Type 2 Diabetes Mellitus
Conditions
Keywords
Type 2 diabetes mellitus, Oral antihyperglycemic medications, Long-Term Safety, GLP 1, Glucagon like peptide 1
Brief summary
This was a 52-week, multicenter, non-randomized, open-label, Phase 3 long-term safety study in participants with type 2 diabetes mellitus who have inadequate glycemic control with monotherapy of oral antihyperglycemic medication (OAM).
Interventions
DRUGLY2189265
SU is a pre-study prescribed dose and is not being provided as part of the trial.
DRUGBiguanides (BG)
Biguanides is a pre-study prescribed dose and is not being provided as part of the trial.
DRUGalpha-glucosidase inhibitor (a-GI)
a-GI is a pre-study prescribed dose and is not being provided as part of the trial.
TZD is a pre-study prescribed dose and is not being provided as part of the trial.
DRUGGlinides
Glinides is a pre-study prescribed dose and is not being provided as part of the trial.
Sponsors
Eli Lilly and Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants who have had a diagnosis of type 2 diabetes mellitus before screening * Participants who have been taking SU (Glibenclamide, Gliclazide, Glimepiride), BG, TZD, a-GI or glinides monotherapy for at least 3 months before screening and have been on a stable dose for at least 8 weeks before screening * Participants must have a qualifying HbA1c value of 7.0% to 11.0% at screening * Participants who have a body mass index (BMI) of 18.5 to 35.0 kilograms per meter squared (kg/m\^2)
Exclusion criteria
* Participants who have a diagnosis of type 1 diabetes * Participants who have previously been treated with any other glucagon-like peptide-1 (GLP-1) analog within the 3 months before screening * Participants who are currently taking insulin or have had previous insulin treatment within the 3 months before screening * Participants who have obvious clinical signs or symptoms of pancreatitis, a history of chronic pancreatitis, or acute pancreatitis at screening, as determined by the investigator. Participants who have a serum amylase concentration ≥3 times the upper limit of the reference range and/or a serum lipase concentration ≥2 times the upper limit of the reference range, as determined by the central laboratory at screening * Participants who have self or family history of medullary C-cell hyperplasia, focal hyperplasia, or medullary thyroid carcinoma (MTC)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) | Baseline through 52 Weeks | A TEAE was defined as an event that first occurs or worsens (increases in severity) after baseline, regardless of causality or severity. The percentage of participants with TEAEs was calculated by dividing the number of participants with at least 1 TEAE over the 52-week treatment period by the total number of participants analyzed, multiplied by 100%. A summary of serious and other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events module. |
| Percentage of Participants With Hypoglycemic Episodes | Baseline through 52 Weeks | The percentage of participants with hypoglycemic episodes was calculated by dividing the number of participants with at least 1 hypoglycemic episode over the 52-week treatment period by the total number of participants analyzed, multiplied by 100%. All classifications of hypoglycemia (documented symptomatic, asymptomatic, severe, nocturnal, non-nocturnal, probable symptomatic, relative, and unspecified) were included, except for episodes of relative hypoglycemia that were not severe. A summary of serious and other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events module. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Fasting Blood Glucose (FBG) | Baseline, up to 26 weeks and up to 52 weeks | — |
| Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) | Baseline, up to 26 weeks and up to 52 weeks | Participants were to test and record SMBG concentrations in their study diaries before each meal (breakfast, lunch, and dinner), approximately 2 hours after the start of each meal. For the mean of all 7-point blood glucose values, the daily mean was calculated as the average of 7 blood glucose values collected on a particular day. The mean of all 7-point blood glucose values at each visit was calculated as the average of 2 daily means. The change from baseline was calculated as the mean of all 7-point blood glucose values at endpoint minus the mean of all 7-point blood glucose values at baseline. |
| Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Baseline, up to 26 Weeks and up to 52 Weeks | — |
| Change From Baseline in Updated Homeostasis Model Assessment (HOMA2) | Baseline, up to 26 weeks and up to 52 weeks | The HOMA2 is a computer model that uses fasting plasma insulin and glucose concentrations to estimate steady state pancreatic beta cell function (%B) and to estimate insulin sensitivity (%S) as a percentage of a normal reference population (normal young adults). The normal reference population was set at 100%. The change from baseline for fasting insulin concentrations are presented as insulin secretion (HOMA2-%B) and insulin sensitivity (HOMA2-%S). |
| Change From Baseline in Body Weight | Baseline, up to 26 weeks and up to 52 weeks | — |
| Percentage of Participants Who Achieve HbA1c ≤6.5% or <7% | 26 weeks and 52 weeks | — |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| LY2189265 + SU LY2189265: 0.75 mg administered SC, once weekly for 52 weeks
Participants were to continue on their stable, pre-study, physician-prescribed dose of SU monotherapy throughout the study. | 131 |
| LY2189265 + BG LY2189265: 0.75 mg administered SC, once weekly for 52 weeks
Participants were to continue on their stable, pre-study, physician-prescribed dose of BG monotherapy throughout the study. | 61 |
| LY2189265 + a-GI LY2189265: 0.75 mg administered SC, once weekly for 52 weeks
Participants were to continue on their stable, pre-study, physician-prescribed dose of a-GI monotherapy throughout the study. | 65 |
| LY2189265 + TZD LY2189265: 0.75 mg administered SC, once weekly for 52 weeks
Participants were to continue on their stable, pre-study, physician-prescribed dose of TZD monotherapy throughout the study. | 66 |
| LY2189265 + Glinides LY2189265: 0.75 mg administered SC, once weekly for 52 weeks
Participants were to continue on their stable, pre-study, physician-prescribed dose of glinides monotherapy throughout the study. | 71 |
| Total | 394 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 8 | 1 | 6 | 2 | 2 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 | 0 | 1 |
| Overall Study | Physician Decision | 0 | 0 | 0 | 1 | 1 |
| Overall Study | Protocol Violation | 2 | 0 | 1 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | LY2189265 + SU | Total | LY2189265 + Glinides | LY2189265 + TZD | LY2189265 + a-GI | LY2189265 + BG |
|---|---|---|---|---|---|---|
| Age, Continuous | 58.68 years STANDARD_DEVIATION 11.59 | 57.35 years STANDARD_DEVIATION 10.96 | 58.17 years STANDARD_DEVIATION 10.3 | 56.40 years STANDARD_DEVIATION 10.51 | 59.13 years STANDARD_DEVIATION 10.51 | 52.69 years STANDARD_DEVIATION 10.19 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 131 Participants | 394 Participants | 71 Participants | 66 Participants | 65 Participants | 61 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Japan | 131 participants | 394 participants | 71 participants | 66 participants | 65 participants | 61 participants |
| Sex: Female, Male Female | 36 Participants | 98 Participants | 17 Participants | 14 Participants | 10 Participants | 21 Participants |
| Sex: Female, Male Male | 95 Participants | 296 Participants | 54 Participants | 52 Participants | 55 Participants | 40 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 |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 112 / 131 | 51 / 61 | 46 / 65 | 53 / 66 | 52 / 71 |
| serious Total, serious adverse events | 9 / 131 | 3 / 61 | 4 / 65 | 1 / 66 | 3 / 71 |
Outcome results
Primary
Percentage of Participants With Hypoglycemic Episodes
The percentage of participants with hypoglycemic episodes was calculated by dividing the number of participants with at least 1 hypoglycemic episode over the 52-week treatment period by the total number of participants analyzed, multiplied by 100%. All classifications of hypoglycemia (documented symptomatic, asymptomatic, severe, nocturnal, non-nocturnal, probable symptomatic, relative, and unspecified) were included, except for episodes of relative hypoglycemia that were not severe. A summary of serious and other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events module.
Time frame: Baseline through 52 Weeks
Population: All enrolled participants who received at least 1 dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LY2189265 + SU | Percentage of Participants With Hypoglycemic Episodes | 33.6 percentage of participants |
| LY2189265 + BG | Percentage of Participants With Hypoglycemic Episodes | 3.3 percentage of participants |
| LY2189265 + a-GI | Percentage of Participants With Hypoglycemic Episodes | 6.2 percentage of participants |
| LY2189265 + TZD | Percentage of Participants With Hypoglycemic Episodes | 6.1 percentage of participants |
| LY2189265 + Glinides | Percentage of Participants With Hypoglycemic Episodes | 9.9 percentage of participants |
Primary
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)
A TEAE was defined as an event that first occurs or worsens (increases in severity) after baseline, regardless of causality or severity. The percentage of participants with TEAEs was calculated by dividing the number of participants with at least 1 TEAE over the 52-week treatment period by the total number of participants analyzed, multiplied by 100%. A summary of serious and other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events module.
Time frame: Baseline through 52 Weeks
Population: All enrolled participants who received at least 1 dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LY2189265 + SU | Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) | 85.5 percentage of participants |
| LY2189265 + BG | Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) | 83.6 percentage of participants |
| LY2189265 + a-GI | Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) | 70.8 percentage of participants |
| LY2189265 + TZD | Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) | 80.3 percentage of participants |
| LY2189265 + Glinides | Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) | 73.2 percentage of participants |
Secondary
Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG)
Participants were to test and record SMBG concentrations in their study diaries before each meal (breakfast, lunch, and dinner), approximately 2 hours after the start of each meal. For the mean of all 7-point blood glucose values, the daily mean was calculated as the average of 7 blood glucose values collected on a particular day. The mean of all 7-point blood glucose values at each visit was calculated as the average of 2 daily means. The change from baseline was calculated as the mean of all 7-point blood glucose values at endpoint minus the mean of all 7-point blood glucose values at baseline.
Time frame: Baseline, up to 26 weeks and up to 52 weeks
Population: Participants who were randomized and received at least 1 dose of study drug with evaluable SMBG data. LOCF was used to impute missing postbaseline. values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LY2189265 + SU | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) | Pre-midday meal at 52 Weeks (n=131,61,65,66,71) | -43.90 mg/dL | Standard Error 5.15 |
| LY2189265 + SU | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) | 2hr postmidday meal at 26 Weeks(n=131,60,65,66,71) | -67.24 mg/dL | Standard Error 5.24 |
| LY2189265 + SU | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) | 2hr postmidday meal at 52 Weeks(n=131,60,65,66,71) | -57.27 mg/dL | Standard Error 5.44 |
| LY2189265 + SU | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) | Bedtime at 52 Weeks (n=128, 61, 65, 63, 67) | -54.07 mg/dL | Standard Error 5.24 |
| LY2189265 + SU | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) | Pre-evening meal at 26 Weeks (n=130,61,65,66,70) | -44.57 mg/dL | Standard Error 5.63 |
| LY2189265 + SU | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) | Pre-morning mean at 52 Weeks (n=131,61,64,66,71) | -42.93 mg/dL | Standard Error 3.89 |
| LY2189265 + SU | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) | 2hr postevening meal at 52Weeks(n=128,61,65,66,69) | -58.98 mg/dL | Standard Error 5.71 |
| LY2189265 + SU | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) | Pre-morning mean at 26 Weeks (n=131,61,64,66,71) | -44.70 mg/dL | Standard Error 4.57 |
| LY2189265 + SU | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) | Pre-evening meal at 52 Weeks (n=130,61,65,66,70) | -43.90 mg/dL | Standard Error 5.39 |
| LY2189265 + SU | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) | 2hr postmorning meal at 26Weeks(n=131,61,65,66,71) | -69.66 mg/dL | Standard Error 5.69 |
| LY2189265 + SU | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) | 2hr postmorning meal at 52Weeks(n=131,61,65,66,71) | -58.50 mg/dL | Standard Error 5.63 |
| LY2189265 + SU | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) | 2hr postevening meal at 26Weeks(n=128,61,65,66,69) | -62.24 mg/dL | Standard Error 6.05 |
| LY2189265 + SU | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) | Bedtime at 26 Weeks (n=128, 61, 65, 63, 67) | -61.07 mg/dL | Standard Error 5.08 |
| LY2189265 + SU | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) | Pre-midday meal at 26 Weeks (n=131,61,65,66,71) | -49.95 mg/dL | Standard Error 4.85 |
| LY2189265 + BG | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) | Pre-midday meal at 26 Weeks (n=131,61,65,66,71) | -26.26 mg/dL | Standard Error 4.93 |
| LY2189265 + BG | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) | Pre-midday meal at 52 Weeks (n=131,61,65,66,71) | -33.34 mg/dL | Standard Error 5.12 |
| LY2189265 + BG | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) | Pre-evening meal at 52 Weeks (n=130,61,65,66,70) | -25.34 mg/dL | Standard Error 5.55 |
| LY2189265 + BG | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) | Pre-morning mean at 26 Weeks (n=131,61,64,66,71) | -34.60 mg/dL | Standard Error 3.88 |
| LY2189265 + BG | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) | Pre-morning mean at 52 Weeks (n=131,61,64,66,71) | -37.19 mg/dL | Standard Error 3.83 |
| LY2189265 + BG | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) | 2hr postmidday meal at 26 Weeks(n=131,60,65,66,71) | -50.03 mg/dL | Standard Error 5.7 |
| LY2189265 + BG | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) | 2hr postmorning meal at 52Weeks(n=131,61,65,66,71) | -63.81 mg/dL | Standard Error 7.22 |
| LY2189265 + BG | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) | Bedtime at 52 Weeks (n=128, 61, 65, 63, 67) | -52.70 mg/dL | Standard Error 6.45 |
| LY2189265 + BG | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) | Pre-evening meal at 26 Weeks (n=130,61,65,66,70) | -25.66 mg/dL | Standard Error 5.28 |
| LY2189265 + BG | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) | 2hr postmorning meal at 26Weeks(n=131,61,65,66,71) | -64.23 mg/dL | Standard Error 6.35 |
| LY2189265 + BG | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) | Bedtime at 26 Weeks (n=128, 61, 65, 63, 67) | -49.98 mg/dL | Standard Error 6.48 |
| LY2189265 + BG | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) | 2hr postmidday meal at 52 Weeks(n=131,60,65,66,71) | -52.70 mg/dL | Standard Error 5.26 |
| LY2189265 + BG | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) | 2hr postevening meal at 52Weeks(n=128,61,65,66,69) | -48.61 mg/dL | Standard Error 6.45 |
| LY2189265 + BG | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) | 2hr postevening meal at 26Weeks(n=128,61,65,66,69) | -45.41 mg/dL | Standard Error 6.71 |
| LY2189265 + a-GI | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) | 2hr postevening meal at 52Weeks(n=128,61,65,66,69) | -63.82 mg/dL | Standard Error 7 |
| LY2189265 + a-GI | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) | Pre-evening meal at 26 Weeks (n=130,61,65,66,70) | -57.82 mg/dL | Standard Error 6.83 |
| LY2189265 + a-GI | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) | Pre-evening meal at 52 Weeks (n=130,61,65,66,70) | -54.66 mg/dL | Standard Error 7.35 |
| LY2189265 + a-GI | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) | Pre-morning mean at 26 Weeks (n=131,61,64,66,71) | -45.97 mg/dL | Standard Error 4.99 |
| LY2189265 + a-GI | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) | 2hr postevening meal at 26Weeks(n=128,61,65,66,69) | -71.15 mg/dL | Standard Error 7.57 |
| LY2189265 + a-GI | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) | Pre-morning mean at 52 Weeks (n=131,61,64,66,71) | -45.69 mg/dL | Standard Error 5.05 |
| LY2189265 + a-GI | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) | Pre-midday meal at 26 Weeks (n=131,61,65,66,71) | -54.75 mg/dL | Standard Error 6.24 |
| LY2189265 + a-GI | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) | Bedtime at 26 Weeks (n=128, 61, 65, 63, 67) | -63.98 mg/dL | Standard Error 6.9 |
| LY2189265 + a-GI | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) | 2hr postmorning meal at 52Weeks(n=131,61,65,66,71) | -73.62 mg/dL | Standard Error 7.27 |
| LY2189265 + a-GI | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) | 2hr postmorning meal at 26Weeks(n=131,61,65,66,71) | -73.43 mg/dL | Standard Error 6.7 |
| LY2189265 + a-GI | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) | Pre-midday meal at 52 Weeks (n=131,61,65,66,71) | -55.96 mg/dL | Standard Error 6.42 |
| LY2189265 + a-GI | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) | Bedtime at 52 Weeks (n=128, 61, 65, 63, 67) | -66.74 mg/dL | Standard Error 7.31 |
| LY2189265 + a-GI | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) | 2hr postmidday meal at 26 Weeks(n=131,60,65,66,71) | -67.70 mg/dL | Standard Error 7.37 |
| LY2189265 + a-GI | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) | 2hr postmidday meal at 52 Weeks(n=131,60,65,66,71) | -63.47 mg/dL | Standard Error 7.12 |
| LY2189265 + TZD | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) | 2hr postevening meal at 26Weeks(n=128,61,65,66,69) | -66.14 mg/dL | Standard Error 8.22 |
| LY2189265 + TZD | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) | 2hr postmorning meal at 26Weeks(n=131,61,65,66,71) | -65.73 mg/dL | Standard Error 5.94 |
| LY2189265 + TZD | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) | Pre-midday meal at 26 Weeks (n=131,61,65,66,71) | -51.80 mg/dL | Standard Error 6.68 |
| LY2189265 + TZD | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) | Pre-morning mean at 26 Weeks (n=131,61,64,66,71) | -35.40 mg/dL | Standard Error 3.85 |
| LY2189265 + TZD | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) | Pre-morning mean at 52 Weeks (n=131,61,64,66,71) | -39.83 mg/dL | Standard Error 4.24 |
| LY2189265 + TZD | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) | 2hr postmorning meal at 52Weeks(n=131,61,65,66,71) | -67.51 mg/dL | Standard Error 6.49 |
| LY2189265 + TZD | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) | Pre-midday meal at 52 Weeks (n=131,61,65,66,71) | -50.21 mg/dL | Standard Error 7.04 |
| LY2189265 + TZD | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) | 2hr postmidday meal at 26 Weeks(n=131,60,65,66,71) | -80.02 mg/dL | Standard Error 7.93 |
| LY2189265 + TZD | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) | 2hr postmidday meal at 52 Weeks(n=131,60,65,66,71) | -81.64 mg/dL | Standard Error 8.68 |
| LY2189265 + TZD | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) | Pre-evening meal at 26 Weeks (n=130,61,65,66,70) | -43.22 mg/dL | Standard Error 7.53 |
| LY2189265 + TZD | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) | Pre-evening meal at 52 Weeks (n=130,61,65,66,70) | -42.15 mg/dL | Standard Error 7.44 |
| LY2189265 + TZD | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) | 2hr postevening meal at 52Weeks(n=128,61,65,66,69) | -69.30 mg/dL | Standard Error 8.6 |
| LY2189265 + TZD | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) | Bedtime at 26 Weeks (n=128, 61, 65, 63, 67) | -66.19 mg/dL | Standard Error 8.75 |
| LY2189265 + TZD | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) | Bedtime at 52 Weeks (n=128, 61, 65, 63, 67) | -68.42 mg/dL | Standard Error 9.05 |
| LY2189265 + Glinides | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) | 2hr postmidday meal at 52 Weeks(n=131,60,65,66,71) | -65.46 mg/dL | Standard Error 7.23 |
| LY2189265 + Glinides | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) | 2hr postmidday meal at 26 Weeks(n=131,60,65,66,71) | -68.49 mg/dL | Standard Error 7.84 |
| LY2189265 + Glinides | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) | Pre-midday meal at 26 Weeks (n=131,61,65,66,71) | -54.51 mg/dL | Standard Error 5.79 |
| LY2189265 + Glinides | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) | 2hr postevening meal at 52Weeks(n=128,61,65,66,69) | -64.22 mg/dL | Standard Error 7.07 |
| LY2189265 + Glinides | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) | 2hr postmorning meal at 52Weeks(n=131,61,65,66,71) | -73.78 mg/dL | Standard Error 7.95 |
| LY2189265 + Glinides | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) | 2hr postmorning meal at 26Weeks(n=131,61,65,66,71) | -67.99 mg/dL | Standard Error 7.24 |
| LY2189265 + Glinides | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) | Pre-morning mean at 52 Weeks (n=131,61,64,66,71) | -46.45 mg/dL | Standard Error 4.3 |
| LY2189265 + Glinides | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) | Bedtime at 52 Weeks (n=128, 61, 65, 63, 67) | -64.41 mg/dL | Standard Error 6.21 |
| LY2189265 + Glinides | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) | Bedtime at 26 Weeks (n=128, 61, 65, 63, 67) | -64.01 mg/dL | Standard Error 6.56 |
| LY2189265 + Glinides | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) | Pre-morning mean at 26 Weeks (n=131,61,64,66,71) | -48.26 mg/dL | Standard Error 4.33 |
| LY2189265 + Glinides | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) | Pre-midday meal at 52 Weeks (n=131,61,65,66,71) | -56.07 mg/dL | Standard Error 5.6 |
| LY2189265 + Glinides | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) | Pre-evening meal at 52 Weeks (n=130,61,65,66,70) | -51.64 mg/dL | Standard Error 6.1 |
| LY2189265 + Glinides | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) | 2hr postevening meal at 26Weeks(n=128,61,65,66,69) | -68.75 mg/dL | Standard Error 7.88 |
| LY2189265 + Glinides | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) | Pre-evening meal at 26 Weeks (n=130,61,65,66,70) | -46.85 mg/dL | Standard Error 5.88 |
Comparison: Pre-morning meal at 26 Weeksp-value: <0.00195% CI: [-46.55, -38.29]t-test, 2 sided
Comparison: Pre-morning meal at 52 Weeksp-value: <0.00195% CI: [-46.44, -38.76]t-test, 2 sided
Comparison: 2 hours post-morning meal at 26 Weeksp-value: <0.00195% CI: [-74.18, -62.79]t-test, 2 sided
Comparison: 2 hours post-morning meal at 52 Weeksp-value: <0.00195% CI: [-72.12, -60.04]t-test, 2 sided
Comparison: Pre-midday meal at 26 Weeksp-value: <0.00195% CI: [-53.32, -43.09]t-test, 2 sided
Comparison: Pre-midday meal at 52 Weeksp-value: <0.00195% CI: [-52.77, -42.24]t-test, 2 sided
Comparison: 2 hours post-midday meal at 26 Weeksp-value: <0.00195% CI: [-73.02, -61.11]t-test, 2 sided
Comparison: 2 hours post-midday meal at 52 Weeksp-value: <0.00195% CI: [-69.16, -57.18]t-test, 2 sided
Comparison: Pre-evening meal at 26 Weeksp-value: <0.00195% CI: [-49.67, -38.34]t-test, 2 sided
Comparison: Pre-evening meal at 52 Weeksp-value: <0.00195% CI: [-49.55, -38.21]t-test, 2 sided
Comparison: 2 hours post-evening meal at 26 Weeksp-value: <0.00195% CI: [-69.32, -56.5]t-test, 2 sided
Comparison: 2 hours post-evening meal at 52 Weeksp-value: <0.00195% CI: [-66.95, -54.74]t-test, 2 sided
Comparison: Bedtime meal at 26 Weeksp-value: <0.00195% CI: [-66.93, -55.37]t-test, 2 sided
Comparison: Bedtime meal at 52 Weeksp-value: <0.00195% CI: [-66.07, -54.25]t-test, 2 sided
Secondary
Change From Baseline in Body Weight
Time frame: Baseline, up to 26 weeks and up to 52 weeks
Population: Participants who were randomized and received at least 1 dose of study drug with evaluable body weight data. LOCF was used to impute missing postbaseline values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LY2189265 + SU | Change From Baseline in Body Weight | 52 Weeks | 0.10 kilograms (kg) | Standard Error 0.24 |
| LY2189265 + SU | Change From Baseline in Body Weight | 26 Weeks | 0.02 kilograms (kg) | Standard Error 0.22 |
| LY2189265 + BG | Change From Baseline in Body Weight | 52 Weeks | -0.87 kilograms (kg) | Standard Error 0.4 |
| LY2189265 + BG | Change From Baseline in Body Weight | 26 Weeks | -0.74 kilograms (kg) | Standard Error 0.39 |
| LY2189265 + a-GI | Change From Baseline in Body Weight | 52 Weeks | -1.24 kilograms (kg) | Standard Error 0.42 |
| LY2189265 + a-GI | Change From Baseline in Body Weight | 26 Weeks | -1.22 kilograms (kg) | Standard Error 0.33 |
| LY2189265 + TZD | Change From Baseline in Body Weight | 26 Weeks | 0.78 kilograms (kg) | Standard Error 0.3 |
| LY2189265 + TZD | Change From Baseline in Body Weight | 52 Weeks | 1.02 kilograms (kg) | Standard Error 0.35 |
| LY2189265 + Glinides | Change From Baseline in Body Weight | 52 Weeks | 0.04 kilograms (kg) | Standard Error 0.26 |
| LY2189265 + Glinides | Change From Baseline in Body Weight | 26 Weeks | 0.19 kilograms (kg) | Standard Error 0.25 |
Comparison: Body weight at 26 Weeksp-value: <0.27795% CI: [-0.4, 0.12]t-test, 2 sided
Comparison: Body weight at 52 Weeksp-value: 0.38295% CI: [-0.42, 0.16]t-test, 2 sided
Secondary
Change From Baseline in Fasting Blood Glucose (FBG)
Time frame: Baseline, up to 26 weeks and up to 52 weeks
Population: Participants who were randomized and received at least 1 dose of study drug with evaluable FBG data. LOCF was used to impute missing postbaseline values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LY2189265 + SU | Change From Baseline in Fasting Blood Glucose (FBG) | 52 Weeks | -43.2 milligrams/deciliters (mg/dL) | Standard Error 3.8 |
| LY2189265 + SU | Change From Baseline in Fasting Blood Glucose (FBG) | 26 Weeks | -46.8 milligrams/deciliters (mg/dL) | Standard Error 4.2 |
| LY2189265 + BG | Change From Baseline in Fasting Blood Glucose (FBG) | 26 Weeks | -37.9 milligrams/deciliters (mg/dL) | Standard Error 4 |
| LY2189265 + BG | Change From Baseline in Fasting Blood Glucose (FBG) | 52 Weeks | -36.0 milligrams/deciliters (mg/dL) | Standard Error 4.2 |
| LY2189265 + a-GI | Change From Baseline in Fasting Blood Glucose (FBG) | 52 Weeks | -47.0 milligrams/deciliters (mg/dL) | Standard Error 4.7 |
| LY2189265 + a-GI | Change From Baseline in Fasting Blood Glucose (FBG) | 26 Weeks | -46.8 milligrams/deciliters (mg/dL) | Standard Error 4.7 |
| LY2189265 + TZD | Change From Baseline in Fasting Blood Glucose (FBG) | 26 Weeks | -42.1 milligrams/deciliters (mg/dL) | Standard Error 4.5 |
| LY2189265 + TZD | Change From Baseline in Fasting Blood Glucose (FBG) | 52 Weeks | -39.6 milligrams/deciliters (mg/dL) | Standard Error 5 |
| LY2189265 + Glinides | Change From Baseline in Fasting Blood Glucose (FBG) | 52 Weeks | -45.8 milligrams/deciliters (mg/dL) | Standard Error 4 |
| LY2189265 + Glinides | Change From Baseline in Fasting Blood Glucose (FBG) | 26 Weeks | -42.7 milligrams/deciliters (mg/dL) | Standard Error 3.9 |
Comparison: FBG at 26 Weeksp-value: <0.00195% CI: [-47.8, -40]t-test, 2 sided
Comparison: FBG at 52 Weeksp-value: <0.00195% CI: [-46.4, -38.7]t-test, 2 sided
Secondary
Change From Baseline in Glycosylated Hemoglobin (HbA1c)
Time frame: Baseline, up to 26 Weeks and up to 52 Weeks
Population: Participants who were randomized and received at least 1 dose of study drug with evaluable HbA1c data. Last observation carried forward (LOCF) was used to impute missing postbaseline values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LY2189265 + SU | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | 26 Weeks | -1.93 percentage of HbA1c | Standard Error 0.09 |
| LY2189265 + SU | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | 52 Weeks | -1.67 percentage of HbA1c | Standard Error 0.09 |
| LY2189265 + BG | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | 26 Weeks | -1.58 percentage of HbA1c | Standard Error 0.11 |
| LY2189265 + BG | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | 52 Weeks | -1.57 percentage of HbA1c | Standard Error 0.11 |
| LY2189265 + a-GI | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | 26 Weeks | -1.67 percentage of HbA1c | Standard Error 0.1 |
| LY2189265 + a-GI | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | 52 Weeks | -1.65 percentage of HbA1c | Standard Error 0.11 |
| LY2189265 + TZD | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | 52 Weeks | -1.69 percentage of HbA1c | Standard Error 0.13 |
| LY2189265 + TZD | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | 26 Weeks | -1.71 percentage of HbA1c | Standard Error 0.13 |
| LY2189265 + Glinides | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | 26 Weeks | -1.80 percentage of HbA1c | Standard Error 0.12 |
| LY2189265 + Glinides | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | 52 Weeks | -1.65 percentage of HbA1c | Standard Error 0.13 |
Comparison: HbA1c at 26 Weeksp-value: <0.00195% CI: [-1.87, -1.67]t-test, 2 sided
Comparison: HbA1c at 52 Weeksp-value: <0.00195% CI: [-1.75, -1.55]t-test, 2 sided
Secondary
Change From Baseline in Updated Homeostasis Model Assessment (HOMA2)
The HOMA2 is a computer model that uses fasting plasma insulin and glucose concentrations to estimate steady state pancreatic beta cell function (%B) and to estimate insulin sensitivity (%S) as a percentage of a normal reference population (normal young adults). The normal reference population was set at 100%. The change from baseline for fasting insulin concentrations are presented as insulin secretion (HOMA2-%B) and insulin sensitivity (HOMA2-%S).
Time frame: Baseline, up to 26 weeks and up to 52 weeks
Population: Participants who were randomized and received at least 1 dose of study drug with evaluable HOMA2 data. LOCF was used to impute missing postbaseline values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LY2189265 + SU | Change From Baseline in Updated Homeostasis Model Assessment (HOMA2) | HOMA2-%B, 26 Weeks | 29.10 percentage of HOMA2 | Standard Error 2.75 |
| LY2189265 + SU | Change From Baseline in Updated Homeostasis Model Assessment (HOMA2) | HOMA2-%B, 52 Weeks | 26.06 percentage of HOMA2 | Standard Error 2.77 |
| LY2189265 + SU | Change From Baseline in Updated Homeostasis Model Assessment (HOMA2) | HOMA2-%S, 26 Weeks | -4.80 percentage of HOMA2 | Standard Error 3.4 |
| LY2189265 + SU | Change From Baseline in Updated Homeostasis Model Assessment (HOMA2) | HOMA2-%S, 52 Weeks | -3.99 percentage of HOMA2 | Standard Error 3.18 |
| LY2189265 + BG | Change From Baseline in Updated Homeostasis Model Assessment (HOMA2) | HOMA2-%B, 26 Weeks | 28.15 percentage of HOMA2 | Standard Error 2.79 |
| LY2189265 + BG | Change From Baseline in Updated Homeostasis Model Assessment (HOMA2) | HOMA2-%S, 52 Weeks | -3.83 percentage of HOMA2 | Standard Error 4.89 |
| LY2189265 + BG | Change From Baseline in Updated Homeostasis Model Assessment (HOMA2) | HOMA2-%B, 52 Weeks | 26.05 percentage of HOMA2 | Standard Error 2.97 |
| LY2189265 + BG | Change From Baseline in Updated Homeostasis Model Assessment (HOMA2) | HOMA2-%S, 26 Weeks | -3.48 percentage of HOMA2 | Standard Error 4.39 |
| LY2189265 + a-GI | Change From Baseline in Updated Homeostasis Model Assessment (HOMA2) | HOMA2-%S, 52 Weeks | 6.86 percentage of HOMA2 | Standard Error 5.24 |
| LY2189265 + a-GI | Change From Baseline in Updated Homeostasis Model Assessment (HOMA2) | HOMA2-%B, 52 Weeks | 28.06 percentage of HOMA2 | Standard Error 3.61 |
| LY2189265 + a-GI | Change From Baseline in Updated Homeostasis Model Assessment (HOMA2) | HOMA2-%S, 26 Weeks | 7.57 percentage of HOMA2 | Standard Error 5.6 |
| LY2189265 + a-GI | Change From Baseline in Updated Homeostasis Model Assessment (HOMA2) | HOMA2-%B, 26 Weeks | 30.88 percentage of HOMA2 | Standard Error 3.25 |
| LY2189265 + TZD | Change From Baseline in Updated Homeostasis Model Assessment (HOMA2) | HOMA2-%B, 26 Weeks | 27.34 percentage of HOMA2 | Standard Error 2.6 |
| LY2189265 + TZD | Change From Baseline in Updated Homeostasis Model Assessment (HOMA2) | HOMA2-%B, 52 Weeks | 25.38 percentage of HOMA2 | Standard Error 2.53 |
| LY2189265 + TZD | Change From Baseline in Updated Homeostasis Model Assessment (HOMA2) | HOMA2-%S, 52 Weeks | 0.47 percentage of HOMA2 | Standard Error 5.87 |
| LY2189265 + TZD | Change From Baseline in Updated Homeostasis Model Assessment (HOMA2) | HOMA2-%S, 26 Weeks | -5.50 percentage of HOMA2 | Standard Error 5.21 |
| LY2189265 + Glinides | Change From Baseline in Updated Homeostasis Model Assessment (HOMA2) | HOMA2-%S, 52 Weeks | -5.51 percentage of HOMA2 | Standard Error 4.71 |
| LY2189265 + Glinides | Change From Baseline in Updated Homeostasis Model Assessment (HOMA2) | HOMA2-%S, 26 Weeks | -4.41 percentage of HOMA2 | Standard Error 4.05 |
| LY2189265 + Glinides | Change From Baseline in Updated Homeostasis Model Assessment (HOMA2) | HOMA2-%B, 52 Weeks | 33.51 percentage of HOMA2 | Standard Error 3.81 |
| LY2189265 + Glinides | Change From Baseline in Updated Homeostasis Model Assessment (HOMA2) | HOMA2-%B, 26 Weeks | 26.93 percentage of HOMA2 | Standard Error 2.59 |
Comparison: HOMA2-B% at 26 Weeksp-value: <0.00195% CI: [26, 31.18]t-test, 2 sided
Comparison: HOMA2-B% at 52 Weeksp-value: <0.00195% CI: [24.73, 30.41]t-test, 2 sided
Comparison: HOMA2-S% at 26 Weeksp-value: 0.19495% CI: [-6.46, 1.32]t-test, 2 sided
Comparison: HOMA2-S% at 52 Weeksp-value: 0.465% CI: [-5.68, 2.27]t-test, 2 sided
Secondary
Percentage of Participants Who Achieve HbA1c ≤6.5% or <7%
Time frame: 26 weeks and 52 weeks
Population: Participants who were randomized and received at least 1 dose of study drug with evaluable HbA1c data. LOCF was used to impute missing postbaseline values.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LY2189265 + SU | Percentage of Participants Who Achieve HbA1c ≤6.5% or <7% | HbA1c ≤6.5% at Week 26 | 35.1 percentage of participants |
| LY2189265 + SU | Percentage of Participants Who Achieve HbA1c ≤6.5% or <7% | HbA1c ≤6.5% at Week 52 | 31.3 percentage of participants |
| LY2189265 + SU | Percentage of Participants Who Achieve HbA1c ≤6.5% or <7% | HbA1c <7.0% at Week 26 | 61.8 percentage of participants |
| LY2189265 + SU | Percentage of Participants Who Achieve HbA1c ≤6.5% or <7% | HbA1c <7.0% at Week 52 | 48.9 percentage of participants |
| LY2189265 + BG | Percentage of Participants Who Achieve HbA1c ≤6.5% or <7% | HbA1c ≤6.5% at Week 26 | 54.1 percentage of participants |
| LY2189265 + BG | Percentage of Participants Who Achieve HbA1c ≤6.5% or <7% | HbA1c <7.0% at Week 52 | 73.8 percentage of participants |
| LY2189265 + BG | Percentage of Participants Who Achieve HbA1c ≤6.5% or <7% | HbA1c ≤6.5% at Week 52 | 57.4 percentage of participants |
| LY2189265 + BG | Percentage of Participants Who Achieve HbA1c ≤6.5% or <7% | HbA1c <7.0% at Week 26 | 73.8 percentage of participants |
| LY2189265 + a-GI | Percentage of Participants Who Achieve HbA1c ≤6.5% or <7% | HbA1c <7.0% at Week 52 | 83.1 percentage of participants |
| LY2189265 + a-GI | Percentage of Participants Who Achieve HbA1c ≤6.5% or <7% | HbA1c ≤6.5% at Week 52 | 70.8 percentage of participants |
| LY2189265 + a-GI | Percentage of Participants Who Achieve HbA1c ≤6.5% or <7% | HbA1c <7.0% at Week 26 | 81.5 percentage of participants |
| LY2189265 + a-GI | Percentage of Participants Who Achieve HbA1c ≤6.5% or <7% | HbA1c ≤6.5% at Week 26 | 72.3 percentage of participants |
| LY2189265 + TZD | Percentage of Participants Who Achieve HbA1c ≤6.5% or <7% | HbA1c ≤6.5% at Week 26 | 60.6 percentage of participants |
| LY2189265 + TZD | Percentage of Participants Who Achieve HbA1c ≤6.5% or <7% | HbA1c ≤6.5% at Week 52 | 57.6 percentage of participants |
| LY2189265 + TZD | Percentage of Participants Who Achieve HbA1c ≤6.5% or <7% | HbA1c <7.0% at Week 52 | 77.3 percentage of participants |
| LY2189265 + TZD | Percentage of Participants Who Achieve HbA1c ≤6.5% or <7% | HbA1c <7.0% at Week 26 | 72.7 percentage of participants |
| LY2189265 + Glinides | Percentage of Participants Who Achieve HbA1c ≤6.5% or <7% | HbA1c <7.0% at Week 52 | 62.0 percentage of participants |
| LY2189265 + Glinides | Percentage of Participants Who Achieve HbA1c ≤6.5% or <7% | HbA1c <7.0% at Week 26 | 69.0 percentage of participants |
| LY2189265 + Glinides | Percentage of Participants Who Achieve HbA1c ≤6.5% or <7% | HbA1c ≤6.5% at Week 52 | 47.9 percentage of participants |
| LY2189265 + Glinides | Percentage of Participants Who Achieve HbA1c ≤6.5% or <7% | HbA1c ≤6.5% at Week 26 | 53.5 percentage of participants |