Type 2 Diabetes Mellitus
Conditions
Brief summary
The reason for this study is to see if insulin glargine is safe in participants with type 2 diabetes mellitus (T2DM) in India.
Interventions
DRUGInsulin Glargine
Administered SC
Sponsors
Eli Lilly and Company
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Have T2DM based on the disease diagnostic criteria from the World Health Organization (WHO) classification for at least 6 months before screening. * Have been receiving glucagon-like peptide-1 receptor agonist (GLP-1 RA) or ≥2 oral antihyperglycemic medication (OAMs) at stable doses for 90 days prior to screening. * Have an HbA1c level ≥7.0% and \<11.0%. * Have never been treated with insulins except for short term treatment of acute conditions up to a maximum of 14 days.
Exclusion criteria
* Have any form of diabetes other than T2DM. * Have hypersensitivity to the active substance of LY2963016 or to any of the excipients. * Have any clinically significant disorder, other than T2DM, that in the investigator's opinion, would preclude participation in the trial. * Are receiving systemic glucocorticosteroids therapy or have excessive insulin resistance (total insulin dose \>2 units per kilogram). * Have a history or diagnosis of human immunodeficiency virus infection, hepatitis B and C. * Have comorbidities of unstable angina, cardiac failure (Stage III or IV as per New York Heart Association guidelines) or renal failure (estimated glomerular filtration rate \<30 milliliters/minute/meter squared). * Are pregnant or intend to become pregnant during the course of the study; or are sexually active women of child-bearing potential not actively practicing birth control by a medically acceptable method as determined by the investigator. * Is a woman who is breastfeeding. * Have participated within the last 30 days in a clinical trial involving an investigational product other than the LY2963016. If the previous investigational product has a long half-life, 3 months or 5 half-lives (whichever is longer) should have passed. * Have previously completed or withdrawn from this study or any other study investigating LY2963016. This exclusion criterion does not apply to participants who are rescreened prior to baseline visit. * Are currently enrolled in any other clinical study involving an investigational product or any other type of medical research judged not to be scientifically or medically compatible with this study. * Are unwilling or unable to comply with the use of a glucometer.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number or Participants With Hypoglycemic Events | Baseline to Week 24 | Hypoglycemic event is when the fasting blood glucose (FBG) level is ≤ 54 milligrams per deciliter (mg/dL) \[≤ 3.0 millimoles per liter (mmol/L)\]. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Basal Insulin Dose | Week 24 | Basal Insulin Dose at Week 24. |
| Change From Baseline in Body Weight | Baseline, Week 24 | Change from baseline in body weight was evaluated. Least Square (LS) mean was calculated using generalized linear model with the analysis variable as outcome, and the baseline of the analysis variable as covariate. |
| Change From Baseline in Hemoglobin A1c (HbA1c) | Baseline, Week 12 and Week 24 | HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time. LS mean was calculated using generalized linear model with the analysis variable as outcome, and the baseline of analysis variable as covariate. |
| Change From Baseline in 7-Point Self-Monitoring Blood Glucose (SMBG) Values | Baseline, Week 24 | Seven-point SMBG was completed at the following timepoints: Before Breakfast, 2 Hours After Morning Meal, Before Mid-Day Meal, 2 Hours After Mid-Day Meal, Before Evening Meal, 2 Hours After Evening Meal and at 3 AM (± 1 hour). LS mean was calculated using generalized linear model with the analysis variable as outcome, and the baseline of analysis variable as covariate. |
| Change From Week 4 in Insulin Treatment Satisfaction Questionnaire (ITSQ) | Baseline (Week 4), Week 24 | The ITSQ is a 22-item questionnaire that assesses treatment satisfaction for participants taking insulin, under 5 domains: Inconvenience of Regimen \[(IR) - 5 items\], Lifestyle Flexibility \[(LF) - 3 items\], Glycemic Control \[(GC) - 3 items\], Hypoglycemic Control \[(HC) - 5 items\], Insulin Delivery Device \[(IDD) - 6 items\]. Each Item is measured on a 7-point scale, with scores ranging for IR from 5 to 35, LF from 3 to 21, GC from 3 to 21, HC from 5 to 35, IDD from 6 to 42. Lower scores reflect better outcomes. LS mean was calculated using generalized linear model with the analysis variable as outcome, and the baseline of analysis variable as covariate. ITSQ was not evaluated at Week 0. For this outcome, Week 4 was considered as baseline. |
Countries
India
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Insulin Glargine Participants received insulin glargine QD SC with a starting dose of 10 units. Participants self-titrated once or twice weekly until fasting blood glucose level was lowered to \<100 mg/dL. Dose was reduced by 4 units in case of hypoglycemia. | 259 |
| Total | 259 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Covid 19 | 52 |
| Overall Study | Death | 1 |
| Overall Study | Due to Low Fasting Blood Sugar Levels | 1 |
| Overall Study | Due to Unavailable Glucometer | 1 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Participant Dropped Out as Required Laboratory Test was Not Performed | 5 |
| Overall Study | Physician Decision | 1 |
| Overall Study | Withdrawal by Subject | 24 |
Baseline characteristics
| Characteristic | Insulin Glargine |
|---|---|
| Age, Continuous | 52.1 years STANDARD_DEVIATION 11.38 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 259 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Region of Enrollment India | 259 Participants |
| Sex: Female, Male Female | 93 Participants |
| Sex: Female, Male Male | 166 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 259 |
| other Total, other adverse events | 8 / 259 |
| serious Total, serious adverse events | 1 / 259 |
Outcome results
Primary
Number or Participants With Hypoglycemic Events
Hypoglycemic event is when the fasting blood glucose (FBG) level is ≤ 54 milligrams per deciliter (mg/dL) \[≤ 3.0 millimoles per liter (mmol/L)\].
Time frame: Baseline to Week 24
Population: All participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Insulin Glargine | Number or Participants With Hypoglycemic Events | 10 participants |
Secondary
Basal Insulin Dose
Basal Insulin Dose at Week 24.
Time frame: Week 24
Population: All participants who received at least one dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin Glargine | Basal Insulin Dose | 0.30 Units per kilograms per day (U/kg/day) | Standard Deviation 0.116 |
Secondary
Change From Baseline in 7-Point Self-Monitoring Blood Glucose (SMBG) Values
Seven-point SMBG was completed at the following timepoints: Before Breakfast, 2 Hours After Morning Meal, Before Mid-Day Meal, 2 Hours After Mid-Day Meal, Before Evening Meal, 2 Hours After Evening Meal and at 3 AM (± 1 hour). LS mean was calculated using generalized linear model with the analysis variable as outcome, and the baseline of analysis variable as covariate.
Time frame: Baseline, Week 24
Population: All participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Glargine | Change From Baseline in 7-Point Self-Monitoring Blood Glucose (SMBG) Values | Blood glucose concentration 2 hours after morning meal | -54.3 milligrams per deciliter (mg/dL) | Standard Error 2.87 |
| Insulin Glargine | Change From Baseline in 7-Point Self-Monitoring Blood Glucose (SMBG) Values | Blood glucose concentration before midday meal | -32.9 milligrams per deciliter (mg/dL) | Standard Error 2.52 |
| Insulin Glargine | Change From Baseline in 7-Point Self-Monitoring Blood Glucose (SMBG) Values | Blood glucose concentration before breakfast | -38.7 milligrams per deciliter (mg/dL) | Standard Error 2.12 |
| Insulin Glargine | Change From Baseline in 7-Point Self-Monitoring Blood Glucose (SMBG) Values | Blood glucose concentration 2 hours after midday meal | -43.6 milligrams per deciliter (mg/dL) | Standard Error 2.98 |
| Insulin Glargine | Change From Baseline in 7-Point Self-Monitoring Blood Glucose (SMBG) Values | Blood glucose concentration before evening meal | -29.4 milligrams per deciliter (mg/dL) | Standard Error 2.41 |
| Insulin Glargine | Change From Baseline in 7-Point Self-Monitoring Blood Glucose (SMBG) Values | Blood glucose concentration 2 hours after evening meal | -45.7 milligrams per deciliter (mg/dL) | Standard Error 2.97 |
| Insulin Glargine | Change From Baseline in 7-Point Self-Monitoring Blood Glucose (SMBG) Values | Blood glucose concentration at 3AM (± 1 hour) | -32.9 milligrams per deciliter (mg/dL) | Standard Error 2.2 |
Secondary
Change From Baseline in Body Weight
Change from baseline in body weight was evaluated. Least Square (LS) mean was calculated using generalized linear model with the analysis variable as outcome, and the baseline of the analysis variable as covariate.
Time frame: Baseline, Week 24
Population: All participants who received at least one dose of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Insulin Glargine | Change From Baseline in Body Weight | -0.5 kilogram (kg) | Standard Error 0.15 |
Secondary
Change From Baseline in Hemoglobin A1c (HbA1c)
HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time. LS mean was calculated using generalized linear model with the analysis variable as outcome, and the baseline of analysis variable as covariate.
Time frame: Baseline, Week 12 and Week 24
Population: All participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Glargine | Change From Baseline in Hemoglobin A1c (HbA1c) | At Week 12 | -0.641 Percentage of HbA1c | Standard Error 0.0719 |
| Insulin Glargine | Change From Baseline in Hemoglobin A1c (HbA1c) | At Week 24 | -0.860 Percentage of HbA1c | Standard Error 0.0847 |
Secondary
Change From Week 4 in Insulin Treatment Satisfaction Questionnaire (ITSQ)
The ITSQ is a 22-item questionnaire that assesses treatment satisfaction for participants taking insulin, under 5 domains: Inconvenience of Regimen \[(IR) - 5 items\], Lifestyle Flexibility \[(LF) - 3 items\], Glycemic Control \[(GC) - 3 items\], Hypoglycemic Control \[(HC) - 5 items\], Insulin Delivery Device \[(IDD) - 6 items\]. Each Item is measured on a 7-point scale, with scores ranging for IR from 5 to 35, LF from 3 to 21, GC from 3 to 21, HC from 5 to 35, IDD from 6 to 42. Lower scores reflect better outcomes. LS mean was calculated using generalized linear model with the analysis variable as outcome, and the baseline of analysis variable as covariate. ITSQ was not evaluated at Week 0. For this outcome, Week 4 was considered as baseline.
Time frame: Baseline (Week 4), Week 24
Population: All participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Glargine | Change From Week 4 in Insulin Treatment Satisfaction Questionnaire (ITSQ) | ITSQ GC Score | -0.2 score on a scale | Standard Error 0.05 |
| Insulin Glargine | Change From Week 4 in Insulin Treatment Satisfaction Questionnaire (ITSQ) | ITSQ IR Score | -0.3 score on a scale | Standard Error 0.04 |
| Insulin Glargine | Change From Week 4 in Insulin Treatment Satisfaction Questionnaire (ITSQ) | ITSQ LF Score | -0.3 score on a scale | Standard Error 0.05 |
| Insulin Glargine | Change From Week 4 in Insulin Treatment Satisfaction Questionnaire (ITSQ) | ITSQ HC Score | -0.3 score on a scale | Standard Error 0.05 |
| Insulin Glargine | Change From Week 4 in Insulin Treatment Satisfaction Questionnaire (ITSQ) | ITSQ IDD Score | -0.3 score on a scale | Standard Error 0.04 |