Diabetes Mellitus, Type 2
Conditions
Brief summary
The objective of the current study is to investigate the efficacy, safety and tolerability of linagliptin (5 mg / once daily) compared to placebo given for 24 weeks as add-on therapy to stable treatment in elderly patients with T2DM with insufficient glycaemic control
Interventions
DRUGlinagliptin
patients receive linagliptin 5 mg tablets once daily
DRUGplacebo
patients receive placebo matching linagliptin 5 mg once daily
Sponsors
Eli Lilly and Company
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
70 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Type 2 diabetes mellitus 2. HbA1c \>= 7.0% 3. Age \>= 70 years 4. Signed and dated written informed consent
Exclusion criteria
1. Myocardial infarction, stroke or TIA within 3 months prior to informed consent 2. Impaired hepatic function 3. Treatment with glitazones, GLP-1 analogues, DPP-4 inhibitors or rapid acting or pre-mixed insulins 4. Treatment with anti-obesity drugs
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| HbA1c Change From Baseline to Week 24 | Baseline and week 24 | HbA1c is measured as a percentage. Thus, this change from baseline reflects the Week 24 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for baseline HbA1c and prior use of insulin. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| HbA1c Change From Baseline to Week 12 | Baseline and week 12 | HbA1c is measured as a percentage. Thus, this change from baseline reflects the Week 12 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for baseline HbA1c and prior use of insulin. |
| HbA1c Change From Baseline to Week 18 | Baseline and week 18 | HbA1c is measured as a percentage. Thus, this change from baseline reflects the Week 18 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for baseline HbA1c and prior use of insulin. |
| FPG Change From Baseline to Week 24 | Baseline and week 24 | This change from baseline reflects the Week 24 FPG minus the baseline FPG. Means are treatment-adjusted for baseline HbA1c, baseline FPG and prior use of insulin. |
| FPG Change From Baseline to Week 6 | Baseline and week 6 | This change from baseline reflects the Week 6 FPG minus the baseline FPG. Means are treatment-adjusted for baseline HbA1c, baseline FPG and prior use of insulin, week repeated within patient and week by treatment interaction. |
| HbA1c Change From Baseline to Week 6 | Baseline and week 6 | HbA1c is measured as a percentage. Thus, this change from baseline reflects the Week 6 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for baseline HbA1c and prior use of insulin. |
| FPG Change From Baseline to Week 18 | Baseline and week 18 | This change from baseline reflects the Week 18 FPG minus the baseline FPG. Means are treatment-adjusted for baseline HbA1c, baseline FPG and prior use of insulin, week repeated within patient and week by treatment interaction. |
| Percentage of Patients With HbA1c <7.0% at Week 24 | Baseline and week 24 | The percentage of patients with an HbA1c value below 7% at week 24 was calculated for each treatment arm. If a patient did not have an HbA1c value at week 24 they were considered a failure, so HbA1c above 7%. Only patients with baseline HbA1c \>= 7% |
| Percentage of Patients Who Have a HbA1c Lowering by at Least 0.5% at Week 24 | Baseline and week 24 | The percentage of patients with an HbA1c reduction of ≥0.5% at week 24 from baseline was calculated for each treatment arm. If a patient did not have an HbA1c value at week 24 they were considered a failure, so HbA1c reduction less than 0.5% |
| Number of Patients With Rescue Therapy | week 24 | The use of rescue therapy was planned for patients failing to achieve preset criteria based on glucose levels during the randomised treatment period of the trial |
| FPG Change From Baseline to Week 12 | Baseline and week 12 | This change from baseline reflects the Week 12 FPG minus the baseline FPG. Means are treatment-adjusted for baseline HbA1c, baseline FPG and prior use of insulin, week repeated within patient and week by treatment interaction. |
Countries
Australia, Canada, Denmark, Netherlands, Sweden
Participant flow
Pre-assignment details
A total of 241 patients were randomised in a 2:1 ratio to receive treatment with linagliptin 5mg (n=162) or placebo (n=79). All randomised patients were treated.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Patients randomized to receive treatment with matching placebo | 79 |
| Linagliptin 5 mg Patients randomized to receive treatment with Linagliptin 5mg | 162 |
| Total | 241 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 8 |
| Overall Study | Protocol Violation | 3 | 7 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Placebo | Linagliptin 5 mg | Total |
|---|---|---|---|
| Age, Continuous | 74.9 Years STANDARD_DEVIATION 4.2 | 74.9 Years STANDARD_DEVIATION 4.4 | 74.9 Years STANDARD_DEVIATION 4.3 |
| Body mass index (BMI) continuous | 29.80 kg/m^2 STANDARD_DEVIATION 4.54 | 29.60 kg/m^2 STANDARD_DEVIATION 4.74 | 29.67 kg/m^2 STANDARD_DEVIATION 4.67 |
| Fasting Plasma Glucose (FPG) | 144.1 mg/dL STANDARD_DEVIATION 29.6 | 152.7 mg/dL STANDARD_DEVIATION 28.7 | 149.9 mg/dL STANDARD_DEVIATION 29.2 |
| Glycosylated Hemoglobin A1 (HbA1c) | 7.70 Percent STANDARD_DEVIATION 0.7 | 7.82 Percent STANDARD_DEVIATION 0.78 | 7.78 Percent STANDARD_DEVIATION 0.76 |
| Sex: Female, Male Female | 30 Participants | 46 Participants | 76 Participants |
| Sex: Female, Male Male | 49 Participants | 116 Participants | 165 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 37 / 79 | 70 / 162 |
| serious Total, serious adverse events | 5 / 79 | 14 / 162 |
Outcome results
Primary
HbA1c Change From Baseline to Week 24
HbA1c is measured as a percentage. Thus, this change from baseline reflects the Week 24 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for baseline HbA1c and prior use of insulin.
Time frame: Baseline and week 24
Population: FAS consisting of all randomised patients who were treated with at least one dose of study drug, had a baseline, and at least 1 on-treatment HbA1c measurement. Last observation carried forward (LOCF) was used as the imputation rule.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | HbA1c Change From Baseline to Week 24 | 0.04 Percent | Standard Error 0.07 |
| Linagliptin 5 mg | HbA1c Change From Baseline to Week 24 | -0.61 Percent | Standard Error 0.06 |
p-value: <0.000195% CI: [-0.81, -0.48]ANCOVA
Secondary
FPG Change From Baseline to Week 12
This change from baseline reflects the Week 12 FPG minus the baseline FPG. Means are treatment-adjusted for baseline HbA1c, baseline FPG and prior use of insulin, week repeated within patient and week by treatment interaction.
Time frame: Baseline and week 12
Population: FAS (OC)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | FPG Change From Baseline to Week 12 | 6.8 mg/dL | Standard Error 2.9 |
| Linagliptin 5 mg | FPG Change From Baseline to Week 12 | -14.7 mg/dL | Standard Error 2.1 |
p-value: <0.000195% CI: [-28.1, -14.8]Mixed Models Analysis
Secondary
FPG Change From Baseline to Week 18
This change from baseline reflects the Week 18 FPG minus the baseline FPG. Means are treatment-adjusted for baseline HbA1c, baseline FPG and prior use of insulin, week repeated within patient and week by treatment interaction.
Time frame: Baseline and week 18
Population: FAS (OC)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | FPG Change From Baseline to Week 18 | 9.6 mg/dL | Standard Error 3.6 |
| Linagliptin 5 mg | FPG Change From Baseline to Week 18 | -12.0 mg/dL | Standard Error 2.5 |
p-value: <0.000195% CI: [-29.8, -13.4]Mixed Models Analysis
Secondary
FPG Change From Baseline to Week 24
This change from baseline reflects the Week 24 FPG minus the baseline FPG. Means are treatment-adjusted for baseline HbA1c, baseline FPG and prior use of insulin.
Time frame: Baseline and week 24
Population: FAS (LOCF)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | FPG Change From Baseline to Week 24 | 10.1 mg/dL | Standard Error 4.3 |
| Linagliptin 5 mg | FPG Change From Baseline to Week 24 | -10.6 mg/dL | Standard Error 3.2 |
p-value: <0.000195% CI: [-30.2, -11.2]ANCOVA
Secondary
FPG Change From Baseline to Week 6
This change from baseline reflects the Week 6 FPG minus the baseline FPG. Means are treatment-adjusted for baseline HbA1c, baseline FPG and prior use of insulin, week repeated within patient and week by treatment interaction.
Time frame: Baseline and week 6
Population: FAS Observed cases (OC)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | FPG Change From Baseline to Week 6 | 4.6 mg/dL | Standard Error 2.7 |
| Linagliptin 5 mg | FPG Change From Baseline to Week 6 | -14.1 mg/dL | Standard Error 2 |
p-value: <0.000195% CI: [-24.7, -12.6]Mixed Models Analysis
Secondary
HbA1c Change From Baseline to Week 12
HbA1c is measured as a percentage. Thus, this change from baseline reflects the Week 12 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for baseline HbA1c and prior use of insulin.
Time frame: Baseline and week 12
Population: FAS (LOCF)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | HbA1c Change From Baseline to Week 12 | -0.03 Percent | Standard Error 0.06 |
| Linagliptin 5 mg | HbA1c Change From Baseline to Week 12 | -0.60 Percent | Standard Error 0.05 |
p-value: <0.000195% CI: [-0.71, -0.43]ANCOVA
Secondary
HbA1c Change From Baseline to Week 18
HbA1c is measured as a percentage. Thus, this change from baseline reflects the Week 18 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for baseline HbA1c and prior use of insulin.
Time frame: Baseline and week 18
Population: FAS (LOCF)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | HbA1c Change From Baseline to Week 18 | 0.04 Percent | Standard Error 0.07 |
| Linagliptin 5 mg | HbA1c Change From Baseline to Week 18 | -0.58 Percent | Standard Error 0.05 |
p-value: <0.000195% CI: [-0.77, -0.47]ANCOVA
Secondary
HbA1c Change From Baseline to Week 6
HbA1c is measured as a percentage. Thus, this change from baseline reflects the Week 6 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for baseline HbA1c and prior use of insulin.
Time frame: Baseline and week 6
Population: FAS (LOCF)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | HbA1c Change From Baseline to Week 6 | -0.07 Percent | Standard Error 0.05 |
| Linagliptin 5 mg | HbA1c Change From Baseline to Week 6 | -0.42 Percent | Standard Error 0.03 |
p-value: <0.000195% CI: [-0.45, -0.24]ANCOVA
Secondary
Number of Patients With Rescue Therapy
The use of rescue therapy was planned for patients failing to achieve preset criteria based on glucose levels during the randomised treatment period of the trial
Time frame: week 24
Population: FAS (OC)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Patients With Rescue Therapy | 11 Number of patients |
| Linagliptin 5 mg | Number of Patients With Rescue Therapy | 7 Number of patients |
Comparison: Lina 5 mg qd vs Placebop-value: 0.004895% CI: [0.073, 0.625]Regression, Logistic
Secondary
Percentage of Patients Who Have a HbA1c Lowering by at Least 0.5% at Week 24
The percentage of patients with an HbA1c reduction of ≥0.5% at week 24 from baseline was calculated for each treatment arm. If a patient did not have an HbA1c value at week 24 they were considered a failure, so HbA1c reduction less than 0.5%
Time frame: Baseline and week 24
Population: FAS (NCF)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Patients Who Have a HbA1c Lowering by at Least 0.5% at Week 24 | 12.8 percentage of patients |
| Linagliptin 5 mg | Percentage of Patients Who Have a HbA1c Lowering by at Least 0.5% at Week 24 | 54.4 percentage of patients |
Secondary
Percentage of Patients With HbA1c <7.0% at Week 24
The percentage of patients with an HbA1c value below 7% at week 24 was calculated for each treatment arm. If a patient did not have an HbA1c value at week 24 they were considered a failure, so HbA1c above 7%. Only patients with baseline HbA1c \>= 7%
Time frame: Baseline and week 24
Population: FAS with baseline HbA1c \>=7% and non-completers considered as failure imputation (NCF)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Patients With HbA1c <7.0% at Week 24 | 8.3 percentage of patients |
| Linagliptin 5 mg | Percentage of Patients With HbA1c <7.0% at Week 24 | 38.9 percentage of patients |
p-value: <0.000195% CI: [3.321, 20.837]Regression, Logistic
Secondary
Percentage of Patients With HbA1c <7.0% at Week 24
The percentage of patients with an HbA1c value below 7% at week 24 were calculated for each treatment arm. If a patient did not have an HbA1c value at week 24 they were considered a failure, so HbA1c above 7%.
Time frame: Baseline and week 24
Population: FAS (NCF)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Patients With HbA1c <7.0% at Week 24 | 11.5 percentage of patients |
| Linagliptin 5 mg | Percentage of Patients With HbA1c <7.0% at Week 24 | 41.9 percentage of patients |