LDL-C, and SU/meglitinide), visit, and treatment-by-visit interaction. |
| Percentage of Participants Achieving Steady-State of Basal Insulin Dose at 26 Weeks (Time to Steady State for Basal Insulin [Stable Maximum Dose]) | Week 26 | — |
| Concentration of Triglycerides, Total Cholesterol, Low-Density Lipoprotein (LDL-C), and High-Density Lipoprotein Cholesterol (HDL-C) at Week 26 | Week 26 | LS means were calculated using MMRM analysis adjusting for baseline, treatment, stratification factor (region, HbA1c, LDL-C, and SU/meglitinide use), visit, and treatment-by-visit interaction. |
| 30-Day Adjusted Rate of Total and Nocturnal Hypoglycemic Events | Baseline to Week 26 | Hypoglycemia Events (HE) occurs when blood glucose level ≤ 70 milligram per deciliter (mg/dL) (\<3.9 micromoles per liter \[mmol/L\]). Nocturnal HE includes any total HE that occurred between bedtime and waking. Group mean rates of nocturnal hypoglycemia (per 30 days) are presented and were calculated from negative binomial regression models with treatment, baseline sulfonylurea/meglitinide use, baseline total hypoglycemia event rate, log (exposure/30 days) as the offset in the model. Group Mean is estimated by taking the inverse link function on individual participant covariates first and then averages over all participants. |
| Percentage of Participants With Total and Nocturnal Hypoglycemic Events (HE) | Baseline to Week 26 | Percentage of participants with hypoglycemic events (total or nocturnal) to Week 26 based on BG Threshold 70mg/dL. |
| Change From Baseline of European Quality of Life-5 Dimensions - 3 Levels (EuroQoL-5D-3L ) Index Score and Visual Analog Scale (VAS) Health State Score at Week 26 | Baseline, Week 26 | The EuroQoL-5D-3L questionnaire is a generic, multidimensional, health-related, quality-of-life instrument. The profile allows participants to rate their health state in 5 health domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression using a 3-level scale of 1 to 3 (no problem, some problems, and extreme problems). These combinations of attributes are converted into a weighted health-state Index Score according to the United States population-based algorithm. Scores ranged from -0.11 to 1.0 where a score of 1.0 indicates perfect health. Overall health state score was self-reported using a VAS marked on a scale of 0 to 100 (0 indicates worst imaginable health state and 100 indicates best imaginable health state. LS means were calculated using analysis of covariance (ANCOVA) for actual measures and changes from baseline at endpoint using LOCF method: adjusting for treatment, stratification factors (region, HbA1c and SU/meglitin. |
| Insulin Treatment Satisfaction Questionnaire (ITSQ) Score | Week 4 and 26 | The Insulin Treatment Satisfaction Questionnaire is a validated instrument containing 22 items that assessed treatment satisfaction for participants with diabetes 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 score on a scale of 0-100, where a higher score indicate better treatment satisfaction. LS means was achieved using a MMRM model for post-baseline measures with stratification factors (country, HbA1c, and SU/meglitinide use) treatment, visit, treatment-by-visit as fixed effects. ITSQ was assessed at Week 4 (baseline) and Week 26. |
| Change From Baseline to 26 Weeks in Adult Low Blood Sugar Survey (LBSS) Scores | Baseline, Week 26 | LBSS is a validated, participant-reported 33-item questionnaire with items rated on a 5-point Likert scale, where 0 = never and 5 - always. The LBSS measures behaviors to avoid hypoglycemia and its negative consequences (15 items) and worries about hypoglycemia and its negative consequences (18 items). Total score is the sum of all items (range 0 to 132). Higher total scores reflect greater fear of hypoglycemia. Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) with country, treatment and metformin use as fixed effects and baseline score as a covariate. LBSS was assessed during screening visit (baseline) and again at Week 26. |
| Intra-Participant Variability of the Fasting Blood Glucose (FBG) | Week 26 | Intra-participant variability of Fasting Blood Glucose (FBG), which was measured by Self Monitored Blood Glucose (SMBG), was assessed by the standard deviation of the FBG measurement at the Week 26 visit. LS means were calculated using a MMRM with baseline fasting blood glucose measurement, stratification factors (country, HbA1c, LDL-C \[\< 100 mg/dL and ≥ 100 mg/dL\], and SU/meglitinide use), treatment, visit, and treatment-by-visit interaction as fixed effects. |
| Change From Baseline to 12 Weeks in Hemoglobin A1c (HbA1c) | Baseline, Week 12 | Hemoglobin A1c (HbA1c) is a test that measures a participant's average blood glucose level over the past 2 to 3 months.LS means were calculated using a MMRM with baseline HbA1C measurement, stratification factors (country, HbA1c, LDL-C \[\< 100 mg/dL and ≥ 100 mg/dL\], and SU/meglitinide use), treatment, visit, and treatment-by-visit interaction as fixed effects. |
| Percent Hemoglobin A1c at Week 26 | Week 26 | HbA1c is a test that measures a participant's average blood glucose level over the past 2 to 3 months. LS means were calculated using a MMRM with baseline HbA1C measurement, stratification factors (country, HbA1c, LDL-C \[\< 100 mg/dL and ≥ 100 mg/dL\], and SU/meglitinide use), treatment, visit, and treatment-by-visit interaction as fixed effects. |
| Percentage of Participants With Detectable Anti-Insulin Peglispro Antibodies at Week 26 | Week 26 | For participants with detectable anti-insulin peglispro antibody level, the percentage of participants with positive cross-react with endogenous insulin was summarized. |
Countries
Japan, South Korea, Taiwan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Insulin Peglispro Insulin Peglispro administered SC once daily for 26 weeks. | 192 |
| Insulin Glargine Insulin Glargine administered SC once daily for 26 weeks. | 196 |
| Total | 388 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 3 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Protocol required discontinuation | 2 | 1 |
| Overall Study | Withdrawal by Subject | 5 | 5 |
Baseline characteristics
| Characteristic | Insulin Glargine | Total | Insulin Peglispro |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 43 Participants | 94 Participants | 51 Participants |
| Age, Categorical Between 18 and 65 years | 153 Participants | 294 Participants | 141 Participants |
| Baseline Hemoglobin A1c (HbA1c) | 8.48 percent of HbA1c STANDARD_DEVIATION 0.85 | 8.53 percent of HbA1c STANDARD_DEVIATION 0.97 | 8.59 percent of HbA1c STANDARD_DEVIATION 1.09 |
| Fasting Serum Glucose (FSG) | 166.64 milligram per deciliter (mg/dL) STANDARD_DEVIATION 36.81 | 165.88 milligram per deciliter (mg/dL) STANDARD_DEVIATION 39.03 | 165.11 milligram per deciliter (mg/dL) STANDARD_DEVIATION 41.25 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 196 Participants | 388 Participants | 192 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 | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Japan | 102 Participants | 205 Participants | 103 Participants |
| Region of Enrollment South Korea | 52 Participants | 101 Participants | 49 Participants |
| Region of Enrollment Taiwan | 42 Participants | 82 Participants | 40 Participants |
| Sex: Female, Male Female | 90 Participants | 171 Participants | 81 Participants |
| Sex: Female, Male Male | 106 Participants | 217 Participants | 111 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 61 / 192 | 42 / 196 |
| serious Total, serious adverse events | 9 / 192 | 5 / 196 |
Outcome results
Primary
Change From Baseline to Week 26 in Hemoglobin A1c (HbA1c)
Hemoglobin A1c (HbA1c) is a test that measures a participant's average blood glucose level over the past 2 to 3 months. Least Squares (LS) means were calculated using a mixed model repeated measures (MMRM) analysis adjusting for treatment, stratification factors (region, sulfonylureas/meglitinide use, baseline Low-Density Lipoprotein \[LDL-C\], visit, treatment-by-visit interaction, and baseline HbA1c as fixed effects and participants as the random effect. P-value is from MMRM with terms for treatment, visit, treatment-by-visit interaction, stratification, and baseline HbA1C.
Time frame: Baseline, Week 26
Population: All participants who were randomized and received at least 1 dose of study drug and had evaluable HbA1c data
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Insulin Peglispro | Change From Baseline to Week 26 in Hemoglobin A1c (HbA1c) | -1.61 percent of HbA1c | Standard Error 0.06 |
| Insulin Glargine | Change From Baseline to Week 26 in Hemoglobin A1c (HbA1c) | -1.36 percent of HbA1c | Standard Error 0.06 |
p-value: 0.00595% CI: [-0.41, -0.07]Mixed Models Analysis
Secondary
30-Day Adjusted Rate of Total and Nocturnal Hypoglycemic Events
Hypoglycemia Events (HE) occurs when blood glucose level ≤ 70 milligram per deciliter (mg/dL) (\<3.9 micromoles per liter \[mmol/L\]). Nocturnal HE includes any total HE that occurred between bedtime and waking. Group mean rates of nocturnal hypoglycemia (per 30 days) are presented and were calculated from negative binomial regression models with treatment, baseline sulfonylurea/meglitinide use, baseline total hypoglycemia event rate, log (exposure/30 days) as the offset in the model. Group Mean is estimated by taking the inverse link function on individual participant covariates first and then averages over all participants.
Time frame: Baseline to Week 26
Population: All participants who were randomized and received at least 1 dose of study drug and had evaluable HE data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Peglispro | 30-Day Adjusted Rate of Total and Nocturnal Hypoglycemic Events | Total HE | 1.28 Number of events per participant per 30d | Standard Error 0.23 |
| Insulin Peglispro | 30-Day Adjusted Rate of Total and Nocturnal Hypoglycemic Events | Nocturnal HE | 0.19 Number of events per participant per 30d | Standard Error 0.12 |
| Insulin Glargine | 30-Day Adjusted Rate of Total and Nocturnal Hypoglycemic Events | Total HE | 1.21 Number of events per participant per 30d | Standard Error 0.23 |
| Insulin Glargine | 30-Day Adjusted Rate of Total and Nocturnal Hypoglycemic Events | Nocturnal HE | 0.27 Number of events per participant per 30d | Standard Error 0.18 |
Secondary
9-Point Self-Monitored Blood Glucose (SMBG)
LS means were calculated using MMRM analysis adjusting for baseline, treatment, stratification factor (region, HbA1c, LDL-C, and SU/meglitinide use), visit and treatment-by-visit interaction. The 9-point SMBG are measured at: Pre-morning meal, 2 hours(hr) post morning meal, pre-midday meal, 2 hr post midday meal, pre-evening meal, 2 hr post pre-evening meal, bedtime, 0300 hr, and pre-morning meal next day, and should be performed on 2 non-consecutive days.
Time frame: Week 0 and Week 26
Population: All participants who were randomized and received at least 1 dose of study drug and had evaluable SMBG data.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Peglispro | 9-Point Self-Monitored Blood Glucose (SMBG) | Morning Pre-meal Wk0 | 160.19 mg/dL | Standard Error 2.65 |
| Insulin Peglispro | 9-Point Self-Monitored Blood Glucose (SMBG) | Morning Pre-meal Wk26 | 108.24 mg/dL | Standard Error 1.68 |
| Insulin Peglispro | 9-Point Self-Monitored Blood Glucose (SMBG) | Morning Post-meal Wk0 | 237.19 mg/dL | Standard Error 4.26 |
| Insulin Peglispro | 9-Point Self-Monitored Blood Glucose (SMBG) | Morning Post-meal Wk26 | 176.97 mg/dL | Standard Error 3.31 |
| Insulin Peglispro | 9-Point Self-Monitored Blood Glucose (SMBG) | Mid-day Pre-meal Wk0 | 169.24 mg/dL | Standard Error 3.8 |
| Insulin Peglispro | 9-Point Self-Monitored Blood Glucose (SMBG) | Mid-day Pre-meal Wk26 | 122.01 mg/dL | Standard Error 2.56 |
| Insulin Peglispro | 9-Point Self-Monitored Blood Glucose (SMBG) | Mid-day Post-meal Wk0 | 224.22 mg/dL | Standard Error 4.23 |
| Insulin Peglispro | 9-Point Self-Monitored Blood Glucose (SMBG) | Mid-day Post-meal Wk26 | 182.32 mg/dL | Standard Error 3.26 |
| Insulin Peglispro | 9-Point Self-Monitored Blood Glucose (SMBG) | Evening Pre-meal Wk0 | 176.49 mg/dL | Standard Error 3.8 |
| Insulin Peglispro | 9-Point Self-Monitored Blood Glucose (SMBG) | Evening Pre-meal Wk26 | 131.65 mg/dL | Standard Error 3.08 |
| Insulin Peglispro | 9-Point Self-Monitored Blood Glucose (SMBG) | Evening Post-meal Wk0 | 219.45 mg/dL | Standard Error 4.2 |
| Insulin Peglispro | 9-Point Self-Monitored Blood Glucose (SMBG) | Evening Post-meal Wk26 | 176.23 mg/dL | Standard Error 3.37 |
| Insulin Peglispro | 9-Point Self-Monitored Blood Glucose (SMBG) | Bed Time Wk0 | 198.64 mg/dL | Standard Error 3.9 |
| Insulin Peglispro | 9-Point Self-Monitored Blood Glucose (SMBG) | Bed Time Wk26 | 153.41 mg/dL | Standard Error 2.95 |
| Insulin Peglispro | 9-Point Self-Monitored Blood Glucose (SMBG) | 0300 Hours (Hrs) Wk0 | 158.82 mg/dL | Standard Error 3.23 |
| Insulin Peglispro | 9-Point Self-Monitored Blood Glucose (SMBG) | 0300 Hrs Wk26 | 115.18 mg/dL | Standard Error 2.34 |
| Insulin Peglispro | 9-Point Self-Monitored Blood Glucose (SMBG) | Pre-morning Meal Next Day Wk0 | 156.28 mg/dL | Standard Error 2.57 |
| Insulin Peglispro | 9-Point Self-Monitored Blood Glucose (SMBG) | Pre-morning Meal Next Day Wk26 | 108.42 mg/dL | Standard Error 1.73 |
| Insulin Glargine | 9-Point Self-Monitored Blood Glucose (SMBG) | Bed Time Wk26 | 161.44 mg/dL | Standard Error 2.87 |
| Insulin Glargine | 9-Point Self-Monitored Blood Glucose (SMBG) | Morning Pre-meal Wk0 | 162.83 mg/dL | Standard Error 2.62 |
| Insulin Glargine | 9-Point Self-Monitored Blood Glucose (SMBG) | Evening Pre-meal Wk26 | 135.55 mg/dL | Standard Error 2.99 |
| Insulin Glargine | 9-Point Self-Monitored Blood Glucose (SMBG) | Morning Pre-meal Wk26 | 108.71 mg/dL | Standard Error 1.65 |
| Insulin Glargine | 9-Point Self-Monitored Blood Glucose (SMBG) | Pre-morning Meal Next Day Wk26 | 105.18 mg/dL | Standard Error 1.71 |
| Insulin Glargine | 9-Point Self-Monitored Blood Glucose (SMBG) | Morning Post-meal Wk0 | 233.37 mg/dL | Standard Error 4.21 |
| Insulin Glargine | 9-Point Self-Monitored Blood Glucose (SMBG) | Evening Post-meal Wk0 | 219.54 mg/dL | Standard Error 4.16 |
| Insulin Glargine | 9-Point Self-Monitored Blood Glucose (SMBG) | Morning Post-meal Wk26 | 176.93 mg/dL | Standard Error 3.23 |
| Insulin Glargine | 9-Point Self-Monitored Blood Glucose (SMBG) | 0300 Hours (Hrs) Wk0 | 162.13 mg/dL | Standard Error 3.2 |
| Insulin Glargine | 9-Point Self-Monitored Blood Glucose (SMBG) | Mid-day Pre-meal Wk0 | 166.68 mg/dL | Standard Error 3.76 |
| Insulin Glargine | 9-Point Self-Monitored Blood Glucose (SMBG) | Evening Post-meal Wk26 | 182.80 mg/dL | Standard Error 3.26 |
| Insulin Glargine | 9-Point Self-Monitored Blood Glucose (SMBG) | Mid-day Pre-meal Wk26 | 122.85 mg/dL | Standard Error 2.5 |
| Insulin Glargine | 9-Point Self-Monitored Blood Glucose (SMBG) | Pre-morning Meal Next Day Wk0 | 159.96 mg/dL | Standard Error 2.55 |
| Insulin Glargine | 9-Point Self-Monitored Blood Glucose (SMBG) | Mid-day Post-meal Wk0 | 226.11 mg/dL | Standard Error 4.21 |
| Insulin Glargine | 9-Point Self-Monitored Blood Glucose (SMBG) | Bed Time Wk0 | 197.68 mg/dL | Standard Error 3.83 |
| Insulin Glargine | 9-Point Self-Monitored Blood Glucose (SMBG) | Mid-day Post-meal Wk26 | 183.88 mg/dL | Standard Error 3.18 |
| Insulin Glargine | 9-Point Self-Monitored Blood Glucose (SMBG) | 0300 Hrs Wk26 | 114.77 mg/dL | Standard Error 2.27 |
| Insulin Glargine | 9-Point Self-Monitored Blood Glucose (SMBG) | Evening Pre-meal Wk0 | 172.83 mg/dL | Standard Error 3.75 |
Secondary
Change From Baseline of European Quality of Life-5 Dimensions - 3 Levels (EuroQoL-5D-3L ) Index Score and Visual Analog Scale (VAS) Health State Score at Week 26
The EuroQoL-5D-3L questionnaire is a generic, multidimensional, health-related, quality-of-life instrument. The profile allows participants to rate their health state in 5 health domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression using a 3-level scale of 1 to 3 (no problem, some problems, and extreme problems). These combinations of attributes are converted into a weighted health-state Index Score according to the United States population-based algorithm. Scores ranged from -0.11 to 1.0 where a score of 1.0 indicates perfect health. Overall health state score was self-reported using a VAS marked on a scale of 0 to 100 (0 indicates worst imaginable health state and 100 indicates best imaginable health state. LS means were calculated using analysis of covariance (ANCOVA) for actual measures and changes from baseline at endpoint using LOCF method: adjusting for treatment, stratification factors (region, HbA1c and SU/meglitin.
Time frame: Baseline, Week 26
Population: All participants who were randomized and received at least 1 dose of study drug and had evaluable EQ-5D data. Missing endpoints were imputed with last observation carried forward (LOCF).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Peglispro | Change From Baseline of European Quality of Life-5 Dimensions - 3 Levels (EuroQoL-5D-3L ) Index Score and Visual Analog Scale (VAS) Health State Score at Week 26 | Change from Baseline to Endpoint EQ-5D-3L Score | 0.01 units on a scale | Standard Error 0.01 |
| Insulin Peglispro | Change From Baseline of European Quality of Life-5 Dimensions - 3 Levels (EuroQoL-5D-3L ) Index Score and Visual Analog Scale (VAS) Health State Score at Week 26 | Change from Baseline VAS Health State Score | 2.29 units on a scale | Standard Error 0.92 |
| Insulin Glargine | Change From Baseline of European Quality of Life-5 Dimensions - 3 Levels (EuroQoL-5D-3L ) Index Score and Visual Analog Scale (VAS) Health State Score at Week 26 | Change from Baseline to Endpoint EQ-5D-3L Score | 0.00 units on a scale | Standard Error 0.01 |
| Insulin Glargine | Change From Baseline of European Quality of Life-5 Dimensions - 3 Levels (EuroQoL-5D-3L ) Index Score and Visual Analog Scale (VAS) Health State Score at Week 26 | Change from Baseline VAS Health State Score | 3.66 units on a scale | Standard Error 0.9 |
Secondary
Change From Baseline to 12 Weeks in Hemoglobin A1c (HbA1c)
Hemoglobin A1c (HbA1c) is a test that measures a participant's average blood glucose level over the past 2 to 3 months.LS means were calculated using a MMRM with baseline HbA1C measurement, stratification factors (country, HbA1c, LDL-C \[\< 100 mg/dL and ≥ 100 mg/dL\], and SU/meglitinide use), treatment, visit, and treatment-by-visit interaction as fixed effects.
Time frame: Baseline, Week 12
Population: All participants who were randomized and received at least 1 dose of study drug and had evaluable HbA1c data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Insulin Peglispro | Change From Baseline to 12 Weeks in Hemoglobin A1c (HbA1c) | -1.43 percent of HbA1c | Standard Error 0.05 |
| Insulin Glargine | Change From Baseline to 12 Weeks in Hemoglobin A1c (HbA1c) | -1.22 percent of HbA1c | Standard Error 0.05 |
Secondary
Change From Baseline to 26 Weeks in Adult Low Blood Sugar Survey (LBSS) Scores
LBSS is a validated, participant-reported 33-item questionnaire with items rated on a 5-point Likert scale, where 0 = never and 5 - always. The LBSS measures behaviors to avoid hypoglycemia and its negative consequences (15 items) and worries about hypoglycemia and its negative consequences (18 items). Total score is the sum of all items (range 0 to 132). Higher total scores reflect greater fear of hypoglycemia. Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) with country, treatment and metformin use as fixed effects and baseline score as a covariate. LBSS was assessed during screening visit (baseline) and again at Week 26.
Time frame: Baseline, Week 26
Population: All participants who were randomized and received at least 1 dose of study drug and had evaluable LBSS data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Insulin Peglispro | Change From Baseline to 26 Weeks in Adult Low Blood Sugar Survey (LBSS) Scores | 1.51 units on a scale | Standard Error 0.69 |
| Insulin Glargine | Change From Baseline to 26 Weeks in Adult Low Blood Sugar Survey (LBSS) Scores | 1.62 units on a scale | Standard Error 0.68 |
Secondary
Change From Baseline to Week 26 in Body Weight
LS Means were calculated using MMRM analysis adjusting for baseline, treatment, stratification factor (region, HbA1c, LDL-C, and SU/meglitinide use), visit and treatment-by-visit interaction.
Time frame: Baseline, Week 26
Population: All participants who were randomized and received at least 1 dose of study drug and had evaluable body weight data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Insulin Peglispro | Change From Baseline to Week 26 in Body Weight | 1.06 Kilogram (kg) | Standard Error 0.16 |
| Insulin Glargine | Change From Baseline to Week 26 in Body Weight | 1.57 Kilogram (kg) | Standard Error 0.16 |
Secondary
Concentration of Triglycerides, Total Cholesterol, Low-Density Lipoprotein (LDL-C), and High-Density Lipoprotein Cholesterol (HDL-C) at Week 26
LS means were calculated using MMRM analysis adjusting for baseline, treatment, stratification factor (region, HbA1c, LDL-C, and SU/meglitinide use), visit, and treatment-by-visit interaction.
Time frame: Week 26
Population: All participants who were randomized and received at least 1 dose of study drug and had evaluable laboratory data.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Peglispro | Concentration of Triglycerides, Total Cholesterol, Low-Density Lipoprotein (LDL-C), and High-Density Lipoprotein Cholesterol (HDL-C) at Week 26 | Cholesterol Wk26 | 175.76 mg/dL | Standard Error 1.65 |
| Insulin Peglispro | Concentration of Triglycerides, Total Cholesterol, Low-Density Lipoprotein (LDL-C), and High-Density Lipoprotein Cholesterol (HDL-C) at Week 26 | Triglycerides Wk26 | 132.43 mg/dL | Standard Error 4.71 |
| Insulin Peglispro | Concentration of Triglycerides, Total Cholesterol, Low-Density Lipoprotein (LDL-C), and High-Density Lipoprotein Cholesterol (HDL-C) at Week 26 | LDL Wk26 | 97.95 mg/dL | Standard Error 1.48 |
| Insulin Peglispro | Concentration of Triglycerides, Total Cholesterol, Low-Density Lipoprotein (LDL-C), and High-Density Lipoprotein Cholesterol (HDL-C) at Week 26 | HDL Wk26 | 51.64 mg/dL | Standard Error 0.49 |
| Insulin Glargine | Concentration of Triglycerides, Total Cholesterol, Low-Density Lipoprotein (LDL-C), and High-Density Lipoprotein Cholesterol (HDL-C) at Week 26 | LDL Wk26 | 101.07 mg/dL | Standard Error 1.46 |
| Insulin Glargine | Concentration of Triglycerides, Total Cholesterol, Low-Density Lipoprotein (LDL-C), and High-Density Lipoprotein Cholesterol (HDL-C) at Week 26 | Cholesterol Wk26 | 177.90 mg/dL | Standard Error 1.63 |
| Insulin Glargine | Concentration of Triglycerides, Total Cholesterol, Low-Density Lipoprotein (LDL-C), and High-Density Lipoprotein Cholesterol (HDL-C) at Week 26 | HDL Wk26 | 52.99 mg/dL | Standard Error 0.48 |
| Insulin Glargine | Concentration of Triglycerides, Total Cholesterol, Low-Density Lipoprotein (LDL-C), and High-Density Lipoprotein Cholesterol (HDL-C) at Week 26 | Triglycerides Wk26 | 122.83 mg/dL | Standard Error 4.65 |
Secondary
Fasting Blood Glucose (FBG)
LS Means were calculated using MMRM analysis adjusting for baseline, treatment, stratification factor (region, HbA1c, LDL-C, and SU/meglitinide use), visit and treatment-by-visit interaction.
Time frame: Weeks 0 and 26
Population: All participants who were randomized and received at least 1 dose of study drug and had evaluable FBG data.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Peglispro | Fasting Blood Glucose (FBG) | Week 0 | 159.53 mg/dL | Standard Error 2.51 |
| Insulin Peglispro | Fasting Blood Glucose (FBG) | Week 26 | 108.39 mg/dL | Standard Error 1.58 |
| Insulin Glargine | Fasting Blood Glucose (FBG) | Week 0 | 161.19 mg/dL | Standard Error 2.48 |
| Insulin Glargine | Fasting Blood Glucose (FBG) | Week 26 | 108.22 mg/dL | Standard Error 1.55 |
Secondary
Fasting Serum Glucose (FSG)
LS means were calculated using MMRM analysis adjusting for baseline, treatment, stratification factor (region, HbA1c, LDL-C, and sulfonylurea \[SU\]/meglitinide use), visit, and treatment-by-visit interaction.
Time frame: Weeks 0 and 26
Population: All participants who were randomized and received at least 1 dose of study drug and had evaluable FSG data.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Peglispro | Fasting Serum Glucose (FSG) | Week 26 | 103.85 mg/dL | Standard Error 1.93 |
| Insulin Peglispro | Fasting Serum Glucose (FSG) | Week 0 | 164.31 mg/dL | Standard Error 2.78 |
| Insulin Glargine | Fasting Serum Glucose (FSG) | Week 0 | 166.61 mg/dL | Standard Error 2.76 |
| Insulin Glargine | Fasting Serum Glucose (FSG) | Week 26 | 110.32 mg/dL | Standard Error 1.9 |
Secondary
Insulin Dose Per Kilogram (kg) of Body Weight
LS means were calculated using MMRM analysis adjusting for baseline, treatment, stratification factor (region, HbA1c, LDL-C, and SU/meglitinide), visit, and treatment-by-visit interaction.
Time frame: Week 26
Population: All participants who were randomized and received at least 1 dose of study drug and had evaluable insulin dose and body weight data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Insulin Peglispro | Insulin Dose Per Kilogram (kg) of Body Weight | 0.26 units per kg | Standard Error 0.01 |
| Insulin Glargine | Insulin Dose Per Kilogram (kg) of Body Weight | 0.26 units per kg | Standard Error 0.01 |
Secondary
Insulin Treatment Satisfaction Questionnaire (ITSQ) Score
The Insulin Treatment Satisfaction Questionnaire is a validated instrument containing 22 items that assessed treatment satisfaction for participants with diabetes 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 score on a scale of 0-100, where a higher score indicate better treatment satisfaction. LS means was achieved using a MMRM model for post-baseline measures with stratification factors (country, HbA1c, and SU/meglitinide use) treatment, visit, treatment-by-visit as fixed effects. ITSQ was assessed at Week 4 (baseline) and Week 26.
Time frame: Week 4 and 26
Population: All participants who were randomized and received at least 1 dose of study drug and have evaluable ITSQ data. Missing endpoints were imputed using last observation carried forward (LOCF).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Peglispro | Insulin Treatment Satisfaction Questionnaire (ITSQ) Score | ITSQ Wk4 | 74.13 units on a scale | Standard Error 1.04 |
| Insulin Peglispro | Insulin Treatment Satisfaction Questionnaire (ITSQ) Score | ITSQ Wk26 | 78.73 units on a scale | Standard Error 1.06 |
| Insulin Glargine | Insulin Treatment Satisfaction Questionnaire (ITSQ) Score | ITSQ Wk4 | 75.94 units on a scale | Standard Error 1.03 |
| Insulin Glargine | Insulin Treatment Satisfaction Questionnaire (ITSQ) Score | ITSQ Wk26 | 78.29 units on a scale | Standard Error 1.05 |
Secondary
Intra-Participant Variability of the Fasting Blood Glucose (FBG)
Intra-participant variability of Fasting Blood Glucose (FBG), which was measured by Self Monitored Blood Glucose (SMBG), was assessed by the standard deviation of the FBG measurement at the Week 26 visit. LS means were calculated using a MMRM with baseline fasting blood glucose measurement, stratification factors (country, HbA1c, LDL-C \[\< 100 mg/dL and ≥ 100 mg/dL\], and SU/meglitinide use), treatment, visit, and treatment-by-visit interaction as fixed effects.
Time frame: Week 26
Population: All participants who were randomized and had at least 1 dose of study drug and had evaluable FBG data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Insulin Peglispro | Intra-Participant Variability of the Fasting Blood Glucose (FBG) | 14.97 mg/dL | Standard Error 0.76 |
| Insulin Glargine | Intra-Participant Variability of the Fasting Blood Glucose (FBG) | 15.12 mg/dL | Standard Error 0.75 |
Secondary
Percentage of Participants Achieving Steady-State of Basal Insulin Dose at 26 Weeks (Time to Steady State for Basal Insulin [Stable Maximum Dose])
Time frame: Week 26
Population: All participants who were randomized and received at least 1 dose of study drug and had evaluable insulin dose data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Insulin Peglispro | Percentage of Participants Achieving Steady-State of Basal Insulin Dose at 26 Weeks (Time to Steady State for Basal Insulin [Stable Maximum Dose]) | 96.9 percentage of participants |
| Insulin Glargine | Percentage of Participants Achieving Steady-State of Basal Insulin Dose at 26 Weeks (Time to Steady State for Basal Insulin [Stable Maximum Dose]) | 97.2 percentage of participants |
Secondary
Percentage of Participants With Detectable Anti-Insulin Peglispro Antibodies at Week 26
For participants with detectable anti-insulin peglispro antibody level, the percentage of participants with positive cross-react with endogenous insulin was summarized.
Time frame: Week 26
Population: All participants who were randomized and received at least 1 dose of study drug and had evaluable antibody data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Insulin Peglispro | Percentage of Participants With Detectable Anti-Insulin Peglispro Antibodies at Week 26 | 24.6 percentage of participants |
| Insulin Glargine | Percentage of Participants With Detectable Anti-Insulin Peglispro Antibodies at Week 26 | 32.5 percentage of participants |
Secondary
Percentage of Participants With HbA1c ≤6.5%
Percentage of participants with HbA1c ≤6.5% at Week 26 were made using a logistic regression model for endpoint used last observation carried forward (LOCF) method including treatment, baseline HbA1c value.
Time frame: Week 26
Population: All participants who were randomized and received at least 1 dose of study drug and had evaluable HbA1c data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Insulin Peglispro | Percentage of Participants With HbA1c ≤6.5% | 29.8 Percentage of participants |
| Insulin Glargine | Percentage of Participants With HbA1c ≤6.5% | 22.7 Percentage of participants |
Secondary
Percentage of Participants With Total and Nocturnal Hypoglycemic Events (HE)
Percentage of participants with hypoglycemic events (total or nocturnal) to Week 26 based on BG Threshold 70mg/dL.
Time frame: Baseline to Week 26
Population: All participants who were randomized and received at least 1 dose of study drug and had evaluable HE data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Insulin Peglispro | Percentage of Participants With Total and Nocturnal Hypoglycemic Events (HE) | Nocturnal Hypoglycemia BG 70mg/dL | 26.6 percentage of participants |
| Insulin Peglispro | Percentage of Participants With Total and Nocturnal Hypoglycemic Events (HE) | Total Hypoglycemia BG 70mg/dL | 77.1 percentage of participants |
| Insulin Glargine | Percentage of Participants With Total and Nocturnal Hypoglycemic Events (HE) | Nocturnal Hypoglycemia BG 70mg/dL | 29.6 percentage of participants |
| Insulin Glargine | Percentage of Participants With Total and Nocturnal Hypoglycemic Events (HE) | Total Hypoglycemia BG 70mg/dL | 76.5 percentage of participants |
Secondary
Percent Hemoglobin A1c at Week 26
HbA1c is a test that measures a participant's average blood glucose level over the past 2 to 3 months. LS means were calculated using a MMRM with baseline HbA1C measurement, stratification factors (country, HbA1c, LDL-C \[\< 100 mg/dL and ≥ 100 mg/dL\], and SU/meglitinide use), treatment, visit, and treatment-by-visit interaction as fixed effects.
Time frame: Week 26
Population: All participants who were randomized and received at least 1 dose of study drug and had evaluable HbA1c data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Insulin Peglispro | Percent Hemoglobin A1c at Week 26 | 6.92 percent of HbA1c | Standard Error 0.06 |
| Insulin Glargine | Percent Hemoglobin A1c at Week 26 | 7.17 percent of HbA1c | Standard Error 0.06 |