Type 2 Diabetes Mellitus
Conditions
Brief summary
The reason for this study is to see if the study drug LY3209590 is safe and effective in participants with type 2 diabetes.
Interventions
DRUGLY3209590
Administered SC
DRUGInsulin Degludec
Administered SC
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Participants must have type 2 diabetes mellitus according to the World Health Organization (WHO) criteria treated with a stable dose of metformin in combination with a stable dose of Dipeptidyl Peptidase IV (DPPIV) inhibitor and/or a Sodium-glucose co-transporter-2 (SGLT2) inhibitor for at least 3 months prior to screening * Participants must have a HbA1c value of 7.0% to 9.5%, inclusive * Participants must have a body mass index (BMI) between 20 and 45 kilograms per meter squared (kg/m²), inclusive
Exclusion criteria
* Have type 1 diabetes mellitus or latent autoimmune diabetes * Have any episodes of severe hypoglycemia and/or hypoglycemia unawareness within the 6 months prior to screening * Have any of the following cardiovascular (CV) conditions: acute myocardial infarction, New York Heart Association Class III or IV heart failure, or cerebrovascular accident (stroke) * Have acute or chronic hepatitis, or obvious clinical signs or symptoms of any other liver disease * Have an estimated glomerular filtration rate (eGFR) \<30 milliliters/minute/1.73 m² * Have active or untreated cancer * Are receiving chronic (\>14 days) systemic glucocorticoid therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Hemoglobin A1c (HbA1c) | Baseline, Week 26 | HbA1c is the glycosylated fraction of haemoglobin A. It is measured to identify average blood glucose concentration over prolonged periods of time. Least squares (LS) mean change from baseline was analysed by mixed model repeated measures (MMRM) model with treatment, country, Dipeptidyl peptidase IV (DPPIV) (yes/no), Sodium-glucose Cotransporter-2 (SGLT2) (yes/no), baseline body mass index (BMI) \[\<30, \>=30\]), visit, and treatment by visit interaction as fixed effects and the baseline HbA1c as a covariate. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Fasting Serum Glucose | Baseline, Week 26 | LS mean change from baseline was analysed by MMRM model with treatment, country, DPPIV (yes/no), SGLT2 (yes/no), baseline BMI \[\<30, \>=30\]), visit, and treatment by visit interaction as fixed effects and the baseline fasting serum glucose as a covariate. |
| Rate of Documented Hypoglycemia | Baseline through Week 26 | Documented hypoglycemia is defined as any time a participant reports a self-monitoring blood glucose \<54 mg/dL (3.0 millimole per liter (mmol/L)). Rate of documented hypoglycemia per year during defined period is calculated by the number of documented hypoglycemia events within the period divided by the number of days participant at risk within the period\*365.25 days. |
| Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of LY3209590 | Week 26 | AUC of LY3209590 was calculated for individual participants using the participants' Week 26 LY3209590 dose amount and estimated clearance value. |
Countries
Argentina, Germany, Poland, Puerto Rico, United States
Participant flow
Recruitment details
The study was initially designed as 3 arms: LY3209590 Algorithm 1 (Paper), LY3209590 Algorithm 2 (Digital), and Insulin Degludec. However, it was amended to terminate the LY3209590 Algorithm 2 (Digital) arm during early enrollment phase due to technical issues with data entry. Thus, this arm was excluded from the outcome measure analyses, but safety data was analysed and reported.
Participants by arm
| Arm | Count |
|---|---|
| LY3209590 Algorithm 1 (Paper) Algorithm 1 is a paper-based algorithm where dose adjustments were manually determined by the investigator based on fasting glucose and hypoglycemia data. LY3209590 was provided in a 20 mg vial of reconstitutable lyophilized powder. Participants received individualized LY3209590 loading dose based on the baseline median fasting glucose and body weight by SC injection on day 1 followed by weekly adjustments for the first 12 weeks, then every 4 weeks, of a 26-week treatment period, to achieve target fasting glucose of \<=100 mg/dL. | 129 |
| Insulin Degludec Insulin degludec was provided as 100 U/mL in a prefilled pen. Participants received individually adjusted doses once daily by SC injection with a starting dose of 10 units, during the 26-week treatment period, to achieve target fasting blood glucose of \<=100 mg/dL. | 135 |
| LY3209590 Algorithm 2 (Digital) Algorithm 2 is a computer-based algorithm to determine dose adjustments. LY3209590 was provided in a 20 mg vial of reconstitutable lyophilized powder. Participants received individualized LY3209590 loading dose based on the baseline median fasting glucose and body weight by SC injection on day 1 followed by weekly adjustments for the first 12 weeks, then every 4 weeks, of a 26-week treatment period, to achieve target fasting glucose of \<=100 mg/dL. | 14 |
| Total | 278 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 | 0 |
| Overall Study | Death | 0 | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 3 | 0 |
| Overall Study | Physician Decision | 0 | 1 | 0 |
| Overall Study | Protocol Violation | 2 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 6 | 9 | 0 |
Baseline characteristics
| Characteristic | Total | LY3209590 Algorithm 2 (Digital) | Insulin Degludec | LY3209590 Algorithm 1 (Paper) |
|---|---|---|---|---|
| Age, Continuous | 58.3 years STANDARD_DEVIATION 9.5 | 56.3 years STANDARD_DEVIATION 8.8 | 59.4 years STANDARD_DEVIATION 9.1 | 57.4 years STANDARD_DEVIATION 9.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 128 Participants | 8 Participants | 59 Participants | 61 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 150 Participants | 6 Participants | 76 Participants | 68 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Haemoglobin A1c (HbA1c) | 8.02 Percentage of HbA1c STANDARD_DEVIATION 0.77 | 8.38 Percentage of HbA1c STANDARD_DEVIATION 0.83 | 7.95 Percentage of HbA1c STANDARD_DEVIATION 0.75 | 8.05 Percentage of HbA1c STANDARD_DEVIATION 0.77 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 19 Participants | 1 Participants | 14 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 254 Participants | 12 Participants | 119 Participants | 123 Participants |
| Region of Enrollment Argentina | 56 Participants | 0 Participants | 27 Participants | 29 Participants |
| Region of Enrollment Germany | 39 Participants | 0 Participants | 21 Participants | 18 Participants |
| Region of Enrollment Poland | 42 Participants | 0 Participants | 22 Participants | 20 Participants |
| Region of Enrollment Puerto Rico | 15 Participants | 2 Participants | 4 Participants | 9 Participants |
| Region of Enrollment United States | 126 Participants | 12 Participants | 61 Participants | 53 Participants |
| Sex: Female, Male Female | 126 Participants | 9 Participants | 59 Participants | 58 Participants |
| Sex: Female, Male Male | 152 Participants | 5 Participants | 76 Participants | 71 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 129 | 1 / 135 | 0 / 14 |
| other Total, other adverse events | 18 / 129 | 19 / 135 | 8 / 14 |
| serious Total, serious adverse events | 6 / 129 | 4 / 135 | 1 / 14 |
Outcome results
Primary
Change From Baseline in Hemoglobin A1c (HbA1c)
HbA1c is the glycosylated fraction of haemoglobin A. It is measured to identify average blood glucose concentration over prolonged periods of time. Least squares (LS) mean change from baseline was analysed by mixed model repeated measures (MMRM) model with treatment, country, Dipeptidyl peptidase IV (DPPIV) (yes/no), Sodium-glucose Cotransporter-2 (SGLT2) (yes/no), baseline body mass index (BMI) \[\<30, \>=30\]), visit, and treatment by visit interaction as fixed effects and the baseline HbA1c as a covariate.
Time frame: Baseline, Week 26
Population: All participants randomized to either LY3209590 Algorithm 1 (Paper) or Insulin degludec, received at least one dose of study drug and had baseline, post-baseline HbA1c data prior to treatment discontinuation.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| LY3209590 Algorithm 1 (Paper) | Change From Baseline in Hemoglobin A1c (HbA1c) | -1.20 Percentage of HbA1c | Standard Error 0.076 |
| Insulin Degludec | Change From Baseline in Hemoglobin A1c (HbA1c) | -1.26 Percentage of HbA1c | Standard Error 0.075 |
90% CI: [-0.11, 0.24]
Secondary
Change From Baseline in Fasting Serum Glucose
LS mean change from baseline was analysed by MMRM model with treatment, country, DPPIV (yes/no), SGLT2 (yes/no), baseline BMI \[\<30, \>=30\]), visit, and treatment by visit interaction as fixed effects and the baseline fasting serum glucose as a covariate.
Time frame: Baseline, Week 26
Population: All participants randomized to either LY3209590 Algorithm 1 (Paper) or Insulin degludec, received at least one dose of study drug and had baseline, post-baseline fasting serum glucose data prior to treatment discontinuation.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| LY3209590 Algorithm 1 (Paper) | Change From Baseline in Fasting Serum Glucose | -50.7 milligrams per deciliter (mg/dL) | Standard Error 2.81 |
| Insulin Degludec | Change From Baseline in Fasting Serum Glucose | -58.7 milligrams per deciliter (mg/dL) | Standard Error 2.83 |
Secondary
Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of LY3209590
AUC of LY3209590 was calculated for individual participants using the participants' Week 26 LY3209590 dose amount and estimated clearance value.
Time frame: Week 26
Population: All participants randomized to LY3209590 Algorithm 1 (Paper), received at least one dose of study drug and had evaluable PK data at week 26.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LY3209590 Algorithm 1 (Paper) | Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of LY3209590 | 5890 Nanomole*hour per Liter (nmol*hr/L) | Geometric Coefficient of Variation 66 |
Secondary
Rate of Documented Hypoglycemia
Documented hypoglycemia is defined as any time a participant reports a self-monitoring blood glucose \<54 mg/dL (3.0 millimole per liter (mmol/L)). Rate of documented hypoglycemia per year during defined period is calculated by the number of documented hypoglycemia events within the period divided by the number of days participant at risk within the period\*365.25 days.
Time frame: Baseline through Week 26
Population: All participants randomized to either LY3209590 Algorithm 1 (Paper) or Insulin degludec, received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LY3209590 Algorithm 1 (Paper) | Rate of Documented Hypoglycemia | 0.21 Events per participant per year |
| Insulin Degludec | Rate of Documented Hypoglycemia | 0.15 Events per participant per year |