Diabetes Mellitus Type 2
Conditions
Brief summary
To study once weekly injections of LY2189265 compared to placebo on blood glucose by measuring glycosylated hemoglobin (HbA1c) change from baseline after 16 weeks in overweight Type 2 Diabetes Mellitus participants.
Interventions
DRUGLY2189265
DRUGPlacebo
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Type 2 Diabetes Mellitus \>3 months by history prior to entering the trial, based on disease diagnostic criteria from the American Diabetes Association (ADA 2007). * Men or women 18 years of age or older. Women must have a negative pregnancy test and be willing to use birth control during study duration and one month post. * Have glycosylated hemoglobin (HbA1c) of \>7.0% to ≤10.5% as determined by central laboratory at screening. * Have a body mass index (BMI) between 27 and 40 kilograms/meter squared (kg/m\^2), inclusive. * Have been on the same doses for 3 months of any approved combination of 2 oral antihyperglycemic medications in any combination of the following: sulfonylureas (e.g. Chlorpropamide or Diabinese, Glimepiride or Amaryl, Tolbutamide or Orinase, Tolazamide or Tolinase, Glipizide or Glucotrol, Glyburide also known as Micronase, Diabeta, or Glynase), biguanides (e.g. Glucophage or metformin), thiazolidinediones (e.g. Rosiglitazone or Avandia, or Pioglitazone or Actos), or dipeptidyl peptidase 4 (DPP-IV) inhibitors (e.g. Sitagliptin or Januvia). A combination pill of any 2 of these drugs is allowed (1 only), (e.g. Metformin and Glipizide or Metaglip), (e.g. Metformin and Glyburide or Glucovance), (e.g. Pioglitazone and Glimepiride or Duetact), or (e.g. Sitagliptin and Metformin or Janumet).
Exclusion criteria
* Have known Type 1 Diabetes Mellitus * Have taken glucagon-like peptide-1 (GLP-1) or any GLP-1 analog drug (Byetta) * Have a history of unstable angina, heart attack (myocardial infarction), heart arrhythmia (ventricular), congestive heart failure, or other coronary intervention (percutaneous transluminal coronary angioplasty \[PTCA\], open heart surgery, or coronary artery bypass graft \[CABG\]), a transient ischemic attack (TIA) or stroke (cerebrovascular accident) in the last 6 months prior to screening. * Have acute or chronic hepatitis or elevated liver function tests (alanine transaminase), a history of chronic or recurrent pancreatitis. Have renal disease or a serum creatinine (blood test) \>2 milligrams per deciliter (mg/dL). If taking biguanides (e.g. metformin or Glucophage), or DPP-IV inhibitors (e.g. Sitagliptin or Januvia or Janumet), creatinine must be ≤1.5 mg/dL. * Currently taking prescription or over the counter medications to prevent weight loss.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Glycosylated Hemoglobin (HbA1c) in Overweight and Obese Participants With Type 2 Diabetes Mellitus | Baseline, 16 weeks | Once weekly injections of LY2189265 (titrated and non-titrated doses) compared to placebo on blood glucose were evaluated. Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) adjusting for treatment, combination of oral medications, and baseline glycosylated hemoglobin (HbA1c). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Meal Test Glucose Excursion (Change in Blood Glucose to Test Meal) | Baseline and 16 weeks | Glucose excursion in response to a standardized solid mixed meal test was evaluated at baseline (randomization) and at Week 16, or at early termination. Each of the 2 standardized meal tests required participants to fast starting at 2200 hours the night prior to the test. A standardized breakfast meal was provided to the participant (approximately 550 kilocalorie \[Kcal\], 103 grams \[g\] carbohydrates, 22 g protein, and 8.5 g fat) and was to be consumed within 15 minutes. Serial venous blood samples were taken at the start of the meal (fasting \[0\]) and 30, 60, 90, 120, and 180 minutes after the start of the meal. Least Squares (LS) means of change in mean glucose area under the curve excursion following a test meal were calculated adjusting for treatment, combination of oral medications, and baseline. |
| Change From Baseline in Daily Mean Blood Glucose Values From the 8-point Self Monitored Blood Glucose (SMBG) Profiles | 2 separate days in the week preceding the Baseline, Week 4, Week 8, and Week 16 visits. | Change from baseline in mean daily blood glucose values were measured using self-monitored blood glucose (SMBG) data collected at the following 8 time points: pre-morning meal; 2 hours post-morning meal; pre-midday meal; 2 hours post-midday meal; pre-evening meal; 2 hours post-evening meal; bedtime; and 2:00 am. The daily mean was calculated as the average of the 8 blood glucose values collected on a particular day. Least Squares (LS) means of change from baseline of the mean of the 8 time points (Daily Mean) were calculated using analysis of covariance (ANCOVA) adjusting for treatment, combination of oral medications, and baseline. |
| Change From Baseline in Beta (β)-Cell Function and Insulin Sensitivity as Estimated by the Updated Homeostasis Model Assessment Method (HOMA2) | Baseline, 16 weeks | Homeostasis Model Assessment tool (HOMA2) of β-cell function is a technique for estimating beta-cell function (HOMA2-%B) and insulin sensitivity (HOMA2-%S) using basal serum glucose, and c-peptide concentrations. A fasting blood glucose, c-peptide, and serum insulin level were drawn for purposes of this determination just prior to the mixed meal test. |
| Percentage of Participants Achieving a Glycosylated Hemoglobin (HbA1c) of <7% or ≤6.5% | Baseline and 4 and 8 and 16 weeks | Percentages of participants who achieved glycosylated hemoglobin (HbA1c) levels of \<7% or ≤6.5% were analyzed with a logistic regression model with baseline, combination of oral medications, and treatment as factors included in the model. |
| Change From Baseline in Body Weight | Baseline, 4, 8, and 16 weeks | LS means of change from baseline were calculated using analysis of covariance (ANCOVA) adjusting for treatment, combination of oral medications, and baseline. |
| Change From Baseline in Waist Circumference | Baseline, 16 weeks | Mean change from baseline in waist circumference (a measure of central obesity). |
| Nausea and Dyspepsia Measured by Visual Analog Scale | One week before and one week after each of the Baseline and Week 4 and Week 8 and Week 16 visits | Participants were asked to score nausea and dyspepsia (abdominal pain and bloating) on a scale of 0 (none) to 100 after the largest meal of the day. |
| Change From Baseline in Fasting Blood Glucose | Baseline, 16 weeks | Fasting blood glucose is a test to determine how much glucose (sugar) is in a blood sample after an overnight fast. Least Squares (LS) means of change were calculated using analysis of covariance (ANCOVA) adjusting for treatment, combination of oral medications, and baseline. |
| Number of Participants With a Hypoglycemic Event | Baseline through 4, 8, and 16 weeks | A documented hypoglycemic episode is defined as an event which is associated with a measured blood glucose of ≤70 milligrams per deciliter (mg/dL) (3.9 millimoles per liter \[mmol/L\]), even if it was not associated with symptoms, signs, or treatment. A severe hypoglycemic episode is defined as an event with a measured blood glucose of \<50mg/dL. Participant reports of hypoglycemic events were collected at the beginning of each visit starting at Baseline. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. |
| Rate of Hypoglycemia Per 30 Days | Baseline through 16 weeks | Hypoglycemic episodes are defined as an event which is associated with reported signs and/or symptoms of hypoglycemia (for example, sweating, shakiness, tachycardia, etc.) or a documented blood glucose (BG) concentration of ≤70 milligrams per deciliter (mg/dL) (3.9 millimoles per liter \[mmol/L\]), even if it was not associated with symptoms, signs, or treatment. The rate is the average number of days out of 30 that a participant reported hypoglycemia. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. |
| Change From Baseline in Lipids | Baseline, 16 weeks | Lipids include total cholesterol, low-density lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL)-cholesterol, and triglycerides. |
| Participants Perception of Medication Effectiveness Using the Perceptions About Medications - Diabetes, Short Version (PAM-D-S) Questionnaire | Baseline and 4 and 8 and 16 weeks | The Perceptions about Medications - Diabetes, Short Version (PAM-D-S) questionnaire consisted of: 2 items in which respondents were asked about their satisfaction with their diabetes medication over the past week using a 6-point scale ranging from 1 completely dissatisfied to 6 completely satisfied; 10 items in which respondents were asked about the effectiveness of their diabetes medications in the past week using a 4-point scale ranging from 1 all of the time to 4 none of the time; and 15 items asking respondents to indicate the frequency of physical side effects in the past week using a 4-point scale ranging from 1 all of the time to 4 none of the time. These items were exploratory items taken from a Diabetes Medicines Survey and had not been validated as a scale. The percentage of participants that rated their general health as good or better are summarized. |
| Validation of the Psychometric Properties of the Perceptions About Medications - Diabetes, Short Version (PAM-D-S) Questionnaire | Baseline and 4 and 8 and 16 weeks | This purpose of this outcome measure was to validate the PAM-D-S questionnaire for future use. Please refer to Outcome Measure #14 for a description of the PAM-D-S questionnaire and results collected. A preliminary analysis indicated modifications to the questionnaire were required and further study is necessary to complete the validation. Therefore, the PAM-D-S questionnaire was not validated as a part of Study H9X-MC-GBCJ. |
| Pharmacokinetics (PK) of LY2189265 - Area Under the Concentration Time Curve (AUC) | Time zero to 168 hours after study drug administration at 4, 8, and 16 weeks | The population mean estimates and standard deviations were calculated for pharmacokinetic parameters (area under the concentration time curve \[AUC\] at steady state from time zero to 168 hours after study drug administration). |
| Change From Baseline in Gastroparesis Cardinal Symptom Index (GCSI) Scores | Baseline and 4 and 8 and 16 weeks | Gastroparesis Cardinal Symptom Index (GCSI) is a participant-completed questionnaire designed to assess the severity of symptoms consistent with delayed gastric emptying (nausea/vomiting, abdominal bloating, and stomach fullness) at each study visit. GCSI scores ranged from 0=none, 1=very mild, 2=mild, 3=moderate, 4=severe, to 5=very severe. |
Countries
Puerto Rico, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 1.0/2.0 Milligram (mg) LY2189265 LY2189265: 1.0 milligram (mg), subcutaneous (SC) injection, once weekly (QW) for 4 weeks; followed by 2.0 mg, SC injection, QW for 12 weeks | 65 |
| 1.0/1.0 Milligram (mg) LY2189265 LY2189265: 1.0 milligram (mg), subcutaneous (SC) injection, once weekly (QW) for 16 weeks | 65 |
| 0.5/1.0 Milligram (mg) LY2189265 LY2189265: 0.5 milligram (mg), subcutaneous (SC) injection, once weekly (QW) for 4 weeks; followed by 1.0 mg, SC injection, QW for 12 weeks | 66 |
| Placebo Placebo: subcutaneous (SC), once weekly (QW) for 16 weeks | 66 |
| Total | 262 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 4 | 4 | 3 | 1 |
| Overall Study | Entry Criteria Not Met | 1 | 0 | 2 | 1 |
| Overall Study | Lost to Follow-up | 1 | 1 | 1 | 1 |
| Overall Study | Physician Decision | 1 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 2 | 2 | 3 |
Baseline characteristics
| Characteristic | 1.0/1.0 Milligram (mg) LY2189265 | Total | Placebo | 0.5/1.0 Milligram (mg) LY2189265 | 1.0/2.0 Milligram (mg) LY2189265 |
|---|---|---|---|---|---|
| Age, Continuous | 57.46 years STANDARD_DEVIATION 11.72 | 56.65 years STANDARD_DEVIATION 11.84 | 55.96 years STANDARD_DEVIATION 12.49 | 58.65 years STANDARD_DEVIATION 11.69 | 54.49 years STANDARD_DEVIATION 11.28 |
| Body Mass Index (BMI) | 33.85 kilograms per square meters (kg/m^2) STANDARD_DEVIATION 3.95 | 33.92 kilograms per square meters (kg/m^2) STANDARD_DEVIATION 4.1 | 33.89 kilograms per square meters (kg/m^2) STANDARD_DEVIATION 4.31 | 33.70 kilograms per square meters (kg/m^2) STANDARD_DEVIATION 4.11 | 34.24 kilograms per square meters (kg/m^2) STANDARD_DEVIATION 4.11 |
| Body Weight | 96.68 kilograms (kg) STANDARD_DEVIATION 16.51 | 96.18 kilograms (kg) STANDARD_DEVIATION 16.68 | 94.74 kilograms (kg) STANDARD_DEVIATION 15.21 | 94.76 kilograms (kg) STANDARD_DEVIATION 16.53 | 98.60 kilograms (kg) STANDARD_DEVIATION 18.41 |
| Duration of Diabetes | 8.13 years STANDARD_DEVIATION 5.43 | 8.30 years STANDARD_DEVIATION 6.41 | 7.48 years STANDARD_DEVIATION 5.41 | 8.97 years STANDARD_DEVIATION 7.62 | 8.63 years STANDARD_DEVIATION 6.92 |
| Glycosylated Hemoglobin (HbA1c) | 8.25 percentage of glycosylated hemoglobin STANDARD_DEVIATION 0.99 | 8.24 percentage of glycosylated hemoglobin STANDARD_DEVIATION 0.93 | 8.05 percentage of glycosylated hemoglobin STANDARD_DEVIATION 0.82 | 8.25 percentage of glycosylated hemoglobin STANDARD_DEVIATION 0.89 | 8.43 percentage of glycosylated hemoglobin STANDARD_DEVIATION 0.99 |
| Race/Ethnicity, Customized African | 6 participants | 19 participants | 4 participants | 5 participants | 4 participants |
| Race/Ethnicity, Customized Caucasian | 39 participants | 151 participants | 36 participants | 40 participants | 36 participants |
| Race/Ethnicity, Customized East Asian | 0 participants | 1 participants | 0 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Hispanic | 20 participants | 88 participants | 26 participants | 19 participants | 23 participants |
| Race/Ethnicity, Customized Native American | 0 participants | 3 participants | 0 participants | 2 participants | 1 participants |
| Region of Enrollment Puerto Rico | 9 participants | 35 participants | 8 participants | 9 participants | 9 participants |
| Region of Enrollment United States | 56 participants | 227 participants | 58 participants | 57 participants | 56 participants |
| Sex: Female, Male Female | 30 Participants | 129 Participants | 37 Participants | 31 Participants | 31 Participants |
| Sex: Female, Male Male | 35 Participants | 133 Participants | 29 Participants | 35 Participants | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 41 / 65 | 35 / 65 | 40 / 66 | 36 / 66 |
| serious Total, serious adverse events | 1 / 65 | 2 / 65 | 3 / 66 | 1 / 66 |
Outcome results
Primary
Change From Baseline in Glycosylated Hemoglobin (HbA1c) in Overweight and Obese Participants With Type 2 Diabetes Mellitus
Once weekly injections of LY2189265 (titrated and non-titrated doses) compared to placebo on blood glucose were evaluated. Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) adjusting for treatment, combination of oral medications, and baseline glycosylated hemoglobin (HbA1c).
Time frame: Baseline, 16 weeks
Population: Participants who received at least one dose of LY2189265 or Placebo with evaluable glycosylated hemoglobin (HbA1c) data. Last observation carried forward (LOCF) was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 1.0/2.0 Milligram (mg) LY2189265 | Change From Baseline in Glycosylated Hemoglobin (HbA1c) in Overweight and Obese Participants With Type 2 Diabetes Mellitus | -1.52 percentage of glycosylated hemoglobin | Standard Error 0.12 |
| 1.0/1.0 Milligram (mg) LY2189265 | Change From Baseline in Glycosylated Hemoglobin (HbA1c) in Overweight and Obese Participants With Type 2 Diabetes Mellitus | -1.29 percentage of glycosylated hemoglobin | Standard Error 0.12 |
| 0.5/1.0 Milligram (mg) LY2189265 | Change From Baseline in Glycosylated Hemoglobin (HbA1c) in Overweight and Obese Participants With Type 2 Diabetes Mellitus | -1.28 percentage of glycosylated hemoglobin | Standard Error 0.12 |
| Placebo | Change From Baseline in Glycosylated Hemoglobin (HbA1c) in Overweight and Obese Participants With Type 2 Diabetes Mellitus | -0.27 percentage of glycosylated hemoglobin | Standard Error 0.12 |
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
Secondary
Change From Baseline in Beta (β)-Cell Function and Insulin Sensitivity as Estimated by the Updated Homeostasis Model Assessment Method (HOMA2)
Homeostasis Model Assessment tool (HOMA2) of β-cell function is a technique for estimating beta-cell function (HOMA2-%B) and insulin sensitivity (HOMA2-%S) using basal serum glucose, and c-peptide concentrations. A fasting blood glucose, c-peptide, and serum insulin level were drawn for purposes of this determination just prior to the mixed meal test.
Time frame: Baseline, 16 weeks
Population: Participants who received at least one dose of LY2189265 or Placebo with evaluable HOMA2-%B or HOMA2-%S data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1.0/2.0 Milligram (mg) LY2189265 | Change From Baseline in Beta (β)-Cell Function and Insulin Sensitivity as Estimated by the Updated Homeostasis Model Assessment Method (HOMA2) | HOMA2-%S | 3.58 percentage of HOMA2 | Standard Deviation 18.51 |
| 1.0/2.0 Milligram (mg) LY2189265 | Change From Baseline in Beta (β)-Cell Function and Insulin Sensitivity as Estimated by the Updated Homeostasis Model Assessment Method (HOMA2) | HOMA2-%B | 45.61 percentage of HOMA2 | Standard Deviation 55.2 |
| 1.0/1.0 Milligram (mg) LY2189265 | Change From Baseline in Beta (β)-Cell Function and Insulin Sensitivity as Estimated by the Updated Homeostasis Model Assessment Method (HOMA2) | HOMA2-%B | 44.26 percentage of HOMA2 | Standard Deviation 93.89 |
| 1.0/1.0 Milligram (mg) LY2189265 | Change From Baseline in Beta (β)-Cell Function and Insulin Sensitivity as Estimated by the Updated Homeostasis Model Assessment Method (HOMA2) | HOMA2-%S | -1.65 percentage of HOMA2 | Standard Deviation 17.19 |
| 0.5/1.0 Milligram (mg) LY2189265 | Change From Baseline in Beta (β)-Cell Function and Insulin Sensitivity as Estimated by the Updated Homeostasis Model Assessment Method (HOMA2) | HOMA2-%S | 0.46 percentage of HOMA2 | Standard Deviation 13.78 |
| 0.5/1.0 Milligram (mg) LY2189265 | Change From Baseline in Beta (β)-Cell Function and Insulin Sensitivity as Estimated by the Updated Homeostasis Model Assessment Method (HOMA2) | HOMA2-%B | 39.20 percentage of HOMA2 | Standard Deviation 45.56 |
| Placebo | Change From Baseline in Beta (β)-Cell Function and Insulin Sensitivity as Estimated by the Updated Homeostasis Model Assessment Method (HOMA2) | HOMA2-%S | 2.46 percentage of HOMA2 | Standard Deviation 12.23 |
| Placebo | Change From Baseline in Beta (β)-Cell Function and Insulin Sensitivity as Estimated by the Updated Homeostasis Model Assessment Method (HOMA2) | HOMA2-%B | 1.04 percentage of HOMA2 | Standard Deviation 41.12 |
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: 0.004ANCOVA
p-value: 0.904ANCOVA
p-value: 0.138ANCOVA
p-value: 0.729ANCOVA
Secondary
Change From Baseline in Body Weight
LS means of change from baseline were calculated using analysis of covariance (ANCOVA) adjusting for treatment, combination of oral medications, and baseline.
Time frame: Baseline, 4, 8, and 16 weeks
Population: Participants who received at least one dose of LY2189265 or Placebo with evaluable body weight data. For Week 16 data, last observation carried forward (LOCF) was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 1.0/2.0 Milligram (mg) LY2189265 | Change From Baseline in Body Weight | 4 weeks (n=63, n=63, n=65, n=65) | -1.28 kilograms (kg) | Standard Error 0.23 |
| 1.0/2.0 Milligram (mg) LY2189265 | Change From Baseline in Body Weight | 16 weeks (n=63, n=63, n=65, n=65) | -2.51 kilograms (kg) | Standard Error 0.38 |
| 1.0/2.0 Milligram (mg) LY2189265 | Change From Baseline in Body Weight | 8 weeks (n=61, n=60, n=63, n=64) | -2.12 kilograms (kg) | Standard Error 0.31 |
| 1.0/1.0 Milligram (mg) LY2189265 | Change From Baseline in Body Weight | 4 weeks (n=63, n=63, n=65, n=65) | -1.08 kilograms (kg) | Standard Error 0.23 |
| 1.0/1.0 Milligram (mg) LY2189265 | Change From Baseline in Body Weight | 16 weeks (n=63, n=63, n=65, n=65) | -1.40 kilograms (kg) | Standard Error 0.38 |
| 1.0/1.0 Milligram (mg) LY2189265 | Change From Baseline in Body Weight | 8 weeks (n=61, n=60, n=63, n=64) | -1.67 kilograms (kg) | Standard Error 0.32 |
| 0.5/1.0 Milligram (mg) LY2189265 | Change From Baseline in Body Weight | 8 weeks (n=61, n=60, n=63, n=64) | -1.39 kilograms (kg) | Standard Error 0.31 |
| 0.5/1.0 Milligram (mg) LY2189265 | Change From Baseline in Body Weight | 4 weeks (n=63, n=63, n=65, n=65) | -0.50 kilograms (kg) | Standard Error 0.22 |
| 0.5/1.0 Milligram (mg) LY2189265 | Change From Baseline in Body Weight | 16 weeks (n=63, n=63, n=65, n=65) | -1.58 kilograms (kg) | Standard Error 0.37 |
| Placebo | Change From Baseline in Body Weight | 4 weeks (n=63, n=63, n=65, n=65) | -0.06 kilograms (kg) | Standard Error 0.22 |
| Placebo | Change From Baseline in Body Weight | 16 weeks (n=63, n=63, n=65, n=65) | -0.07 kilograms (kg) | Standard Error 0.38 |
| Placebo | Change From Baseline in Body Weight | 8 weeks (n=61, n=60, n=63, n=64) | -0.12 kilograms (kg) | Standard Error 0.31 |
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: 0.113ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: 0.004ANCOVA
p-value: 0.001ANCOVA
Secondary
Change From Baseline in Daily Mean Blood Glucose Values From the 8-point Self Monitored Blood Glucose (SMBG) Profiles
Change from baseline in mean daily blood glucose values were measured using self-monitored blood glucose (SMBG) data collected at the following 8 time points: pre-morning meal; 2 hours post-morning meal; pre-midday meal; 2 hours post-midday meal; pre-evening meal; 2 hours post-evening meal; bedtime; and 2:00 am. The daily mean was calculated as the average of the 8 blood glucose values collected on a particular day. Least Squares (LS) means of change from baseline of the mean of the 8 time points (Daily Mean) were calculated using analysis of covariance (ANCOVA) adjusting for treatment, combination of oral medications, and baseline.
Time frame: 2 separate days in the week preceding the Baseline, Week 4, Week 8, and Week 16 visits.
Population: Participants who received at least one dose of LY2189265 or Placebo with evaluable blood glucose (SMBG) data. For Week 16 data, last observation carried forward (LOCF) was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 1.0/2.0 Milligram (mg) LY2189265 | Change From Baseline in Daily Mean Blood Glucose Values From the 8-point Self Monitored Blood Glucose (SMBG) Profiles | Week 4 (n=34, n=38, n=35, n=41) | -31.19 milligrams per deciliter (mg/dL) | Standard Error 5.85 |
| 1.0/2.0 Milligram (mg) LY2189265 | Change From Baseline in Daily Mean Blood Glucose Values From the 8-point Self Monitored Blood Glucose (SMBG) Profiles | Week 16 (n=41, n=50, n=46, n=49) | -37.49 milligrams per deciliter (mg/dL) | Standard Error 5.89 |
| 1.0/2.0 Milligram (mg) LY2189265 | Change From Baseline in Daily Mean Blood Glucose Values From the 8-point Self Monitored Blood Glucose (SMBG) Profiles | Week 8 (n=34, n=41, n=38, n=41) | -43.00 milligrams per deciliter (mg/dL) | Standard Error 5.88 |
| 1.0/1.0 Milligram (mg) LY2189265 | Change From Baseline in Daily Mean Blood Glucose Values From the 8-point Self Monitored Blood Glucose (SMBG) Profiles | Week 4 (n=34, n=38, n=35, n=41) | -35.94 milligrams per deciliter (mg/dL) | Standard Error 5.3 |
| 1.0/1.0 Milligram (mg) LY2189265 | Change From Baseline in Daily Mean Blood Glucose Values From the 8-point Self Monitored Blood Glucose (SMBG) Profiles | Week 16 (n=41, n=50, n=46, n=49) | -41.79 milligrams per deciliter (mg/dL) | Standard Error 5.25 |
| 1.0/1.0 Milligram (mg) LY2189265 | Change From Baseline in Daily Mean Blood Glucose Values From the 8-point Self Monitored Blood Glucose (SMBG) Profiles | Week 8 (n=34, n=41, n=38, n=41) | -40.68 milligrams per deciliter (mg/dL) | Standard Error 5.43 |
| 0.5/1.0 Milligram (mg) LY2189265 | Change From Baseline in Daily Mean Blood Glucose Values From the 8-point Self Monitored Blood Glucose (SMBG) Profiles | Week 8 (n=34, n=41, n=38, n=41) | -36.02 milligrams per deciliter (mg/dL) | Standard Error 5.35 |
| 0.5/1.0 Milligram (mg) LY2189265 | Change From Baseline in Daily Mean Blood Glucose Values From the 8-point Self Monitored Blood Glucose (SMBG) Profiles | Week 4 (n=34, n=38, n=35, n=41) | -31.66 milligrams per deciliter (mg/dL) | Standard Error 5.36 |
| 0.5/1.0 Milligram (mg) LY2189265 | Change From Baseline in Daily Mean Blood Glucose Values From the 8-point Self Monitored Blood Glucose (SMBG) Profiles | Week 16 (n=41, n=50, n=46, n=49) | -32.52 milligrams per deciliter (mg/dL) | Standard Error 5.4 |
| Placebo | Change From Baseline in Daily Mean Blood Glucose Values From the 8-point Self Monitored Blood Glucose (SMBG) Profiles | Week 4 (n=34, n=38, n=35, n=41) | -8.10 milligrams per deciliter (mg/dL) | Standard Error 5.06 |
| Placebo | Change From Baseline in Daily Mean Blood Glucose Values From the 8-point Self Monitored Blood Glucose (SMBG) Profiles | Week 16 (n=41, n=50, n=46, n=49) | -8.67 milligrams per deciliter (mg/dL) | Standard Error 5.3 |
| Placebo | Change From Baseline in Daily Mean Blood Glucose Values From the 8-point Self Monitored Blood Glucose (SMBG) Profiles | Week 8 (n=34, n=41, n=38, n=41) | -14.58 milligrams per deciliter (mg/dL) | Standard Error 5.38 |
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
Secondary
Change From Baseline in Fasting Blood Glucose
Fasting blood glucose is a test to determine how much glucose (sugar) is in a blood sample after an overnight fast. Least Squares (LS) means of change were calculated using analysis of covariance (ANCOVA) adjusting for treatment, combination of oral medications, and baseline.
Time frame: Baseline, 16 weeks
Population: Participants who received at least one dose of LY2189265 or Placebo with evaluable fasting blood glucose data. Last observation carried forward (LOCF) was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 1.0/2.0 Milligram (mg) LY2189265 | Change From Baseline in Fasting Blood Glucose | -2.64 millimoles per liter (mmol/L) | Standard Error 0.33 |
| 1.0/1.0 Milligram (mg) LY2189265 | Change From Baseline in Fasting Blood Glucose | -2.04 millimoles per liter (mmol/L) | Standard Error 0.34 |
| 0.5/1.0 Milligram (mg) LY2189265 | Change From Baseline in Fasting Blood Glucose | -2.09 millimoles per liter (mmol/L) | Standard Error 0.34 |
| Placebo | Change From Baseline in Fasting Blood Glucose | -0.49 millimoles per liter (mmol/L) | Standard Error 0.32 |
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
Secondary
Change From Baseline in Gastroparesis Cardinal Symptom Index (GCSI) Scores
Gastroparesis Cardinal Symptom Index (GCSI) is a participant-completed questionnaire designed to assess the severity of symptoms consistent with delayed gastric emptying (nausea/vomiting, abdominal bloating, and stomach fullness) at each study visit. GCSI scores ranged from 0=none, 1=very mild, 2=mild, 3=moderate, 4=severe, to 5=very severe.
Time frame: Baseline and 4 and 8 and 16 weeks
Population: Participants who received at least one dose of LY2189265 or Placebo with evaluable Gastroparesis Cardinal Symptom Index (GCSI) questionnaire data. For Week 16 data, last observation carried forward (LOCF) was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1.0/2.0 Milligram (mg) LY2189265 | Change From Baseline in Gastroparesis Cardinal Symptom Index (GCSI) Scores | Bloating, Week 8 (n=59, n=60, n=60, n=63) | 0.41 units on a scale | Standard Deviation 1.34 |
| 1.0/2.0 Milligram (mg) LY2189265 | Change From Baseline in Gastroparesis Cardinal Symptom Index (GCSI) Scores | Stomach fullness, Week 4 (n=62, n=60, n=65, n=65) | 0.55 units on a scale | Standard Deviation 1.51 |
| 1.0/2.0 Milligram (mg) LY2189265 | Change From Baseline in Gastroparesis Cardinal Symptom Index (GCSI) Scores | Stomach fullness, Week 16 (n=63, n=62, n=65, n=65) | 0.21 units on a scale | Standard Deviation 1.58 |
| 1.0/2.0 Milligram (mg) LY2189265 | Change From Baseline in Gastroparesis Cardinal Symptom Index (GCSI) Scores | Stomach fullness, Week 8 (n=59, n=60, n=59, n=63) | 0.46 units on a scale | Standard Deviation 1.65 |
| 1.0/2.0 Milligram (mg) LY2189265 | Change From Baseline in Gastroparesis Cardinal Symptom Index (GCSI) Scores | Bloating, Week 4 (n=62, n=60, n=65, n=65) | 0.35 units on a scale | Standard Deviation 0.1 |
| 1.0/2.0 Milligram (mg) LY2189265 | Change From Baseline in Gastroparesis Cardinal Symptom Index (GCSI) Scores | Nausea/Vomiting, Week 16 (n=63, n=62, n=65, n=65) | 0.20 units on a scale | Standard Deviation 0.64 |
| 1.0/2.0 Milligram (mg) LY2189265 | Change From Baseline in Gastroparesis Cardinal Symptom Index (GCSI) Scores | Bloating, Week 16 (n=63, n=62, n=65, n=65) | 0.02 units on a scale | Standard Deviation 1.04 |
| 1.0/2.0 Milligram (mg) LY2189265 | Change From Baseline in Gastroparesis Cardinal Symptom Index (GCSI) Scores | Nausea/Vomiting, Week 8 (n=59, n=60, n=60, n=63) | 0.46 units on a scale | Standard Deviation 0.97 |
| 1.0/2.0 Milligram (mg) LY2189265 | Change From Baseline in Gastroparesis Cardinal Symptom Index (GCSI) Scores | Nausea/Vomiting, Week 4 (n=62, n=60, n=64, n=65) | 0.25 units on a scale | Standard Deviation 0.71 |
| 1.0/1.0 Milligram (mg) LY2189265 | Change From Baseline in Gastroparesis Cardinal Symptom Index (GCSI) Scores | Nausea/Vomiting, Week 4 (n=62, n=60, n=64, n=65) | 0.19 units on a scale | Standard Deviation 0.71 |
| 1.0/1.0 Milligram (mg) LY2189265 | Change From Baseline in Gastroparesis Cardinal Symptom Index (GCSI) Scores | Nausea/Vomiting, Week 8 (n=59, n=60, n=60, n=63) | 0.04 units on a scale | Standard Deviation 0.64 |
| 1.0/1.0 Milligram (mg) LY2189265 | Change From Baseline in Gastroparesis Cardinal Symptom Index (GCSI) Scores | Stomach fullness, Week 8 (n=59, n=60, n=59, n=63) | 0.30 units on a scale | Standard Deviation 1.33 |
| 1.0/1.0 Milligram (mg) LY2189265 | Change From Baseline in Gastroparesis Cardinal Symptom Index (GCSI) Scores | Nausea/Vomiting, Week 16 (n=63, n=62, n=65, n=65) | -0.01 units on a scale | Standard Deviation 0.59 |
| 1.0/1.0 Milligram (mg) LY2189265 | Change From Baseline in Gastroparesis Cardinal Symptom Index (GCSI) Scores | Stomach fullness, Week 16 (n=63, n=62, n=65, n=65) | 0.27 units on a scale | Standard Deviation 1.28 |
| 1.0/1.0 Milligram (mg) LY2189265 | Change From Baseline in Gastroparesis Cardinal Symptom Index (GCSI) Scores | Stomach fullness, Week 4 (n=62, n=60, n=65, n=65) | 0.57 units on a scale | Standard Deviation 1.35 |
| 1.0/1.0 Milligram (mg) LY2189265 | Change From Baseline in Gastroparesis Cardinal Symptom Index (GCSI) Scores | Bloating, Week 4 (n=62, n=60, n=65, n=65) | 0.28 units on a scale | Standard Deviation 0.93 |
| 1.0/1.0 Milligram (mg) LY2189265 | Change From Baseline in Gastroparesis Cardinal Symptom Index (GCSI) Scores | Bloating, Week 8 (n=59, n=60, n=60, n=63) | 0.13 units on a scale | Standard Deviation 1.02 |
| 1.0/1.0 Milligram (mg) LY2189265 | Change From Baseline in Gastroparesis Cardinal Symptom Index (GCSI) Scores | Bloating, Week 16 (n=63, n=62, n=65, n=65) | 0.11 units on a scale | Standard Deviation 0.94 |
| 0.5/1.0 Milligram (mg) LY2189265 | Change From Baseline in Gastroparesis Cardinal Symptom Index (GCSI) Scores | Stomach fullness, Week 4 (n=62, n=60, n=65, n=65) | 0.62 units on a scale | Standard Deviation 1.26 |
| 0.5/1.0 Milligram (mg) LY2189265 | Change From Baseline in Gastroparesis Cardinal Symptom Index (GCSI) Scores | Stomach fullness, Week 8 (n=59, n=60, n=59, n=63) | 0.71 units on a scale | Standard Deviation 1.54 |
| 0.5/1.0 Milligram (mg) LY2189265 | Change From Baseline in Gastroparesis Cardinal Symptom Index (GCSI) Scores | Bloating, Week 16 (n=63, n=62, n=65, n=65) | 0.32 units on a scale | Standard Deviation 1.32 |
| 0.5/1.0 Milligram (mg) LY2189265 | Change From Baseline in Gastroparesis Cardinal Symptom Index (GCSI) Scores | Bloating, Week 8 (n=59, n=60, n=60, n=63) | 0.14 units on a scale | Standard Deviation 1.32 |
| 0.5/1.0 Milligram (mg) LY2189265 | Change From Baseline in Gastroparesis Cardinal Symptom Index (GCSI) Scores | Nausea/Vomiting, Week 16 (n=63, n=62, n=65, n=65) | 0.27 units on a scale | Standard Deviation 0.48 |
| 0.5/1.0 Milligram (mg) LY2189265 | Change From Baseline in Gastroparesis Cardinal Symptom Index (GCSI) Scores | Nausea/Vomiting, Week 8 (n=59, n=60, n=60, n=63) | 0.28 units on a scale | Standard Deviation 0.62 |
| 0.5/1.0 Milligram (mg) LY2189265 | Change From Baseline in Gastroparesis Cardinal Symptom Index (GCSI) Scores | Stomach fullness, Week 16 (n=63, n=62, n=65, n=65) | 0.51 units on a scale | Standard Deviation 1.34 |
| 0.5/1.0 Milligram (mg) LY2189265 | Change From Baseline in Gastroparesis Cardinal Symptom Index (GCSI) Scores | Nausea/Vomiting, Week 4 (n=62, n=60, n=64, n=65) | 0.22 units on a scale | Standard Deviation 0.52 |
| 0.5/1.0 Milligram (mg) LY2189265 | Change From Baseline in Gastroparesis Cardinal Symptom Index (GCSI) Scores | Bloating, Week 4 (n=62, n=60, n=65, n=65) | 0.19 units on a scale | Standard Deviation 0.91 |
| Placebo | Change From Baseline in Gastroparesis Cardinal Symptom Index (GCSI) Scores | Nausea/Vomiting, Week 16 (n=63, n=62, n=65, n=65) | -0.01 units on a scale | Standard Deviation 0.36 |
| Placebo | Change From Baseline in Gastroparesis Cardinal Symptom Index (GCSI) Scores | Nausea/Vomiting, Week 4 (n=62, n=60, n=64, n=65) | 0.03 units on a scale | Standard Deviation 0.4 |
| Placebo | Change From Baseline in Gastroparesis Cardinal Symptom Index (GCSI) Scores | Stomach fullness, Week 4 (n=62, n=60, n=65, n=65) | 0.35 units on a scale | Standard Deviation 1.39 |
| Placebo | Change From Baseline in Gastroparesis Cardinal Symptom Index (GCSI) Scores | Stomach fullness, Week 8 (n=59, n=60, n=59, n=63) | 0.25 units on a scale | Standard Deviation 1.39 |
| Placebo | Change From Baseline in Gastroparesis Cardinal Symptom Index (GCSI) Scores | Stomach fullness, Week 16 (n=63, n=62, n=65, n=65) | 0.15 units on a scale | Standard Deviation 1.34 |
| Placebo | Change From Baseline in Gastroparesis Cardinal Symptom Index (GCSI) Scores | Bloating, Week 4 (n=62, n=60, n=65, n=65) | 0.28 units on a scale | Standard Deviation 0.84 |
| Placebo | Change From Baseline in Gastroparesis Cardinal Symptom Index (GCSI) Scores | Bloating, Week 8 (n=59, n=60, n=60, n=63) | 0.18 units on a scale | Standard Deviation 0.92 |
| Placebo | Change From Baseline in Gastroparesis Cardinal Symptom Index (GCSI) Scores | Bloating, Week 16 (n=63, n=62, n=65, n=65) | 0.28 units on a scale | Standard Deviation 0.86 |
| Placebo | Change From Baseline in Gastroparesis Cardinal Symptom Index (GCSI) Scores | Nausea/Vomiting, Week 8 (n=59, n=60, n=60, n=63) | 0.02 units on a scale | Standard Deviation 0.39 |
Secondary
Change From Baseline in Lipids
Lipids include total cholesterol, low-density lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL)-cholesterol, and triglycerides.
Time frame: Baseline, 16 weeks
Population: Participants who received at least one dose of LY2189265 or Placebo with evaluable lipid data. Last observation carried forward (LOCF) was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| 1.0/2.0 Milligram (mg) LY2189265 | Change From Baseline in Lipids | Cholesterol (n=61, n=60, n=60, n=62) | -0.34 millimoles per liter (mmol/L) |
| 1.0/2.0 Milligram (mg) LY2189265 | Change From Baseline in Lipids | LDL-Cholesterol (n=61, n=60, n=60, n=61) | -0.26 millimoles per liter (mmol/L) |
| 1.0/2.0 Milligram (mg) LY2189265 | Change From Baseline in Lipids | HDL-Cholesterol (n=61, n=60, n=60, n=61) | -0.02 millimoles per liter (mmol/L) |
| 1.0/2.0 Milligram (mg) LY2189265 | Change From Baseline in Lipids | Triglycerides (n=61, n=60, n=60, n=61) | -0.16 millimoles per liter (mmol/L) |
| 1.0/1.0 Milligram (mg) LY2189265 | Change From Baseline in Lipids | Triglycerides (n=61, n=60, n=60, n=61) | -0.02 millimoles per liter (mmol/L) |
| 1.0/1.0 Milligram (mg) LY2189265 | Change From Baseline in Lipids | HDL-Cholesterol (n=61, n=60, n=60, n=61) | -0.02 millimoles per liter (mmol/L) |
| 1.0/1.0 Milligram (mg) LY2189265 | Change From Baseline in Lipids | LDL-Cholesterol (n=61, n=60, n=60, n=61) | -0.09 millimoles per liter (mmol/L) |
| 1.0/1.0 Milligram (mg) LY2189265 | Change From Baseline in Lipids | Cholesterol (n=61, n=60, n=60, n=62) | -0.05 millimoles per liter (mmol/L) |
| 0.5/1.0 Milligram (mg) LY2189265 | Change From Baseline in Lipids | HDL-Cholesterol (n=61, n=60, n=60, n=61) | 0.00 millimoles per liter (mmol/L) |
| 0.5/1.0 Milligram (mg) LY2189265 | Change From Baseline in Lipids | Triglycerides (n=61, n=60, n=60, n=61) | -0.16 millimoles per liter (mmol/L) |
| 0.5/1.0 Milligram (mg) LY2189265 | Change From Baseline in Lipids | LDL-Cholesterol (n=61, n=60, n=60, n=61) | -0.07 millimoles per liter (mmol/L) |
| 0.5/1.0 Milligram (mg) LY2189265 | Change From Baseline in Lipids | Cholesterol (n=61, n=60, n=60, n=62) | -0.09 millimoles per liter (mmol/L) |
| Placebo | Change From Baseline in Lipids | LDL-Cholesterol (n=61, n=60, n=60, n=61) | 0.10 millimoles per liter (mmol/L) |
| Placebo | Change From Baseline in Lipids | Cholesterol (n=61, n=60, n=60, n=62) | 0.18 millimoles per liter (mmol/L) |
| Placebo | Change From Baseline in Lipids | Triglycerides (n=61, n=60, n=60, n=61) | 0.00 millimoles per liter (mmol/L) |
| Placebo | Change From Baseline in Lipids | HDL-Cholesterol (n=61, n=60, n=60, n=61) | 0.00 millimoles per liter (mmol/L) |
Secondary
Change From Baseline in Waist Circumference
Mean change from baseline in waist circumference (a measure of central obesity).
Time frame: Baseline, 16 weeks
Population: Participants who received at least one dose of LY2189265 or Placebo with evaluable waist circumference data. For Week 16 data, last observation carried forward (LOCF) was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 1.0/2.0 Milligram (mg) LY2189265 | Change From Baseline in Waist Circumference | -1.92 centimeters (cm) | Standard Deviation 4.24 |
| 1.0/1.0 Milligram (mg) LY2189265 | Change From Baseline in Waist Circumference | -1.51 centimeters (cm) | Standard Deviation 4.56 |
| 0.5/1.0 Milligram (mg) LY2189265 | Change From Baseline in Waist Circumference | -1.33 centimeters (cm) | Standard Deviation 4.21 |
| Placebo | Change From Baseline in Waist Circumference | 0.20 centimeters (cm) | Standard Deviation 3.4 |
p-value: 0.009ANCOVA
p-value: 0.028ANCOVA
p-value: 0.047ANCOVA
Secondary
Meal Test Glucose Excursion (Change in Blood Glucose to Test Meal)
Glucose excursion in response to a standardized solid mixed meal test was evaluated at baseline (randomization) and at Week 16, or at early termination. Each of the 2 standardized meal tests required participants to fast starting at 2200 hours the night prior to the test. A standardized breakfast meal was provided to the participant (approximately 550 kilocalorie \[Kcal\], 103 grams \[g\] carbohydrates, 22 g protein, and 8.5 g fat) and was to be consumed within 15 minutes. Serial venous blood samples were taken at the start of the meal (fasting \[0\]) and 30, 60, 90, 120, and 180 minutes after the start of the meal. Least Squares (LS) means of change in mean glucose area under the curve excursion following a test meal were calculated adjusting for treatment, combination of oral medications, and baseline.
Time frame: Baseline and 16 weeks
Population: Participants who received at least one dose of LY2189265 or Placebo with evaluable glucose excursion data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1.0/2.0 Milligram (mg) LY2189265 | Meal Test Glucose Excursion (Change in Blood Glucose to Test Meal) | Baseline (n=63, n=62, n=66, n=63) | 11.03 millimoles per liter (mmol/L)*minute | Standard Deviation 5.02 |
| 1.0/2.0 Milligram (mg) LY2189265 | Meal Test Glucose Excursion (Change in Blood Glucose to Test Meal) | Week 16 (n=52, n=56, n=54, n=59) | 8.16 millimoles per liter (mmol/L)*minute | Standard Deviation 4.58 |
| 1.0/1.0 Milligram (mg) LY2189265 | Meal Test Glucose Excursion (Change in Blood Glucose to Test Meal) | Week 16 (n=52, n=56, n=54, n=59) | 9.92 millimoles per liter (mmol/L)*minute | Standard Deviation 5.32 |
| 1.0/1.0 Milligram (mg) LY2189265 | Meal Test Glucose Excursion (Change in Blood Glucose to Test Meal) | Baseline (n=63, n=62, n=66, n=63) | 11.12 millimoles per liter (mmol/L)*minute | Standard Deviation 4.77 |
| 0.5/1.0 Milligram (mg) LY2189265 | Meal Test Glucose Excursion (Change in Blood Glucose to Test Meal) | Baseline (n=63, n=62, n=66, n=63) | 10.32 millimoles per liter (mmol/L)*minute | Standard Deviation 4.93 |
| 0.5/1.0 Milligram (mg) LY2189265 | Meal Test Glucose Excursion (Change in Blood Glucose to Test Meal) | Week 16 (n=52, n=56, n=54, n=59) | 8.85 millimoles per liter (mmol/L)*minute | Standard Deviation 4.94 |
| Placebo | Meal Test Glucose Excursion (Change in Blood Glucose to Test Meal) | Baseline (n=63, n=62, n=66, n=63) | 10.76 millimoles per liter (mmol/L)*minute | Standard Deviation 4.37 |
| Placebo | Meal Test Glucose Excursion (Change in Blood Glucose to Test Meal) | Week 16 (n=52, n=56, n=54, n=59) | 10.94 millimoles per liter (mmol/L)*minute | Standard Deviation 4.79 |
p-value: <0.001ANCOVA
p-value: 0.047ANCOVA
p-value: 0.025ANCOVA
Secondary
Nausea and Dyspepsia Measured by Visual Analog Scale
Participants were asked to score nausea and dyspepsia (abdominal pain and bloating) on a scale of 0 (none) to 100 after the largest meal of the day.
Time frame: One week before and one week after each of the Baseline and Week 4 and Week 8 and Week 16 visits
Population: Participants who received at least one dose of LY2189265 or Placebo with evaluable nausea or dyspepsia (abdominal pain and bloating) data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1.0/2.0 Milligram (mg) LY2189265 | Nausea and Dyspepsia Measured by Visual Analog Scale | Bloating, Week before Week 16 (n=45, 49, 52, 54) | 12.57 units on a scale | Standard Deviation 18.93 |
| 1.0/2.0 Milligram (mg) LY2189265 | Nausea and Dyspepsia Measured by Visual Analog Scale | Nausea, Week before Week 16 (n=45, 49, 52, 54) | 9.68 units on a scale | Standard Deviation 17.79 |
| 1.0/2.0 Milligram (mg) LY2189265 | Nausea and Dyspepsia Measured by Visual Analog Scale | Nausea, Week before Week 8 (n=50, 51, 55, 58) | 10.90 units on a scale | Standard Deviation 20.26 |
| 1.0/2.0 Milligram (mg) LY2189265 | Nausea and Dyspepsia Measured by Visual Analog Scale | Ab pain, Week before Baseline (n=52, 57, 61, 57) | 5.66 units on a scale | Standard Deviation 11.37 |
| 1.0/2.0 Milligram (mg) LY2189265 | Nausea and Dyspepsia Measured by Visual Analog Scale | Nausea, Week after Week 8 (n=50, 54, 54, 55) | 8.58 units on a scale | Standard Deviation 12.88 |
| 1.0/2.0 Milligram (mg) LY2189265 | Nausea and Dyspepsia Measured by Visual Analog Scale | Bloating, Week after Week 8 (n=50, 54, 54, 55) | 13.30 units on a scale | Standard Deviation 18.66 |
| 1.0/2.0 Milligram (mg) LY2189265 | Nausea and Dyspepsia Measured by Visual Analog Scale | Ab pain, Week before Week 8 (n=50, 51, 55, 58) | 10.76 units on a scale | Standard Deviation 19.06 |
| 1.0/2.0 Milligram (mg) LY2189265 | Nausea and Dyspepsia Measured by Visual Analog Scale | Ab pain, Week after Week 8 (n=50, 54, 54, 55) | 7.97 units on a scale | Standard Deviation 14.72 |
| 1.0/2.0 Milligram (mg) LY2189265 | Nausea and Dyspepsia Measured by Visual Analog Scale | Bloating, Week before Week 8 (n=50, 51, 55, 58) | 17.65 units on a scale | Standard Deviation 26.41 |
| 1.0/2.0 Milligram (mg) LY2189265 | Nausea and Dyspepsia Measured by Visual Analog Scale | Ab pain, Week after Baseline (n=42, 46, 50, 50) | 5.82 units on a scale | Standard Deviation 9.41 |
| 1.0/2.0 Milligram (mg) LY2189265 | Nausea and Dyspepsia Measured by Visual Analog Scale | Nausea, Week before Baseline (n=52, 57, 61, 57) | 4.81 units on a scale | Standard Deviation 10.5 |
| 1.0/2.0 Milligram (mg) LY2189265 | Nausea and Dyspepsia Measured by Visual Analog Scale | Ab pain, Week after Week 16 (n=45, 48, 49, 53) | 7.56 units on a scale | Standard Deviation 14.28 |
| 1.0/2.0 Milligram (mg) LY2189265 | Nausea and Dyspepsia Measured by Visual Analog Scale | Bloating, Week before Baseline (n=52, 57, 61, 57) | 11.49 units on a scale | Standard Deviation 16.8 |
| 1.0/2.0 Milligram (mg) LY2189265 | Nausea and Dyspepsia Measured by Visual Analog Scale | Nausea, Week before Week 4 (n=42, 55, 52, 59) | 6.74 units on a scale | Standard Deviation 10.89 |
| 1.0/2.0 Milligram (mg) LY2189265 | Nausea and Dyspepsia Measured by Visual Analog Scale | Bloating, Week after Baseline (n=42, 46, 50, 50) | 8.95 units on a scale | Standard Deviation 12.9 |
| 1.0/2.0 Milligram (mg) LY2189265 | Nausea and Dyspepsia Measured by Visual Analog Scale | Nausea, Week after Week 4 (n=49, 58, 59, 54) | 18.13 units on a scale | Standard Deviation 24.52 |
| 1.0/2.0 Milligram (mg) LY2189265 | Nausea and Dyspepsia Measured by Visual Analog Scale | Ab pain, Week before Week 16 (n=45, 49, 52, 54) | 6.46 units on a scale | Standard Deviation 9.48 |
| 1.0/2.0 Milligram (mg) LY2189265 | Nausea and Dyspepsia Measured by Visual Analog Scale | Ab pain, Week before Week 4 (n=42, 55, 52, 59) | 6.28 units on a scale | Standard Deviation 9.53 |
| 1.0/2.0 Milligram (mg) LY2189265 | Nausea and Dyspepsia Measured by Visual Analog Scale | Nausea, Week after Baseline (n=42, 46, 50, 50) | 5.07 units on a scale | Standard Deviation 8.58 |
| 1.0/2.0 Milligram (mg) LY2189265 | Nausea and Dyspepsia Measured by Visual Analog Scale | Ab pain, Week after Week 4 (n=49, 58, 59, 54) | 12.47 units on a scale | Standard Deviation 20.44 |
| 1.0/2.0 Milligram (mg) LY2189265 | Nausea and Dyspepsia Measured by Visual Analog Scale | Nausea, Week after Week 16 (n=45, 48, 49, 53) | 11.09 units on a scale | Standard Deviation 17.62 |
| 1.0/2.0 Milligram (mg) LY2189265 | Nausea and Dyspepsia Measured by Visual Analog Scale | Bloating, Week before Week 4 (n=42, 55, 52, 59) | 13.56 units on a scale | Standard Deviation 19.51 |
| 1.0/2.0 Milligram (mg) LY2189265 | Nausea and Dyspepsia Measured by Visual Analog Scale | Bloating, Week after Week 16 (n=45, 48, 49, 53) | 14.06 units on a scale | Standard Deviation 20.46 |
| 1.0/2.0 Milligram (mg) LY2189265 | Nausea and Dyspepsia Measured by Visual Analog Scale | Bloating, Week after Week 4 (n=49, 58, 59, 54) | 19.90 units on a scale | Standard Deviation 25.61 |
| 1.0/1.0 Milligram (mg) LY2189265 | Nausea and Dyspepsia Measured by Visual Analog Scale | Nausea, Week before Baseline (n=52, 57, 61, 57) | 3.56 units on a scale | Standard Deviation 6.46 |
| 1.0/1.0 Milligram (mg) LY2189265 | Nausea and Dyspepsia Measured by Visual Analog Scale | Bloating, Week before Baseline (n=52, 57, 61, 57) | 8.11 units on a scale | Standard Deviation 18.04 |
| 1.0/1.0 Milligram (mg) LY2189265 | Nausea and Dyspepsia Measured by Visual Analog Scale | Nausea, Week after Week 16 (n=45, 48, 49, 53) | 5.73 units on a scale | Standard Deviation 10.8 |
| 1.0/1.0 Milligram (mg) LY2189265 | Nausea and Dyspepsia Measured by Visual Analog Scale | Nausea, Week before Week 8 (n=50, 51, 55, 58) | 5.45 units on a scale | Standard Deviation 10.63 |
| 1.0/1.0 Milligram (mg) LY2189265 | Nausea and Dyspepsia Measured by Visual Analog Scale | Nausea, Week before Week 4 (n=42, 55, 52, 59) | 6.88 units on a scale | Standard Deviation 11.47 |
| 1.0/1.0 Milligram (mg) LY2189265 | Nausea and Dyspepsia Measured by Visual Analog Scale | Bloating, Week after Week 8 (n=50, 54, 54, 55) | 11.18 units on a scale | Standard Deviation 19.56 |
| 1.0/1.0 Milligram (mg) LY2189265 | Nausea and Dyspepsia Measured by Visual Analog Scale | Bloating, Week before Week 4 (n=42, 55, 52, 59) | 12.00 units on a scale | Standard Deviation 19.17 |
| 1.0/1.0 Milligram (mg) LY2189265 | Nausea and Dyspepsia Measured by Visual Analog Scale | Nausea, Week after Week 8 (n=50, 54, 54, 55) | 5.57 units on a scale | Standard Deviation 11.5 |
| 1.0/1.0 Milligram (mg) LY2189265 | Nausea and Dyspepsia Measured by Visual Analog Scale | Ab pain, Week before Baseline (n=52, 57, 61, 57) | 3.55 units on a scale | Standard Deviation 9.14 |
| 1.0/1.0 Milligram (mg) LY2189265 | Nausea and Dyspepsia Measured by Visual Analog Scale | Ab pain, Week before Week 16 (n=45, 49, 52, 54) | 5.68 units on a scale | Standard Deviation 11.09 |
| 1.0/1.0 Milligram (mg) LY2189265 | Nausea and Dyspepsia Measured by Visual Analog Scale | Ab pain, Week after Week 4 (n=49, 58, 59, 54) | 9.31 units on a scale | Standard Deviation 15.77 |
| 1.0/1.0 Milligram (mg) LY2189265 | Nausea and Dyspepsia Measured by Visual Analog Scale | Ab pain, Week before Week 8 (n=50, 51, 55, 58) | 5.76 units on a scale | Standard Deviation 12.47 |
| 1.0/1.0 Milligram (mg) LY2189265 | Nausea and Dyspepsia Measured by Visual Analog Scale | Bloating, Week after Week 16 (n=45, 48, 49, 53) | 11.11 units on a scale | Standard Deviation 19.62 |
| 1.0/1.0 Milligram (mg) LY2189265 | Nausea and Dyspepsia Measured by Visual Analog Scale | Bloating, Week before Week 8 (n=50, 51, 55, 58) | 10.93 units on a scale | Standard Deviation 17.92 |
| 1.0/1.0 Milligram (mg) LY2189265 | Nausea and Dyspepsia Measured by Visual Analog Scale | Nausea, Week after Week 4 (n=49, 58, 59, 54) | 12.28 units on a scale | Standard Deviation 19.46 |
| 1.0/1.0 Milligram (mg) LY2189265 | Nausea and Dyspepsia Measured by Visual Analog Scale | Ab pain, Week after Week 8 (n=50, 54, 54, 55) | 6.87 units on a scale | Standard Deviation 14.56 |
| 1.0/1.0 Milligram (mg) LY2189265 | Nausea and Dyspepsia Measured by Visual Analog Scale | Ab pain, Week after Week 16 (n=45, 48, 49, 53) | 5.99 units on a scale | Standard Deviation 11.53 |
| 1.0/1.0 Milligram (mg) LY2189265 | Nausea and Dyspepsia Measured by Visual Analog Scale | Bloating, Week before Week 16 (n=45, 49, 52, 54) | 9.06 units on a scale | Standard Deviation 16.78 |
| 1.0/1.0 Milligram (mg) LY2189265 | Nausea and Dyspepsia Measured by Visual Analog Scale | Nausea, Week after Baseline (n=42, 46, 50, 50) | 3.85 units on a scale | Standard Deviation 6.46 |
| 1.0/1.0 Milligram (mg) LY2189265 | Nausea and Dyspepsia Measured by Visual Analog Scale | Ab pain, Week after Baseline (n=42, 46, 50, 50) | 4.89 units on a scale | Standard Deviation 13.35 |
| 1.0/1.0 Milligram (mg) LY2189265 | Nausea and Dyspepsia Measured by Visual Analog Scale | Bloating, Week after Week 4 (n=49, 58, 59, 54) | 13.40 units on a scale | Standard Deviation 21.15 |
| 1.0/1.0 Milligram (mg) LY2189265 | Nausea and Dyspepsia Measured by Visual Analog Scale | Ab pain, Week before Week 4 (n=42, 55, 52, 59) | 7.74 units on a scale | Standard Deviation 13.89 |
| 1.0/1.0 Milligram (mg) LY2189265 | Nausea and Dyspepsia Measured by Visual Analog Scale | Nausea, Week before Week 16 (n=45, 49, 52, 54) | 3.31 units on a scale | Standard Deviation 5.53 |
| 1.0/1.0 Milligram (mg) LY2189265 | Nausea and Dyspepsia Measured by Visual Analog Scale | Bloating, Week after Baseline (n=42, 46, 50, 50) | 10.10 units on a scale | Standard Deviation 16.64 |
| 0.5/1.0 Milligram (mg) LY2189265 | Nausea and Dyspepsia Measured by Visual Analog Scale | Ab pain, Week before Week 16 (n=45, 49, 52, 54) | 6.26 units on a scale | Standard Deviation 12.89 |
| 0.5/1.0 Milligram (mg) LY2189265 | Nausea and Dyspepsia Measured by Visual Analog Scale | Bloating, Week before Baseline (n=52, 57, 61, 57) | 10.21 units on a scale | Standard Deviation 15.32 |
| 0.5/1.0 Milligram (mg) LY2189265 | Nausea and Dyspepsia Measured by Visual Analog Scale | Nausea, Week after Week 16 (n=45, 48, 49, 53) | 7.77 units on a scale | Standard Deviation 12.25 |
| 0.5/1.0 Milligram (mg) LY2189265 | Nausea and Dyspepsia Measured by Visual Analog Scale | Nausea, Week before Baseline (n=52, 57, 61, 57) | 3.70 units on a scale | Standard Deviation 5.76 |
| 0.5/1.0 Milligram (mg) LY2189265 | Nausea and Dyspepsia Measured by Visual Analog Scale | Nausea, Week after Baseline (n=42, 46, 50, 50) | 3.86 units on a scale | Standard Deviation 5.96 |
| 0.5/1.0 Milligram (mg) LY2189265 | Nausea and Dyspepsia Measured by Visual Analog Scale | Ab pain, Week before Baseline (n=52, 57, 61, 57) | 4.04 units on a scale | Standard Deviation 7.15 |
| 0.5/1.0 Milligram (mg) LY2189265 | Nausea and Dyspepsia Measured by Visual Analog Scale | Ab pain, Week after Baseline (n=42, 46, 50, 50) | 4.51 units on a scale | Standard Deviation 8.6 |
| 0.5/1.0 Milligram (mg) LY2189265 | Nausea and Dyspepsia Measured by Visual Analog Scale | Bloating, Week after Baseline (n=42, 46, 50, 50) | 9.17 units on a scale | Standard Deviation 15.61 |
| 0.5/1.0 Milligram (mg) LY2189265 | Nausea and Dyspepsia Measured by Visual Analog Scale | Nausea, Week before Week 4 (n=42, 55, 52, 59) | 7.97 units on a scale | Standard Deviation 15.33 |
| 0.5/1.0 Milligram (mg) LY2189265 | Nausea and Dyspepsia Measured by Visual Analog Scale | Nausea, Week after Week 4 (n=49, 58, 59, 54) | 7.91 units on a scale | Standard Deviation 12.39 |
| 0.5/1.0 Milligram (mg) LY2189265 | Nausea and Dyspepsia Measured by Visual Analog Scale | Ab pain, Week before Week 4 (n=42, 55, 52, 59) | 6.38 units on a scale | Standard Deviation 11.13 |
| 0.5/1.0 Milligram (mg) LY2189265 | Nausea and Dyspepsia Measured by Visual Analog Scale | Ab pain, Week after Week 4 (n=49, 58, 59, 54) | 4.94 units on a scale | Standard Deviation 8.89 |
| 0.5/1.0 Milligram (mg) LY2189265 | Nausea and Dyspepsia Measured by Visual Analog Scale | Bloating, Week before Week 4 (n=42, 55, 52, 59) | 9.95 units on a scale | Standard Deviation 13.27 |
| 0.5/1.0 Milligram (mg) LY2189265 | Nausea and Dyspepsia Measured by Visual Analog Scale | Bloating, Week after Week 4 (n=49, 58, 59, 54) | 10.23 units on a scale | Standard Deviation 13.88 |
| 0.5/1.0 Milligram (mg) LY2189265 | Nausea and Dyspepsia Measured by Visual Analog Scale | Nausea, Week before Week 8 (n=50, 51, 55, 58) | 7.39 units on a scale | Standard Deviation 13.53 |
| 0.5/1.0 Milligram (mg) LY2189265 | Nausea and Dyspepsia Measured by Visual Analog Scale | Nausea, Week after Week 8 (n=50, 54, 54, 55) | 8.69 units on a scale | Standard Deviation 13.41 |
| 0.5/1.0 Milligram (mg) LY2189265 | Nausea and Dyspepsia Measured by Visual Analog Scale | Ab pain, Week before Week 8 (n=50, 51, 55, 58) | 5.12 units on a scale | Standard Deviation 9.01 |
| 0.5/1.0 Milligram (mg) LY2189265 | Nausea and Dyspepsia Measured by Visual Analog Scale | Ab pain, Week after Week 8 (n=50, 54, 54, 55) | 6.26 units on a scale | Standard Deviation 11.93 |
| 0.5/1.0 Milligram (mg) LY2189265 | Nausea and Dyspepsia Measured by Visual Analog Scale | Bloating, Week before Week 8 (n=50, 51, 55, 58) | 11.58 units on a scale | Standard Deviation 20.13 |
| 0.5/1.0 Milligram (mg) LY2189265 | Nausea and Dyspepsia Measured by Visual Analog Scale | Bloating, Week after Week 8 (n=50, 54, 54, 55) | 14.50 units on a scale | Standard Deviation 20.95 |
| 0.5/1.0 Milligram (mg) LY2189265 | Nausea and Dyspepsia Measured by Visual Analog Scale | Nausea, Week before Week 16 (n=45, 49, 52, 54) | 6.36 units on a scale | Standard Deviation 10.82 |
| 0.5/1.0 Milligram (mg) LY2189265 | Nausea and Dyspepsia Measured by Visual Analog Scale | Ab pain, Week after Week 16 (n=45, 48, 49, 53) | 6.44 units on a scale | Standard Deviation 12.58 |
| 0.5/1.0 Milligram (mg) LY2189265 | Nausea and Dyspepsia Measured by Visual Analog Scale | Bloating, Week before Week 16 (n=45, 49, 52, 54) | 12.26 units on a scale | Standard Deviation 20.06 |
| 0.5/1.0 Milligram (mg) LY2189265 | Nausea and Dyspepsia Measured by Visual Analog Scale | Bloating, Week after Week 16 (n=45, 48, 49, 53) | 14.04 units on a scale | Standard Deviation 22.26 |
| Placebo | Nausea and Dyspepsia Measured by Visual Analog Scale | Bloating, Week after Week 16 (n=45, 48, 49, 53) | 8.84 units on a scale | Standard Deviation 17.44 |
| Placebo | Nausea and Dyspepsia Measured by Visual Analog Scale | Bloating, Week after Week 8 (n=50, 54, 54, 55) | 10.34 units on a scale | Standard Deviation 17.17 |
| Placebo | Nausea and Dyspepsia Measured by Visual Analog Scale | Bloating, Week after Week 4 (n=49, 58, 59, 54) | 8.40 units on a scale | Standard Deviation 14.96 |
| Placebo | Nausea and Dyspepsia Measured by Visual Analog Scale | Bloating, Week before Week 4 (n=42, 55, 52, 59) | 7.96 units on a scale | Standard Deviation 15.77 |
| Placebo | Nausea and Dyspepsia Measured by Visual Analog Scale | Bloating, Week before Week 16 (n=45, 49, 52, 54) | 9.30 units on a scale | Standard Deviation 18.6 |
| Placebo | Nausea and Dyspepsia Measured by Visual Analog Scale | Nausea, Week before Week 16 (n=45, 49, 52, 54) | 5.88 units on a scale | Standard Deviation 14.41 |
| Placebo | Nausea and Dyspepsia Measured by Visual Analog Scale | Ab pain, Week after Week 4 (n=49, 58, 59, 54) | 4.59 units on a scale | Standard Deviation 7.88 |
| Placebo | Nausea and Dyspepsia Measured by Visual Analog Scale | Ab pain, Week before Week 4 (n=42, 55, 52, 59) | 4.45 units on a scale | Standard Deviation 9.19 |
| Placebo | Nausea and Dyspepsia Measured by Visual Analog Scale | Nausea, Week after Week 16 (n=45, 48, 49, 53) | 3.40 units on a scale | Standard Deviation 6.4 |
| Placebo | Nausea and Dyspepsia Measured by Visual Analog Scale | Nausea, Week after Week 4 (n=49, 58, 59, 54) | 4.10 units on a scale | Standard Deviation 7.57 |
| Placebo | Nausea and Dyspepsia Measured by Visual Analog Scale | Nausea, Week before Week 4 (n=42, 55, 52, 59) | 4.10 units on a scale | Standard Deviation 7.32 |
| Placebo | Nausea and Dyspepsia Measured by Visual Analog Scale | Bloating, Week after Baseline (n=42, 46, 50, 50) | 8.42 units on a scale | Standard Deviation 20.05 |
| Placebo | Nausea and Dyspepsia Measured by Visual Analog Scale | Ab pain, Week before Week 16 (n=45, 49, 52, 54) | 6.17 units on a scale | Standard Deviation 14.24 |
| Placebo | Nausea and Dyspepsia Measured by Visual Analog Scale | Ab pain, Week after Baseline (n=42, 46, 50, 50) | 2.86 units on a scale | Standard Deviation 7.27 |
| Placebo | Nausea and Dyspepsia Measured by Visual Analog Scale | Ab pain, Week before Baseline (n=52, 57, 61, 57) | 3.63 units on a scale | Standard Deviation 6.58 |
| Placebo | Nausea and Dyspepsia Measured by Visual Analog Scale | Bloating, Week before Baseline (n=52, 57, 61, 57) | 9.30 units on a scale | Standard Deviation 18.65 |
| Placebo | Nausea and Dyspepsia Measured by Visual Analog Scale | Ab pain, Week after Week 16 (n=45, 48, 49, 53) | 5.19 units on a scale | Standard Deviation 11.72 |
| Placebo | Nausea and Dyspepsia Measured by Visual Analog Scale | Nausea, Week after Baseline (n=42, 46, 50, 50) | 2.25 units on a scale | Standard Deviation 4.82 |
| Placebo | Nausea and Dyspepsia Measured by Visual Analog Scale | Ab pain, Week after Week 8 (n=50, 54, 54, 55) | 6.38 units on a scale | Standard Deviation 12.74 |
| Placebo | Nausea and Dyspepsia Measured by Visual Analog Scale | Ab pain, Week before Week 8 (n=50, 51, 55, 58) | 6.65 units on a scale | Standard Deviation 13.15 |
| Placebo | Nausea and Dyspepsia Measured by Visual Analog Scale | Nausea, Week before Baseline (n=52, 57, 61, 57) | 3.35 units on a scale | Standard Deviation 5.83 |
| Placebo | Nausea and Dyspepsia Measured by Visual Analog Scale | Bloating, Week before Week 8 (n=50, 51, 55, 58) | 10.12 units on a scale | Standard Deviation 19.2 |
| Placebo | Nausea and Dyspepsia Measured by Visual Analog Scale | Nausea, Week after Week 8 (n=50, 54, 54, 55) | 5.30 units on a scale | Standard Deviation 11.52 |
| Placebo | Nausea and Dyspepsia Measured by Visual Analog Scale | Nausea, Week before Week 8 (n=50, 51, 55, 58) | 6.11 units on a scale | Standard Deviation 12.59 |
Secondary
Number of Participants With a Hypoglycemic Event
A documented hypoglycemic episode is defined as an event which is associated with a measured blood glucose of ≤70 milligrams per deciliter (mg/dL) (3.9 millimoles per liter \[mmol/L\]), even if it was not associated with symptoms, signs, or treatment. A severe hypoglycemic episode is defined as an event with a measured blood glucose of \<50mg/dL. Participant reports of hypoglycemic events were collected at the beginning of each visit starting at Baseline. 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 4, 8, and 16 weeks
Population: Participants who received at least one dose of LY2189265 or Placebo.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 1.0/2.0 Milligram (mg) LY2189265 | Number of Participants With a Hypoglycemic Event | Severe Hypoglycemic Event, Week 8 | 0 participants |
| 1.0/2.0 Milligram (mg) LY2189265 | Number of Participants With a Hypoglycemic Event | Documented Hypoglycemic Event, Week 8 | 11 participants |
| 1.0/2.0 Milligram (mg) LY2189265 | Number of Participants With a Hypoglycemic Event | Severe Hypoglycemic Event, Week 16 | 0 participants |
| 1.0/2.0 Milligram (mg) LY2189265 | Number of Participants With a Hypoglycemic Event | Documented Hypoglycemic Event, Week 16 | 6 participants |
| 1.0/2.0 Milligram (mg) LY2189265 | Number of Participants With a Hypoglycemic Event | Severe Hypoglycemic Event, Week 4 | 0 participants |
| 1.0/2.0 Milligram (mg) LY2189265 | Number of Participants With a Hypoglycemic Event | Documented Hypoglycemic Event, Week 4 | 17 participants |
| 1.0/1.0 Milligram (mg) LY2189265 | Number of Participants With a Hypoglycemic Event | Documented Hypoglycemic Event, Week 8 | 13 participants |
| 1.0/1.0 Milligram (mg) LY2189265 | Number of Participants With a Hypoglycemic Event | Documented Hypoglycemic Event, Week 4 | 17 participants |
| 1.0/1.0 Milligram (mg) LY2189265 | Number of Participants With a Hypoglycemic Event | Documented Hypoglycemic Event, Week 16 | 10 participants |
| 1.0/1.0 Milligram (mg) LY2189265 | Number of Participants With a Hypoglycemic Event | Severe Hypoglycemic Event, Week 8 | 0 participants |
| 1.0/1.0 Milligram (mg) LY2189265 | Number of Participants With a Hypoglycemic Event | Severe Hypoglycemic Event, Week 16 | 0 participants |
| 1.0/1.0 Milligram (mg) LY2189265 | Number of Participants With a Hypoglycemic Event | Severe Hypoglycemic Event, Week 4 | 0 participants |
| 0.5/1.0 Milligram (mg) LY2189265 | Number of Participants With a Hypoglycemic Event | Documented Hypoglycemic Event, Week 4 | 17 participants |
| 0.5/1.0 Milligram (mg) LY2189265 | Number of Participants With a Hypoglycemic Event | Documented Hypoglycemic Event, Week 8 | 15 participants |
| 0.5/1.0 Milligram (mg) LY2189265 | Number of Participants With a Hypoglycemic Event | Severe Hypoglycemic Event, Week 8 | 0 participants |
| 0.5/1.0 Milligram (mg) LY2189265 | Number of Participants With a Hypoglycemic Event | Severe Hypoglycemic Event, Week 4 | 0 participants |
| 0.5/1.0 Milligram (mg) LY2189265 | Number of Participants With a Hypoglycemic Event | Severe Hypoglycemic Event, Week 16 | 0 participants |
| 0.5/1.0 Milligram (mg) LY2189265 | Number of Participants With a Hypoglycemic Event | Documented Hypoglycemic Event, Week 16 | 7 participants |
| Placebo | Number of Participants With a Hypoglycemic Event | Severe Hypoglycemic Event, Week 16 | 0 participants |
| Placebo | Number of Participants With a Hypoglycemic Event | Documented Hypoglycemic Event, Week 4 | 9 participants |
| Placebo | Number of Participants With a Hypoglycemic Event | Documented Hypoglycemic Event, Week 8 | 10 participants |
| Placebo | Number of Participants With a Hypoglycemic Event | Documented Hypoglycemic Event, Week 16 | 8 participants |
| Placebo | Number of Participants With a Hypoglycemic Event | Severe Hypoglycemic Event, Week 4 | 0 participants |
| Placebo | Number of Participants With a Hypoglycemic Event | Severe Hypoglycemic Event, Week 8 | 0 participants |
Secondary
Participants Perception of Medication Effectiveness Using the Perceptions About Medications - Diabetes, Short Version (PAM-D-S) Questionnaire
The Perceptions about Medications - Diabetes, Short Version (PAM-D-S) questionnaire consisted of: 2 items in which respondents were asked about their satisfaction with their diabetes medication over the past week using a 6-point scale ranging from 1 completely dissatisfied to 6 completely satisfied; 10 items in which respondents were asked about the effectiveness of their diabetes medications in the past week using a 4-point scale ranging from 1 all of the time to 4 none of the time; and 15 items asking respondents to indicate the frequency of physical side effects in the past week using a 4-point scale ranging from 1 all of the time to 4 none of the time. These items were exploratory items taken from a Diabetes Medicines Survey and had not been validated as a scale. The percentage of participants that rated their general health as good or better are summarized.
Time frame: Baseline and 4 and 8 and 16 weeks
Population: Participants in the per-protocol population with evaluable PAM-D-S questionnaire data. The per-protocol population consisted of participants who received at least one dose of study medication, had no significant protocol violations, completed the double-blind treatment phase, and were compliant with the study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 1.0/2.0 Milligram (mg) LY2189265 | Participants Perception of Medication Effectiveness Using the Perceptions About Medications - Diabetes, Short Version (PAM-D-S) Questionnaire | Baseline | 72.7 percentage of participants |
| 1.0/2.0 Milligram (mg) LY2189265 | Participants Perception of Medication Effectiveness Using the Perceptions About Medications - Diabetes, Short Version (PAM-D-S) Questionnaire | Week 4 | 83.3 percentage of participants |
| 1.0/2.0 Milligram (mg) LY2189265 | Participants Perception of Medication Effectiveness Using the Perceptions About Medications - Diabetes, Short Version (PAM-D-S) Questionnaire | Week 8 | 82.9 percentage of participants |
| 1.0/2.0 Milligram (mg) LY2189265 | Participants Perception of Medication Effectiveness Using the Perceptions About Medications - Diabetes, Short Version (PAM-D-S) Questionnaire | Week 16 | 92.1 percentage of participants |
| 1.0/1.0 Milligram (mg) LY2189265 | Participants Perception of Medication Effectiveness Using the Perceptions About Medications - Diabetes, Short Version (PAM-D-S) Questionnaire | Week 4 | 90.2 percentage of participants |
| 1.0/1.0 Milligram (mg) LY2189265 | Participants Perception of Medication Effectiveness Using the Perceptions About Medications - Diabetes, Short Version (PAM-D-S) Questionnaire | Week 8 | 90.5 percentage of participants |
| 1.0/1.0 Milligram (mg) LY2189265 | Participants Perception of Medication Effectiveness Using the Perceptions About Medications - Diabetes, Short Version (PAM-D-S) Questionnaire | Week 16 | 90.2 percentage of participants |
| 1.0/1.0 Milligram (mg) LY2189265 | Participants Perception of Medication Effectiveness Using the Perceptions About Medications - Diabetes, Short Version (PAM-D-S) Questionnaire | Baseline | 87.0 percentage of participants |
| 0.5/1.0 Milligram (mg) LY2189265 | Participants Perception of Medication Effectiveness Using the Perceptions About Medications - Diabetes, Short Version (PAM-D-S) Questionnaire | Week 8 | 90.9 percentage of participants |
| 0.5/1.0 Milligram (mg) LY2189265 | Participants Perception of Medication Effectiveness Using the Perceptions About Medications - Diabetes, Short Version (PAM-D-S) Questionnaire | Week 4 | 87.5 percentage of participants |
| 0.5/1.0 Milligram (mg) LY2189265 | Participants Perception of Medication Effectiveness Using the Perceptions About Medications - Diabetes, Short Version (PAM-D-S) Questionnaire | Week 16 | 86.0 percentage of participants |
| 0.5/1.0 Milligram (mg) LY2189265 | Participants Perception of Medication Effectiveness Using the Perceptions About Medications - Diabetes, Short Version (PAM-D-S) Questionnaire | Baseline | 87.5 percentage of participants |
| Placebo | Participants Perception of Medication Effectiveness Using the Perceptions About Medications - Diabetes, Short Version (PAM-D-S) Questionnaire | Week 16 | 93.0 percentage of participants |
| Placebo | Participants Perception of Medication Effectiveness Using the Perceptions About Medications - Diabetes, Short Version (PAM-D-S) Questionnaire | Week 4 | 87.0 percentage of participants |
| Placebo | Participants Perception of Medication Effectiveness Using the Perceptions About Medications - Diabetes, Short Version (PAM-D-S) Questionnaire | Baseline | 89.1 percentage of participants |
| Placebo | Participants Perception of Medication Effectiveness Using the Perceptions About Medications - Diabetes, Short Version (PAM-D-S) Questionnaire | Week 8 | 88.6 percentage of participants |
Secondary
Percentage of Participants Achieving a Glycosylated Hemoglobin (HbA1c) of <7% or ≤6.5%
Percentages of participants who achieved glycosylated hemoglobin (HbA1c) levels of \<7% or ≤6.5% were analyzed with a logistic regression model with baseline, combination of oral medications, and treatment as factors included in the model.
Time frame: Baseline and 4 and 8 and 16 weeks
Population: Participants who received at least one dose of LY2189265 or Placebo with evaluable glycosylated hemoglobin (HbA1c) data. For Week 16 data, last observation carried forward (LOCF) was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 1.0/2.0 Milligram (mg) LY2189265 | Percentage of Participants Achieving a Glycosylated Hemoglobin (HbA1c) of <7% or ≤6.5% | HbA1c levels ≤6.5%, Week 8 | 20.0 percentage of participants |
| 1.0/2.0 Milligram (mg) LY2189265 | Percentage of Participants Achieving a Glycosylated Hemoglobin (HbA1c) of <7% or ≤6.5% | HbA1c levels ≤6.5%, Week 16 | 32.3 percentage of participants |
| 1.0/2.0 Milligram (mg) LY2189265 | Percentage of Participants Achieving a Glycosylated Hemoglobin (HbA1c) of <7% or ≤6.5% | HbA1c levels <7.0%, Week 4 | 15.4 percentage of participants |
| 1.0/2.0 Milligram (mg) LY2189265 | Percentage of Participants Achieving a Glycosylated Hemoglobin (HbA1c) of <7% or ≤6.5% | HbA1c levels <7%, Week 8 | 41.5 percentage of participants |
| 1.0/2.0 Milligram (mg) LY2189265 | Percentage of Participants Achieving a Glycosylated Hemoglobin (HbA1c) of <7% or ≤6.5% | HbA1c levels <7.0%, Baseline | 3.1 percentage of participants |
| 1.0/2.0 Milligram (mg) LY2189265 | Percentage of Participants Achieving a Glycosylated Hemoglobin (HbA1c) of <7% or ≤6.5% | HbA1c levels ≤6.5%, Baseline | 0.0 percentage of participants |
| 1.0/2.0 Milligram (mg) LY2189265 | Percentage of Participants Achieving a Glycosylated Hemoglobin (HbA1c) of <7% or ≤6.5% | HbA1c levels ≤6.5%, Week 4 | 4.6 percentage of participants |
| 1.0/2.0 Milligram (mg) LY2189265 | Percentage of Participants Achieving a Glycosylated Hemoglobin (HbA1c) of <7% or ≤6.5% | HbA1c levels <7%, Week 16 | 53.8 percentage of participants |
| 1.0/1.0 Milligram (mg) LY2189265 | Percentage of Participants Achieving a Glycosylated Hemoglobin (HbA1c) of <7% or ≤6.5% | HbA1c levels ≤6.5%, Week 4 | 7.7 percentage of participants |
| 1.0/1.0 Milligram (mg) LY2189265 | Percentage of Participants Achieving a Glycosylated Hemoglobin (HbA1c) of <7% or ≤6.5% | HbA1c levels ≤6.5%, Week 8 | 26.2 percentage of participants |
| 1.0/1.0 Milligram (mg) LY2189265 | Percentage of Participants Achieving a Glycosylated Hemoglobin (HbA1c) of <7% or ≤6.5% | HbA1c levels ≤6.5%, Week 16 | 32.3 percentage of participants |
| 1.0/1.0 Milligram (mg) LY2189265 | Percentage of Participants Achieving a Glycosylated Hemoglobin (HbA1c) of <7% or ≤6.5% | HbA1c levels ≤6.5%, Baseline | 1.5 percentage of participants |
| 1.0/1.0 Milligram (mg) LY2189265 | Percentage of Participants Achieving a Glycosylated Hemoglobin (HbA1c) of <7% or ≤6.5% | HbA1c levels <7.0%, Baseline | 4.6 percentage of participants |
| 1.0/1.0 Milligram (mg) LY2189265 | Percentage of Participants Achieving a Glycosylated Hemoglobin (HbA1c) of <7% or ≤6.5% | HbA1c levels <7.0%, Week 4 | 30.8 percentage of participants |
| 1.0/1.0 Milligram (mg) LY2189265 | Percentage of Participants Achieving a Glycosylated Hemoglobin (HbA1c) of <7% or ≤6.5% | HbA1c levels <7%, Week 16 | 50.8 percentage of participants |
| 1.0/1.0 Milligram (mg) LY2189265 | Percentage of Participants Achieving a Glycosylated Hemoglobin (HbA1c) of <7% or ≤6.5% | HbA1c levels <7%, Week 8 | 47.7 percentage of participants |
| 0.5/1.0 Milligram (mg) LY2189265 | Percentage of Participants Achieving a Glycosylated Hemoglobin (HbA1c) of <7% or ≤6.5% | HbA1c levels ≤6.5%, Week 4 | 3.0 percentage of participants |
| 0.5/1.0 Milligram (mg) LY2189265 | Percentage of Participants Achieving a Glycosylated Hemoglobin (HbA1c) of <7% or ≤6.5% | HbA1c levels <7%, Week 8 | 47.0 percentage of participants |
| 0.5/1.0 Milligram (mg) LY2189265 | Percentage of Participants Achieving a Glycosylated Hemoglobin (HbA1c) of <7% or ≤6.5% | HbA1c levels <7.0%, Baseline | 1.5 percentage of participants |
| 0.5/1.0 Milligram (mg) LY2189265 | Percentage of Participants Achieving a Glycosylated Hemoglobin (HbA1c) of <7% or ≤6.5% | HbA1c levels ≤6.5%, Baseline | 0.0 percentage of participants |
| 0.5/1.0 Milligram (mg) LY2189265 | Percentage of Participants Achieving a Glycosylated Hemoglobin (HbA1c) of <7% or ≤6.5% | HbA1c levels <7.0%, Week 4 | 22.7 percentage of participants |
| 0.5/1.0 Milligram (mg) LY2189265 | Percentage of Participants Achieving a Glycosylated Hemoglobin (HbA1c) of <7% or ≤6.5% | HbA1c levels ≤6.5%, Week 8 | 18.2 percentage of participants |
| 0.5/1.0 Milligram (mg) LY2189265 | Percentage of Participants Achieving a Glycosylated Hemoglobin (HbA1c) of <7% or ≤6.5% | HbA1c levels <7%, Week 16 | 56.1 percentage of participants |
| 0.5/1.0 Milligram (mg) LY2189265 | Percentage of Participants Achieving a Glycosylated Hemoglobin (HbA1c) of <7% or ≤6.5% | HbA1c levels ≤6.5%, Week 16 | 33.3 percentage of participants |
| Placebo | Percentage of Participants Achieving a Glycosylated Hemoglobin (HbA1c) of <7% or ≤6.5% | HbA1c levels ≤6.5%, Week 4 | 1.5 percentage of participants |
| Placebo | Percentage of Participants Achieving a Glycosylated Hemoglobin (HbA1c) of <7% or ≤6.5% | HbA1c levels <7.0%, Week 4 | 7.6 percentage of participants |
| Placebo | Percentage of Participants Achieving a Glycosylated Hemoglobin (HbA1c) of <7% or ≤6.5% | HbA1c levels ≤6.5%, Week 16 | 4.5 percentage of participants |
| Placebo | Percentage of Participants Achieving a Glycosylated Hemoglobin (HbA1c) of <7% or ≤6.5% | HbA1c levels <7%, Week 16 | 15.2 percentage of participants |
| Placebo | Percentage of Participants Achieving a Glycosylated Hemoglobin (HbA1c) of <7% or ≤6.5% | HbA1c levels ≤6.5%, Baseline | 0.0 percentage of participants |
| Placebo | Percentage of Participants Achieving a Glycosylated Hemoglobin (HbA1c) of <7% or ≤6.5% | HbA1c levels <7%, Week 8 | 15.2 percentage of participants |
| Placebo | Percentage of Participants Achieving a Glycosylated Hemoglobin (HbA1c) of <7% or ≤6.5% | HbA1c levels <7.0%, Baseline | 4.5 percentage of participants |
| Placebo | Percentage of Participants Achieving a Glycosylated Hemoglobin (HbA1c) of <7% or ≤6.5% | HbA1c levels ≤6.5%, Week 8 | 1.5 percentage of participants |
Secondary
Pharmacokinetics (PK) of LY2189265 - Area Under the Concentration Time Curve (AUC)
The population mean estimates and standard deviations were calculated for pharmacokinetic parameters (area under the concentration time curve \[AUC\] at steady state from time zero to 168 hours after study drug administration).
Time frame: Time zero to 168 hours after study drug administration at 4, 8, and 16 weeks
Population: Participants who received at least one dose of LY2189265 with evaluable LY2189265 concentration data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 1.0/2.0 Milligram (mg) LY2189265 | Pharmacokinetics (PK) of LY2189265 - Area Under the Concentration Time Curve (AUC) | 14587 nanograms*hour/milliliter (ng*h/mL) | Standard Deviation 5674 |
| 1.0/1.0 Milligram (mg) LY2189265 | Pharmacokinetics (PK) of LY2189265 - Area Under the Concentration Time Curve (AUC) | 7876 nanograms*hour/milliliter (ng*h/mL) | Standard Deviation 3064 |
| 0.5/1.0 Milligram (mg) LY2189265 | Pharmacokinetics (PK) of LY2189265 - Area Under the Concentration Time Curve (AUC) | 4488 nanograms*hour/milliliter (ng*h/mL) | Standard Deviation 1746 |
Secondary
Rate of Hypoglycemia Per 30 Days
Hypoglycemic episodes are defined as an event which is associated with reported signs and/or symptoms of hypoglycemia (for example, sweating, shakiness, tachycardia, etc.) or a documented blood glucose (BG) concentration of ≤70 milligrams per deciliter (mg/dL) (3.9 millimoles per liter \[mmol/L\]), even if it was not associated with symptoms, signs, or treatment. The rate is the average number of days out of 30 that a participant reported hypoglycemia. 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 16 weeks
Population: Participants who received at least one dose of LY2189265 or Placebo.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 1.0/2.0 Milligram (mg) LY2189265 | Rate of Hypoglycemia Per 30 Days | 0.69 events per participant per 30 days | Standard Deviation 1.29 |
| 1.0/1.0 Milligram (mg) LY2189265 | Rate of Hypoglycemia Per 30 Days | 0.80 events per participant per 30 days | Standard Deviation 1.6 |
| 0.5/1.0 Milligram (mg) LY2189265 | Rate of Hypoglycemia Per 30 Days | 0.70 events per participant per 30 days | Standard Deviation 1.18 |
| Placebo | Rate of Hypoglycemia Per 30 Days | 0.24 events per participant per 30 days | Standard Deviation 0.54 |
Secondary
Validation of the Psychometric Properties of the Perceptions About Medications - Diabetes, Short Version (PAM-D-S) Questionnaire
This purpose of this outcome measure was to validate the PAM-D-S questionnaire for future use. Please refer to Outcome Measure #14 for a description of the PAM-D-S questionnaire and results collected. A preliminary analysis indicated modifications to the questionnaire were required and further study is necessary to complete the validation. Therefore, the PAM-D-S questionnaire was not validated as a part of Study H9X-MC-GBCJ.
Time frame: Baseline and 4 and 8 and 16 weeks
Population: The items in the Perceptions about Medications - Diabetes, Short Version (PAM-D-S) questionnaire were exploratory items taken from a Diabetes Medicines Survey and had not been validated as a scale. Therefore, no participants were analyzed for validation purposes.