Trial Outcomes & Findings for Treatment of Type 2 Diabetes With Linagliptin 2.5 mg Bid + Metformin 500 or 1000 mg Bid and Metformin 1000 mg Bid (NCT NCT00915772)
NCT ID: NCT00915772
Last Updated: 2014-05-14
Results Overview
This includes any AEs detected during routine physical examination and electrocardiogram (ECG) procedures.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
567 participants
Primary outcome timeframe
54 weeks
Results posted on
2014-05-14
Participant Flow
In this study, 567 patients were entered and randomised, but only 566 were treated. Therefore the treated set (TS) comprises 566 patients.
Participant milestones
| Measure |
M1000
Metformin 1000mg monotherapy twice daily
|
L2.5+M500
Linagliptin 2.5mg and metformin 500mg twice daily
|
L2.5+M1000
Linagliptin 2.5mg and metformin 1000mg twice daily
|
|---|---|---|---|
|
Overall Study
STARTED
|
170
|
225
|
171
|
|
Overall Study
COMPLETED
|
134
|
179
|
142
|
|
Overall Study
NOT COMPLETED
|
36
|
46
|
29
|
Reasons for withdrawal
| Measure |
M1000
Metformin 1000mg monotherapy twice daily
|
L2.5+M500
Linagliptin 2.5mg and metformin 500mg twice daily
|
L2.5+M1000
Linagliptin 2.5mg and metformin 1000mg twice daily
|
|---|---|---|---|
|
Overall Study
Adverse Event
|
12
|
13
|
11
|
|
Overall Study
Protocol Violation
|
4
|
1
|
2
|
|
Overall Study
Lost to Follow-up
|
1
|
2
|
2
|
|
Overall Study
Lack of Efficacy
|
9
|
15
|
3
|
|
Overall Study
Refused to continue trial medication
|
6
|
8
|
4
|
|
Overall Study
Any other reason
|
4
|
7
|
7
|
Baseline Characteristics
Treatment of Type 2 Diabetes With Linagliptin 2.5 mg Bid + Metformin 500 or 1000 mg Bid and Metformin 1000 mg Bid
Baseline characteristics by cohort
| Measure |
M1000
n=170 Participants
Metformin 1000mg monotherapy twice daily
|
L2.5+M500
n=225 Participants
Linagliptin 2.5mg and metformin 500mg twice daily
|
L2.5+M1000
n=171 Participants
Linagliptin 2.5mg and metformin 1000mg twice daily
|
Total
n=566 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
55.6 Years
STANDARD_DEVIATION 10.7 • n=93 Participants
|
56.0 Years
STANDARD_DEVIATION 10.7 • n=4 Participants
|
55.7 Years
STANDARD_DEVIATION 10.8 • n=27 Participants
|
55.8 Years
STANDARD_DEVIATION 10.7 • n=483 Participants
|
|
Sex: Female, Male
Female
|
77 Participants
n=93 Participants
|
105 Participants
n=4 Participants
|
74 Participants
n=27 Participants
|
256 Participants
n=483 Participants
|
|
Sex: Female, Male
Male
|
93 Participants
n=93 Participants
|
120 Participants
n=4 Participants
|
97 Participants
n=27 Participants
|
310 Participants
n=483 Participants
|
|
Body Mass Index (BMI) continuous
|
29.33 kg/m2
STANDARD_DEVIATION 5.22 • n=93 Participants
|
29.06 kg/m2
STANDARD_DEVIATION 4.95 • n=4 Participants
|
28.64 kg/m2
STANDARD_DEVIATION 4.79 • n=27 Participants
|
29.01 kg/m2
STANDARD_DEVIATION 4.98 • n=483 Participants
|
|
Baseline weight
|
81.09 kg
STANDARD_DEVIATION 18.92 • n=93 Participants
|
79.17 kg
STANDARD_DEVIATION 18.75 • n=4 Participants
|
78.62 kg
STANDARD_DEVIATION 16.86 • n=27 Participants
|
79.58 kg
STANDARD_DEVIATION 18.25 • n=483 Participants
|
|
Baseline Glycosylated haemoglobin (HbA1c) at baseline
|
7.48 percent
STANDARD_DEVIATION 0.99 • n=93 Participants
|
7.64 percent
STANDARD_DEVIATION 1.04 • n=4 Participants
|
7.35 percent
STANDARD_DEVIATION 1.12 • n=27 Participants
|
7.50 percent
STANDARD_DEVIATION 1.06 • n=483 Participants
|
|
Fasting plasma glucose (FPG) at baseline
|
156.585 mg/dL
STANDARD_DEVIATION 39.194 • n=93 Participants
|
167.088 mg/dL
STANDARD_DEVIATION 44.633 • n=4 Participants
|
153.721 mg/dL
STANDARD_DEVIATION 37.128 • n=27 Participants
|
159.868 mg/dL
STANDARD_DEVIATION 41.206 • n=483 Participants
|
PRIMARY outcome
Timeframe: 54 weeksPopulation: Treated Set (TS): all screened patients who were documented to have taken at lease 1 dose of study drug.
This includes any AEs detected during routine physical examination and electrocardiogram (ECG) procedures.
Outcome measures
| Measure |
M1000
n=170 Participants
Metformin 1000mg monotherapy twice daily
|
L2.5+M500
n=225 Participants
Linagliptin 2.5mg and metformin 500mg twice daily
|
L2.5+M1000
n=171 Participants
Linagliptin 2.5mg and metformin 1000mg twice daily
|
Post-treat
7 days follow-up period
|
|---|---|---|---|---|
|
Frequency of Patients With Adverse Events (AEs)
Patients with any AEs
|
124 participant
|
149 participant
|
132 participant
|
—
|
|
Frequency of Patients With Adverse Events (AEs)
Patients with severe AEs
|
4 participant
|
7 participant
|
5 participant
|
—
|
|
Frequency of Patients With Adverse Events (AEs)
Patients with withdrawal due to AEs (from AE page)
|
10 participant
|
11 participant
|
9 participant
|
—
|
PRIMARY outcome
Timeframe: 54 weeksPopulation: TS and observed cases (OC)
Baseline is defined as Visit 1 of 1218.52.
Outcome measures
| Measure |
M1000
n=164 Participants
Metformin 1000mg monotherapy twice daily
|
L2.5+M500
n=214 Participants
Linagliptin 2.5mg and metformin 500mg twice daily
|
L2.5+M1000
n=165 Participants
Linagliptin 2.5mg and metformin 1000mg twice daily
|
Post-treat
7 days follow-up period
|
|---|---|---|---|---|
|
Change From Baseline at Week 54 in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
DBP change from baseline
|
-0.3 mmHg
Standard Deviation 8.5
|
-0.1 mmHg
Standard Deviation 7.4
|
0.3 mmHg
Standard Deviation 8.8
|
—
|
|
Change From Baseline at Week 54 in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
SBP change from baseline
|
0.6 mmHg
Standard Deviation 12.2
|
-0.2 mmHg
Standard Deviation 13.2
|
2.2 mmHg
Standard Deviation 13.6
|
—
|
PRIMARY outcome
Timeframe: 54 weeksPopulation: TS and observed cases (OC)
Baseline is defined as Visit 1 of 1218.52.
Outcome measures
| Measure |
M1000
n=164 Participants
Metformin 1000mg monotherapy twice daily
|
L2.5+M500
n=214 Participants
Linagliptin 2.5mg and metformin 500mg twice daily
|
L2.5+M1000
n=164 Participants
Linagliptin 2.5mg and metformin 1000mg twice daily
|
Post-treat
7 days follow-up period
|
|---|---|---|---|---|
|
Change From Baseline at Week 54 in Pulse Rate
|
0.0 beats per minute (bpm)
Standard Deviation 7.7
|
0.6 beats per minute (bpm)
Standard Deviation 8.3
|
0.1 beats per minute (bpm)
Standard Deviation 8.3
|
—
|
PRIMARY outcome
Timeframe: 54 weeksPopulation: TS and observed cases (OC)
Outcome measures
| Measure |
M1000
n=168 Participants
Metformin 1000mg monotherapy twice daily
|
L2.5+M500
n=225 Participants
Linagliptin 2.5mg and metformin 500mg twice daily
|
L2.5+M1000
n=170 Participants
Linagliptin 2.5mg and metformin 1000mg twice daily
|
Post-treat
7 days follow-up period
|
|---|---|---|---|---|
|
Frequency of Patients With Possibly Clinically Significant Abnormal Laboratory Parameters: Haematology
Haematocrit abnormality: <=32%
|
2 participants
|
2 participants
|
0 participants
|
—
|
|
Frequency of Patients With Possibly Clinically Significant Abnormal Laboratory Parameters: Haematology
Haemoglobin abnormality:Female ≤9.5;Male ≤11.5g/dL
|
7 participants
|
4 participants
|
2 participants
|
—
|
|
Frequency of Patients With Possibly Clinically Significant Abnormal Laboratory Parameters: Haematology
Red Blood Cells abnormality: < 3* 10^12/L
|
0 participants
|
0 participants
|
0 participants
|
—
|
|
Frequency of Patients With Possibly Clinically Significant Abnormal Laboratory Parameters: Haematology
White Blood Cells abnormal decrease: < 3 * 10^9/L
|
0 participants
|
3 participants
|
1 participants
|
—
|
|
Frequency of Patients With Possibly Clinically Significant Abnormal Laboratory Parameters: Haematology
White Blood Cells abnormal increase: <20.1*10^9/L
|
0 participants
|
1 participants
|
0 participants
|
—
|
|
Frequency of Patients With Possibly Clinically Significant Abnormal Laboratory Parameters: Haematology
Platelets abnormal decrease: <= 75* 10^9/L
|
0 participants
|
0 participants
|
1 participants
|
—
|
|
Frequency of Patients With Possibly Clinically Significant Abnormal Laboratory Parameters: Haematology
Platelets abnormal increase: >= 700* 10^9/L
|
0 participants
|
0 participants
|
0 participants
|
—
|
PRIMARY outcome
Timeframe: 54 weeksPopulation: TS and observed cases (OC). In treatment group L2.5+M500, the number of patients analysed was 224 for lactate dehydrogenase abnormality and total bilirubin abnormality due to anailable data.
ULN means upper limit of normal
Outcome measures
| Measure |
M1000
n=168 Participants
Metformin 1000mg monotherapy twice daily
|
L2.5+M500
n=225 Participants
Linagliptin 2.5mg and metformin 500mg twice daily
|
L2.5+M1000
n=171 Participants
Linagliptin 2.5mg and metformin 1000mg twice daily
|
Post-treat
7 days follow-up period
|
|---|---|---|---|---|
|
Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry
Calcium abnormal increase: > 3 mmol/L
|
0 participants
|
1 participants
|
0 participants
|
—
|
|
Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry
Eosinophils abnormality : ≥ 10%
|
2 participants
|
4 participants
|
6 participants
|
—
|
|
Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry
Sodium abnormal decrease: < 130 mmol/L
|
0 participants
|
1 participants
|
2 participants
|
—
|
|
Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry
Sodium abnormal increase: > 160 mmol/L
|
1 participants
|
0 participants
|
0 participants
|
—
|
|
Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry
Potassium abnormal decrease: < 3 mmol/L
|
0 participants
|
0 participants
|
0 participants
|
—
|
|
Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry
Potassium abnormal increase: > 5.8 mmol/L
|
2 participants
|
2 participants
|
4 participants
|
—
|
|
Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry
Calcium abnormal decrease: < 1.8 mmol/L
|
2 participants
|
1 participants
|
0 participants
|
—
|
|
Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry
Phosphate abnormal decrease: < 0.7 mmol/L
|
1 participants
|
0 participants
|
0 participants
|
—
|
|
Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry
Phosphate abnormal increase: > 1.7 mmol/L
|
0 participants
|
2 participants
|
1 participants
|
—
|
|
Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry
Aspartate Transaminase abnormality: ≥3xULN
|
3 participants
|
2 participants
|
2 participants
|
—
|
|
Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry
Alanine Transaminase (ALT) abnormality: >= 3 x ULN
|
4 participants
|
3 participants
|
2 participants
|
—
|
|
Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry
Alkaline phosphatase abnormality: >= 2 x ULN
|
1 participants
|
0 participants
|
0 participants
|
—
|
|
Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry
γ-glutamyl transpeptidase (GGT) increase:≥3ULN
|
8 participants
|
5 participants
|
7 participants
|
—
|
|
Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry
Lactate dehydrogenase abnormality: >= 3 x ULN
|
0 participants
|
0 participants
|
0 participants
|
—
|
|
Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry
Creatine kinase abnormality: >= 3 x ULN
|
3 participants
|
1 participants
|
2 participants
|
—
|
|
Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry
Amylase: > 1.5 x ULN
|
2 participants
|
5 participants
|
4 participants
|
—
|
|
Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry
Total cholesterol abnormality: > 300 mg/dL
|
0 participants
|
0 participants
|
1 participants
|
—
|
|
Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry
Creatinine abnormality: >= 1.5 mg/dL
|
0 participants
|
1 participants
|
0 participants
|
—
|
|
Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry
Total bilirubin abnormality: >= 2 mg/dL
|
0 participants
|
1 participants
|
0 participants
|
—
|
|
Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry
Triglyceride abnormality: >300 mg/dL
|
14 participants
|
14 participants
|
10 participants
|
—
|
|
Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry
Uric acid abnormality:Female: >10;Male: >11 mg/dL
|
4 participants
|
3 participants
|
6 participants
|
—
|
|
Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry
Albumin abnormality: <2.5 g/dL
|
0 participants
|
1 participants
|
0 participants
|
—
|
|
Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry
Bicarbonate abnormal decrease: <21 mmol/L
|
0 participants
|
0 participants
|
2 participants
|
—
|
PRIMARY outcome
Timeframe: Baseline and drug stop (up to 54 weeks) + 7 daysPopulation: Treated Set (TS)
Frequency of patients with adverse events by treatment, primary system organ class and preferred term
Outcome measures
| Measure |
M1000
n=170 Participants
Metformin 1000mg monotherapy twice daily
|
L2.5+M500
n=225 Participants
Linagliptin 2.5mg and metformin 500mg twice daily
|
L2.5+M1000
n=171 Participants
Linagliptin 2.5mg and metformin 1000mg twice daily
|
Post-treat
n=566 Participants
7 days follow-up period
|
|---|---|---|---|---|
|
Clinical Relevant Drug-related Abnormal Findings in Physical Examination and ECG as Reported as AE
Cardiogenic shock
|
0 participants
|
0 participants
|
1 participants
|
0 participants
|
|
Clinical Relevant Drug-related Abnormal Findings in Physical Examination and ECG as Reported as AE
Supraventricular tachycardia
|
0 participants
|
0 participants
|
1 participants
|
0 participants
|
SECONDARY outcome
Timeframe: 54 weeksPopulation: TS (OC) with non-missing data at visit
HbA1c is measured as a percentage. Thus, this change from baseline reflects the visit HbA1c percent minus the baseline HbA1c percent. Baseline is defined as visit 1 of 1218.52.
Outcome measures
| Measure |
M1000
n=168 Participants
Metformin 1000mg monotherapy twice daily
|
L2.5+M500
n=225 Participants
Linagliptin 2.5mg and metformin 500mg twice daily
|
L2.5+M1000
n=171 Participants
Linagliptin 2.5mg and metformin 1000mg twice daily
|
Post-treat
7 days follow-up period
|
|---|---|---|---|---|
|
Change in HbA1c From Baseline Over Time
Change in HbA1c to week 6 (n=157, 207 and 166)
|
-0.06 Percentage
Standard Deviation 0.41
|
-0.24 Percentage
Standard Deviation 0.51
|
-0.26 Percentage
Standard Deviation 0.59
|
—
|
|
Change in HbA1c From Baseline Over Time
Change in HbA1c to week 18 (n=136, 184 and 147)
|
-0.08 Percentage
Standard Deviation 0.56
|
-0.29 Percentage
Standard Deviation 0.79
|
-0.34 Percentage
Standard Deviation 0.93
|
—
|
|
Change in HbA1c From Baseline Over Time
Change in HbA1c to week 30 (n=121, 165 and 134)
|
-0.10 Percentage
Standard Deviation 0.82
|
-0.41 Percentage
Standard Deviation 0.80
|
-0.36 Percentage
Standard Deviation 0.87
|
—
|
|
Change in HbA1c From Baseline Over Time
Change in HbA1c to week 42 (n=110, 152 and 127)
|
-0.14 Percentage
Standard Deviation 0.78
|
-0.35 Percentage
Standard Deviation 0.80
|
-0.28 Percentage
Standard Deviation 1.00
|
—
|
|
Change in HbA1c From Baseline Over Time
Change in HbA1c to week 54 (n=98, 132 and 117)
|
-0.06 Percentage
Standard Deviation 0.77
|
-0.28 Percentage
Standard Deviation 0.86
|
-0.24 Percentage
Standard Deviation 0.91
|
—
|
SECONDARY outcome
Timeframe: 54 weeksPopulation: Treated Set with non completers considered as failures (NCF)
Outcome measures
| Measure |
M1000
n=170 Participants
Metformin 1000mg monotherapy twice daily
|
L2.5+M500
n=225 Participants
Linagliptin 2.5mg and metformin 500mg twice daily
|
L2.5+M1000
n=171 Participants
Linagliptin 2.5mg and metformin 1000mg twice daily
|
Post-treat
7 days follow-up period
|
|---|---|---|---|---|
|
Number of Patients With HbA1c <7.0% After 54 Weeks
No
|
119 participant
|
168 participant
|
104 participant
|
—
|
|
Number of Patients With HbA1c <7.0% After 54 Weeks
Yes
|
51 participant
|
57 participant
|
67 participant
|
—
|
SECONDARY outcome
Timeframe: 54 weeksPopulation: Treated Set with non completers considered as failures (NCF)
Outcome measures
| Measure |
M1000
n=170 Participants
Metformin 1000mg monotherapy twice daily
|
L2.5+M500
n=225 Participants
Linagliptin 2.5mg and metformin 500mg twice daily
|
L2.5+M1000
n=171 Participants
Linagliptin 2.5mg and metformin 1000mg twice daily
|
Post-treat
7 days follow-up period
|
|---|---|---|---|---|
|
Number of Patients With HbA1c <6.5% Over Time
No
|
148 participant
|
196 participant
|
130 participant
|
—
|
|
Number of Patients With HbA1c <6.5% Over Time
Yes
|
22 participant
|
29 participant
|
41 participant
|
—
|
SECONDARY outcome
Timeframe: 54 weeksPopulation: Treated Set with non completers considered as failures (NCF)
Outcome measures
| Measure |
M1000
n=170 Participants
Metformin 1000mg monotherapy twice daily
|
L2.5+M500
n=225 Participants
Linagliptin 2.5mg and metformin 500mg twice daily
|
L2.5+M1000
n=171 Participants
Linagliptin 2.5mg and metformin 1000mg twice daily
|
Post-treat
7 days follow-up period
|
|---|---|---|---|---|
|
Number of Patients With HbA1c of at Least <0.5% Over Time
No
|
143 participant
|
176 participant
|
135 participant
|
—
|
|
Number of Patients With HbA1c of at Least <0.5% Over Time
Yes
|
27 participant
|
49 participant
|
36 participant
|
—
|
SECONDARY outcome
Timeframe: 54 weeksPopulation: TS (OC) with non-missing data at visit
Baseline is defined as visit 1 of 1218.52.
Outcome measures
| Measure |
M1000
n=168 Participants
Metformin 1000mg monotherapy twice daily
|
L2.5+M500
n=225 Participants
Linagliptin 2.5mg and metformin 500mg twice daily
|
L2.5+M1000
n=171 Participants
Linagliptin 2.5mg and metformin 1000mg twice daily
|
Post-treat
7 days follow-up period
|
|---|---|---|---|---|
|
Change in FPG From Baseline Over Time
Change in FPG to week 2 (n=158, 200 and 158)
|
-4.36 mg/dL
Standard Deviation 27.86
|
-12.22 mg/dL
Standard Deviation 28.70
|
-10.57 mg/dL
Standard Deviation 28.15
|
—
|
|
Change in FPG From Baseline Over Time
Change in FPG to week 6 (n=152, 189 and 157)
|
-4.18 mg/dL
Standard Deviation 32.68
|
-13.28 mg/dL
Standard Deviation 27.36
|
-13.46 mg/dL
Standard Deviation 32.97
|
—
|
|
Change in FPG From Baseline Over Time
Change in FPG to week 18 (n=133, 174 and 142)
|
-1.14 mg/dL
Standard Deviation 43.18
|
-11.76 mg/dL
Standard Deviation 33.10
|
-12.88 mg/dL
Standard Deviation 33.74
|
—
|
|
Change in FPG From Baseline Over Time
Change in FPG to week 30 (n=116, 156 and 130)
|
-7.22 mg/dL
Standard Deviation 41.67
|
-13.49 mg/dL
Standard Deviation 33.68
|
-13.90 mg/dL
Standard Deviation 32.07
|
—
|
|
Change in FPG From Baseline Over Time
Change in FPG to week 42 (n=103, 149 and 124)
|
-7.43 mg/dL
Standard Deviation 30.48
|
-9.46 mg/dL
Standard Deviation 33.61
|
-13.10 mg/dL
Standard Deviation 34.96
|
—
|
|
Change in FPG From Baseline Over Time
Change in FPG to week 54 (n=93, 132 and 115)
|
-6.02 mg/dL
Standard Deviation 29.25
|
-7.24 mg/dL
Standard Deviation 36.27
|
-9.82 mg/dL
Standard Deviation 31.83
|
—
|
SECONDARY outcome
Timeframe: 54 weeksPopulation: TS
Outcome measures
| Measure |
M1000
n=170 Participants
Metformin 1000mg monotherapy twice daily
|
L2.5+M500
n=225 Participants
Linagliptin 2.5mg and metformin 500mg twice daily
|
L2.5+M1000
n=171 Participants
Linagliptin 2.5mg and metformin 1000mg twice daily
|
Post-treat
7 days follow-up period
|
|---|---|---|---|---|
|
Number of Patients With Rescue Therapy
No
|
128 Number of patients
|
163 Number of patients
|
147 Number of patients
|
—
|
|
Number of Patients With Rescue Therapy
Yes
|
42 Number of patients
|
62 Number of patients
|
24 Number of patients
|
—
|
SECONDARY outcome
Timeframe: 78 weeksPopulation: Non-switcher set (OC) with non-missing data at visit. Only patients who continued on the same treatment in both studies are included
HbA1c is measured as a percentage. Thus, this change from baseline reflects the visit HbA1c percent minus the baseline HbA1c percent. Baseline is defined as visit 3 from study 1218.46 (NCT00915772).
Outcome measures
| Measure |
M1000
n=109 Participants
Metformin 1000mg monotherapy twice daily
|
L2.5+M500
n=113 Participants
Linagliptin 2.5mg and metformin 500mg twice daily
|
L2.5+M1000
n=111 Participants
Linagliptin 2.5mg and metformin 1000mg twice daily
|
Post-treat
7 days follow-up period
|
|---|---|---|---|---|
|
Change in HbA1c From Baseline Over Time
Change in HbA1c to week 30 (n=102, 103 and 108)
|
-1.19 Percentage
Standard Deviation 0.98
|
-1.34 Percentage
Standard Deviation 0.91
|
-1.74 Percentage
Standard Deviation 0.98
|
—
|
|
Change in HbA1c From Baseline Over Time
Change in HbA1c to week 42 (n=90, 92 and 95)
|
-1.16 Percentage
Standard Deviation 0.98
|
-1.31 Percentage
Standard Deviation 0.99
|
-1.62 Percentage
Standard Deviation 1.05
|
—
|
|
Change in HbA1c From Baseline Over Time
Change in HbA1c to week 54 (n=81, 81 and 87)
|
-1.20 Percentage
Standard Deviation 1.14
|
-1.41 Percentage
Standard Deviation 1.03
|
-1.73 Percentage
Standard Deviation 0.99
|
—
|
|
Change in HbA1c From Baseline Over Time
Change in HbA1c to week 66 (n=74, 73 and 84)
|
-1.26 Percentage
Standard Deviation 1.02
|
-1.42 Percentage
Standard Deviation 0.93
|
-1.65 Percentage
Standard Deviation 1.09
|
—
|
|
Change in HbA1c From Baseline Over Time
Change in HbA1c to week 78 (n=66, 66 and 78)
|
-1.25 Percentage
Standard Deviation 0.91
|
-1.32 Percentage
Standard Deviation 1.06
|
-1.63 Percentage
Standard Deviation 1.05
|
—
|
Adverse Events
M1000
Serious events: 7 serious events
Other events: 63 other events
Deaths: 0 deaths
L2.5+M500
Serious events: 12 serious events
Other events: 87 other events
Deaths: 0 deaths
L2.5+M1000
Serious events: 14 serious events
Other events: 77 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
M1000
n=170 participants at risk
Metformin 1000 mg twice daily
|
L2.5+M500
n=225 participants at risk
Linagliptin 2.5 mg + Metformin 500 mg twice daily
|
L2.5+M1000
n=171 participants at risk
Linagliptin 2.5 mg + Metformin 1000 mg twice daily
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/170 • 54 weeks
|
0.44%
1/225 • 54 weeks
|
0.00%
0/171 • 54 weeks
|
|
Cardiac disorders
Acute coronary syndrome
|
0.00%
0/170 • 54 weeks
|
0.44%
1/225 • 54 weeks
|
0.00%
0/171 • 54 weeks
|
|
Cardiac disorders
Acute myocardial infarction
|
0.59%
1/170 • 54 weeks
|
0.89%
2/225 • 54 weeks
|
0.00%
0/171 • 54 weeks
|
|
Cardiac disorders
Angina pectoris
|
0.00%
0/170 • 54 weeks
|
0.00%
0/225 • 54 weeks
|
0.58%
1/171 • 54 weeks
|
|
Cardiac disorders
Atrial fibrillation
|
0.59%
1/170 • 54 weeks
|
0.00%
0/225 • 54 weeks
|
0.00%
0/171 • 54 weeks
|
|
Cardiac disorders
Atrial flutter
|
0.00%
0/170 • 54 weeks
|
0.00%
0/225 • 54 weeks
|
0.58%
1/171 • 54 weeks
|
|
Cardiac disorders
Cardiac disorder
|
0.00%
0/170 • 54 weeks
|
0.44%
1/225 • 54 weeks
|
0.00%
0/171 • 54 weeks
|
|
Cardiac disorders
Cardiogenic shock
|
0.00%
0/170 • 54 weeks
|
0.00%
0/225 • 54 weeks
|
0.58%
1/171 • 54 weeks
|
|
Cardiac disorders
Coronary artery disease
|
0.00%
0/170 • 54 weeks
|
0.00%
0/225 • 54 weeks
|
0.58%
1/171 • 54 weeks
|
|
Cardiac disorders
Myocardial ischaemia
|
0.00%
0/170 • 54 weeks
|
0.44%
1/225 • 54 weeks
|
0.00%
0/171 • 54 weeks
|
|
Cardiac disorders
Supraventricular tachycardia
|
0.00%
0/170 • 54 weeks
|
0.00%
0/225 • 54 weeks
|
0.58%
1/171 • 54 weeks
|
|
Congenital, familial and genetic disorders
Holoprosencephaly
|
0.00%
0/170 • 54 weeks
|
0.00%
0/225 • 54 weeks
|
0.58%
1/171 • 54 weeks
|
|
Eye disorders
Cataract
|
0.00%
0/170 • 54 weeks
|
0.44%
1/225 • 54 weeks
|
0.00%
0/171 • 54 weeks
|
|
Gastrointestinal disorders
Haemorrhoids
|
0.59%
1/170 • 54 weeks
|
0.00%
0/225 • 54 weeks
|
0.58%
1/171 • 54 weeks
|
|
Hepatobiliary disorders
Cholecystitis chronic
|
0.00%
0/170 • 54 weeks
|
0.00%
0/225 • 54 weeks
|
0.58%
1/171 • 54 weeks
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.00%
0/170 • 54 weeks
|
0.00%
0/225 • 54 weeks
|
0.58%
1/171 • 54 weeks
|
|
Infections and infestations
Dacryocystitis
|
0.59%
1/170 • 54 weeks
|
0.00%
0/225 • 54 weeks
|
0.00%
0/171 • 54 weeks
|
|
Infections and infestations
Febrile infection
|
0.59%
1/170 • 54 weeks
|
0.00%
0/225 • 54 weeks
|
0.00%
0/171 • 54 weeks
|
|
Infections and infestations
Herpes zoster
|
0.00%
0/170 • 54 weeks
|
0.44%
1/225 • 54 weeks
|
0.00%
0/171 • 54 weeks
|
|
Infections and infestations
Pneumonia
|
0.59%
1/170 • 54 weeks
|
0.00%
0/225 • 54 weeks
|
0.58%
1/171 • 54 weeks
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/170 • 54 weeks
|
0.00%
0/225 • 54 weeks
|
0.58%
1/171 • 54 weeks
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/170 • 54 weeks
|
0.44%
1/225 • 54 weeks
|
0.58%
1/171 • 54 weeks
|
|
Injury, poisoning and procedural complications
Head injury
|
0.00%
0/170 • 54 weeks
|
0.44%
1/225 • 54 weeks
|
0.00%
0/171 • 54 weeks
|
|
Injury, poisoning and procedural complications
Hip fracture
|
0.59%
1/170 • 54 weeks
|
0.00%
0/225 • 54 weeks
|
0.00%
0/171 • 54 weeks
|
|
Injury, poisoning and procedural complications
Joint dislocation
|
0.00%
0/170 • 54 weeks
|
0.44%
1/225 • 54 weeks
|
0.00%
0/171 • 54 weeks
|
|
Injury, poisoning and procedural complications
Limb injury
|
0.00%
0/170 • 54 weeks
|
0.00%
0/225 • 54 weeks
|
0.58%
1/171 • 54 weeks
|
|
Injury, poisoning and procedural complications
Rib fracture
|
0.00%
0/170 • 54 weeks
|
0.44%
1/225 • 54 weeks
|
0.00%
0/171 • 54 weeks
|
|
Injury, poisoning and procedural complications
Road traffic accident
|
0.00%
0/170 • 54 weeks
|
0.44%
1/225 • 54 weeks
|
1.2%
2/171 • 54 weeks
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.59%
1/170 • 54 weeks
|
0.00%
0/225 • 54 weeks
|
0.00%
0/171 • 54 weeks
|
|
Musculoskeletal and connective tissue disorders
Rotator cuff syndrome
|
0.00%
0/170 • 54 weeks
|
0.00%
0/225 • 54 weeks
|
0.58%
1/171 • 54 weeks
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer
|
0.00%
0/170 • 54 weeks
|
0.44%
1/225 • 54 weeks
|
0.00%
0/171 • 54 weeks
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Renal cancer metastatic
|
0.00%
0/170 • 54 weeks
|
0.44%
1/225 • 54 weeks
|
0.00%
0/171 • 54 weeks
|
|
Nervous system disorders
Cerebrovascular accident
|
0.59%
1/170 • 54 weeks
|
0.00%
0/225 • 54 weeks
|
0.00%
0/171 • 54 weeks
|
|
Nervous system disorders
Convulsion
|
0.00%
0/170 • 54 weeks
|
0.44%
1/225 • 54 weeks
|
0.00%
0/171 • 54 weeks
|
|
Nervous system disorders
Ischaemic stroke
|
0.00%
0/170 • 54 weeks
|
0.44%
1/225 • 54 weeks
|
0.00%
0/171 • 54 weeks
|
|
Renal and urinary disorders
Calculus bladder
|
0.00%
0/170 • 54 weeks
|
0.00%
0/225 • 54 weeks
|
0.58%
1/171 • 54 weeks
|
|
Reproductive system and breast disorders
Benign prostatic hyperplasia
|
0.00%
0/170 • 54 weeks
|
0.00%
0/225 • 54 weeks
|
0.58%
1/171 • 54 weeks
|
Other adverse events
| Measure |
M1000
n=170 participants at risk
Metformin 1000 mg twice daily
|
L2.5+M500
n=225 participants at risk
Linagliptin 2.5 mg + Metformin 500 mg twice daily
|
L2.5+M1000
n=171 participants at risk
Linagliptin 2.5 mg + Metformin 1000 mg twice daily
|
|---|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
2.4%
4/170 • 54 weeks
|
3.6%
8/225 • 54 weeks
|
7.0%
12/171 • 54 weeks
|
|
Infections and infestations
Nasopharyngitis
|
5.3%
9/170 • 54 weeks
|
4.0%
9/225 • 54 weeks
|
7.0%
12/171 • 54 weeks
|
|
Infections and infestations
Urinary tract infection
|
2.4%
4/170 • 54 weeks
|
4.0%
9/225 • 54 weeks
|
5.3%
9/171 • 54 weeks
|
|
Investigations
Glomerular filtration rate decreased
|
3.5%
6/170 • 54 weeks
|
6.2%
14/225 • 54 weeks
|
6.4%
11/171 • 54 weeks
|
|
Investigations
Glycosylated haemoglobin increased
|
5.3%
9/170 • 54 weeks
|
5.3%
12/225 • 54 weeks
|
2.3%
4/171 • 54 weeks
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
8.2%
14/170 • 54 weeks
|
8.0%
18/225 • 54 weeks
|
9.9%
17/171 • 54 weeks
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
11.8%
20/170 • 54 weeks
|
12.9%
29/225 • 54 weeks
|
6.4%
11/171 • 54 weeks
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
2.4%
4/170 • 54 weeks
|
4.9%
11/225 • 54 weeks
|
6.4%
11/171 • 54 weeks
|
|
Vascular disorders
Hypertension
|
5.3%
9/170 • 54 weeks
|
3.6%
8/225 • 54 weeks
|
5.8%
10/171 • 54 weeks
|
Additional Information
Boehringer Ingelheim Call Center
Boehringer Ingelheim Pharmaceuticals
Phone: 1-800-243-0127
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee Other - Any publication of the result of this trial must be consistent with the Boehringer Ingelheim publication policy. The rights of the investigator and of the sponsor with regard to publication of the results of this trial are described in the investigator contract.
- Publication restrictions are in place
Restriction type: OTHER