Diabetes Mellitus, Type 2
Conditions
Keywords
Adult, GLP-1
Brief summary
The main purpose of this study is to evaluate safety of dulaglutide in participants with type 2 diabetes mellitus in India.
Interventions
DRUGDulaglutide
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 No maximum
Healthy volunteers
No
Inclusion criteria
* Have a diagnosis of type 2 diabetes mellitus (T2DM) of at least 1-year duration currently treated with stable doses of oral antihyperglycemic medications with or without stable doses of basal or premix insulin for the last 3 months prior to screening * Have hemoglobin A1c (HbA1c) greater than or equal to (≥) 7.5 percent (%) and less than or equal to (≤) 11.5%, both inclusive, at screening * Have body mass index (BMI) ≥ 23 kilogram/square meter (kg/m²)
Exclusion criteria
* A diagnosis of type 1 diabetes mellitus (T1DM) or latent autoimmune diabetes, or specific type of diabetes other than T2DM * Been treated with antihyperglycemic medication like glucagon-like peptide receptor agonists (GLP-1 RA) or have a prior history of any contraindication to GLP-1 RA therapy within 3 months prior to screening or estimated glomerular filtration rate (eGFR) \<15 milliliter/minute (ml/min)/1.73 square meter (m²) * Participants have known hypersensitivity or allergy to dulaglutide or its excipients * Participants are on systemic steroids for any period of more than 14 days * Participants have severe gastrointestinal (GI) disease, including severe gastroparesis * Participants have an active or untreated malignancy, except for successfully treated basal or squamous cell carcinoma
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With One or More Adverse Events (AEs) - Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Deaths | Baseline through Follow-up (up to 28 weeks) | * An AE was any untoward medical occurrence in a participant who was administered an investigational product that did not necessarily have a causal relationship with the treatment. A TEAE was defined as an AE that occurred post-dose or was present prior to dosing and became more severe post-dose. * An SAE was any AE from the study that resulted in one of the following: death, initial or prolonged inpatient hospitalization, a life-threatening experience (i.e., immediate risk of dying), persistent or significant disability/incapacity, congenital anomaly/birth defect, or important medical events that might not have been immediately life-threatening or resulted in death or hospitalization but might have jeopardized the participant or required intervention to prevent one of the other outcomes listed in the definition above. * A summary of SAEs and other non-serious AEs, regardless of causality, is located in the reported Adverse Events section of this record. |
| Number of Participants With One or More Hypoglycemic Events, Including Severe Hypoglycemic Events. | Baseline through Follow-up (up to 28 weeks) | Hypoglycemia events were defined as those with blood glucose (BG) levels less than (\<) 70 milligrams per deciliter (mg/dL). Severe hypoglycemia events were defined as those with severe cognitive impairment requiring the assistance of another person to actively administer carbohydrates, glucagon, or other resuscitative actions. These events could be associated with sufficient neuroglycopenia to induce seizures or coma. The total number of participants who experienced hypoglycemia events, including severe hypoglycemia, was summarized cumulatively. |
| Percentage of Participants Reporting AEs and SAEs From Baseline to Week 24 | Baseline through Week 24 | The percentage of participants who reported AEs and SAEs was calculated by dividing the total number of affected participants by the number of participants analyzed, then multiplying by 100. A summary of SAEs and other non-serious AEs, regardless of causality, is located in the reported Adverse Events section of this record. |
| Number of Participants With One or More Gastrointestinal (GI) AEs From Baseline to Week 24 | Baseline through Week 24 | The number of participants who experienced at least one or more GI AEs of nausea, vomiting, and diarrhoea were summarized cumulatively. A summary of SAEs and other non-serious AEs, regardless of causality, is located in the reported Adverse Events section of this record. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in HbA1c From Baseline to Week 24 | Baseline, Week 24 | HbA1c is the glycosylated fraction of hemoglobin A. It is measured to identify average plasma glucose concentration over prolonged periods of time. The mean change in HbA1c levels was calculated using descriptive analysis, with baseline HbA1c as a covariate. Missing endpoints were addressed using the last observation carried forward (LOCF) method. |
Countries
India
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dulaglutide * Participants received QW dulaglutide SC injections for 24 weeks, starting with either 1.5 mg as combination therapy or 0.75 mg as combination therapy or monotherapy (at the discretion of the investigator).
* For participants reporting GI AEs after starting the 1.5 mg dulaglutide dose, the investigator reduced the dose to 0.75 mg for 2 to 3 weeks. Thereafter, the 1.5 mg dose was reintroduced. | 189 |
| Total | 189 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 5 |
| Overall Study | Lost to Follow-up | 4 |
| Overall Study | Migration from the Study Site Such That Follow Up Visits are not Possible | 3 |
| Overall Study | Participant had low absolute neutrophil count value | 1 |
| Overall Study | Participant was suffering from anaemia | 1 |
| Overall Study | Withdrawal by Subject | 13 |
Baseline characteristics
| Characteristic | Dulaglutide |
|---|---|
| Age, Continuous | 54.1 years STANDARD_DEVIATION 10.45 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 189 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 189 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 | 189 Participants |
| Sex: Female, Male Female | 102 Participants |
| Sex: Female, Male Male | 87 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 165 | 0 / 21 | 0 / 14 |
| other Total, other adverse events | 100 / 165 | 8 / 21 | 6 / 14 |
| serious Total, serious adverse events | 1 / 165 | 0 / 21 | 0 / 14 |
Outcome results
Primary
Number of Participants With One or More Adverse Events (AEs) - Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Deaths
* An AE was any untoward medical occurrence in a participant who was administered an investigational product that did not necessarily have a causal relationship with the treatment. A TEAE was defined as an AE that occurred post-dose or was present prior to dosing and became more severe post-dose. * An SAE was any AE from the study that resulted in one of the following: death, initial or prolonged inpatient hospitalization, a life-threatening experience (i.e., immediate risk of dying), persistent or significant disability/incapacity, congenital anomaly/birth defect, or important medical events that might not have been immediately life-threatening or resulted in death or hospitalization but might have jeopardized the participant or required intervention to prevent one of the other outcomes listed in the definition above. * A summary of SAEs and other non-serious AEs, regardless of causality, is located in the reported Adverse Events section of this record.
Time frame: Baseline through Follow-up (up to 28 weeks)
Population: All participants who received at least one dulaglutide dose and had at least one HbA1c measurement post-study treatment. As prespecified in the statistical analysis plan, the primary and secondary outcomes were planned to be analyzed and reported by dose level only if the proportion in each arm was more than 20 percent (%). However, the percentage in the 1.5 mg only or 0.75 mg only dulaglutide arm was lower than 20 %. Hence, outcomes are reported for the overall dulaglutide treatment group.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dulaglutide | Number of Participants With One or More Adverse Events (AEs) - Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Deaths | TEAEs | 106 Participants |
| Dulaglutide | Number of Participants With One or More Adverse Events (AEs) - Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Deaths | SAEs | 1 Participants |
| Dulaglutide | Number of Participants With One or More Adverse Events (AEs) - Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Deaths | Deaths | 0 Participants |
Primary
Number of Participants With One or More Gastrointestinal (GI) AEs From Baseline to Week 24
The number of participants who experienced at least one or more GI AEs of nausea, vomiting, and diarrhoea were summarized cumulatively. A summary of SAEs and other non-serious AEs, regardless of causality, is located in the reported Adverse Events section of this record.
Time frame: Baseline through Week 24
Population: All participants who received at least one dulaglutide dose and had at least one HbA1c measurement post-study treatment. As prespecified in the statistical analysis plan, the primary and secondary outcomes were planned to be analyzed and reported by dose level only if the proportion in each arm was more than 20%. However, the percentage in the 1.5 mg only or 0.75 mg only dulaglutide arm was lower than 20%. Hence, outcomes are reported for the overall dulaglutide treatment group.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dulaglutide | Number of Participants With One or More Gastrointestinal (GI) AEs From Baseline to Week 24 | 48 Participants |
Primary
Number of Participants With One or More Hypoglycemic Events, Including Severe Hypoglycemic Events.
Hypoglycemia events were defined as those with blood glucose (BG) levels less than (\<) 70 milligrams per deciliter (mg/dL). Severe hypoglycemia events were defined as those with severe cognitive impairment requiring the assistance of another person to actively administer carbohydrates, glucagon, or other resuscitative actions. These events could be associated with sufficient neuroglycopenia to induce seizures or coma. The total number of participants who experienced hypoglycemia events, including severe hypoglycemia, was summarized cumulatively.
Time frame: Baseline through Follow-up (up to 28 weeks)
Population: All participants who received at least one dulaglutide dose and had at least one HbA1c measurement post-study treatment. As prespecified in the statistical analysis plan, the primary and secondary outcomes were planned to be analyzed and reported by dose level only if the proportion in each arm was more than 20%. However, the percentage in the 1.5 mg only or 0.75 mg only dulaglutide arm was lower than 20%. Hence, outcomes are reported for the overall dulaglutide treatment group.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dulaglutide | Number of Participants With One or More Hypoglycemic Events, Including Severe Hypoglycemic Events. | 13 Participants |
Primary
Percentage of Participants Reporting AEs and SAEs From Baseline to Week 24
The percentage of participants who reported AEs and SAEs was calculated by dividing the total number of affected participants by the number of participants analyzed, then multiplying by 100. A summary of SAEs and other non-serious AEs, regardless of causality, is located in the reported Adverse Events section of this record.
Time frame: Baseline through Week 24
Population: All participants who received at least one dulaglutide dose and had at least one HbA1c measurement post-study treatment. As prespecified in the statistical analysis plan, the primary and secondary outcomes were planned to be analyzed and reported by dose level only if the proportion in each arm was more than 20%. However, the percentage in the 1.5 mg only or 0.75 mg only dulaglutide arm was lower than 20%. Hence, outcomes are reported for the overall dulaglutide treatment group.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dulaglutide | Percentage of Participants Reporting AEs and SAEs From Baseline to Week 24 | AEs | 51.9 percentage of participants |
| Dulaglutide | Percentage of Participants Reporting AEs and SAEs From Baseline to Week 24 | SAEs | 0.5 percentage of participants |
Secondary
Mean Change in HbA1c From Baseline to Week 24
HbA1c is the glycosylated fraction of hemoglobin A. It is measured to identify average plasma glucose concentration over prolonged periods of time. The mean change in HbA1c levels was calculated using descriptive analysis, with baseline HbA1c as a covariate. Missing endpoints were addressed using the last observation carried forward (LOCF) method.
Time frame: Baseline, Week 24
Population: All participants who received at least one dulaglutide dose and had at least one HbA1c measurement post-study treatment. As prespecified in the statistical analysis plan, the primary and secondary outcomes were planned to be analyzed and reported by dose level only if the proportion in each arm was more than 20%. However, the percentage in the 1.5 mg only or 0.75 mg only dulaglutide arm was lower than 20%. Hence, outcomes are reported for the overall dulaglutide treatment group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dulaglutide | Mean Change in HbA1c From Baseline to Week 24 | -1.41 Percentage of HbA1c | Standard Deviation 1.422 |