Trial Outcomes & Findings for Linagliptin 2.5 mg Twice Daily Versus 5 mg Once Daily as add-on Therapy to Twice Daily Metformin in Type 2 Diabetes (NCT NCT01012037)

NCT ID: NCT01012037

Last Updated: 2014-06-27

Results Overview

HbA1c is measured as a percentage. Thus, this change from baseline reflects the Week 12 HbA1c percent minus the baseline HbA1c percent. Treatment means are adjusted for baseline HbA1c and use of prior oral antidiabetics (OADs) in addition to background metformin.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

491 participants

Primary outcome timeframe

Baseline and week 12

Results posted on

2014-06-27

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo Patients treated with matching placebo	Lina 2.5 Twice Daily (Bid) Patients treated with Linagliptin 2.5mg bid	Lina 5 Once Daily (qd) Patients treated with Linagliptin 5mg qd
Overall Study STARTED	44	223	224
Overall Study COMPLETED	43	207	214
Overall Study NOT COMPLETED	1	16	10

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Patients treated with matching placebo	Lina 2.5 Twice Daily (Bid) Patients treated with Linagliptin 2.5mg bid	Lina 5 Once Daily (qd) Patients treated with Linagliptin 5mg qd
Overall Study Adverse Event	0	8	3
Overall Study Protocol Violation	0	3	5
Overall Study Withdrawal by Subject	0	4	1
Overall Study Other reason (not specified)	1	1	1

Baseline Characteristics

Linagliptin 2.5 mg Twice Daily Versus 5 mg Once Daily as add-on Therapy to Twice Daily Metformin in Type 2 Diabetes

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=44 Participants Patients treated with matching placebo	Lina 2.5 Twice Daily (Bid) n=223 Participants Patients treated with Linagliptin 2.5mg bid	Lina 5 Once Daily (qd) n=224 Participants Patients treated with Linagliptin 5mg qd	Total n=491 Participants Total of all reporting groups
Age, Continuous	59.9 Years STANDARD_DEVIATION 10.7 • n=5 Participants	58.7 Years STANDARD_DEVIATION 9.9 • n=7 Participants	58.4 Years STANDARD_DEVIATION 10.6 • n=5 Participants	58.6 Years STANDARD_DEVIATION 10.3 • n=4 Participants
Sex: Female, Male Female	23 Participants n=5 Participants	85 Participants n=7 Participants	103 Participants n=5 Participants	211 Participants n=4 Participants
Sex: Female, Male Male	21 Participants n=5 Participants	138 Participants n=7 Participants	121 Participants n=5 Participants	280 Participants n=4 Participants
Body Mass Index (BMI) continuous	28.65 kg/m^2 STANDARD_DEVIATION 5.53 • n=5 Participants	29.77 kg/m^2 STANDARD_DEVIATION 5.23 • n=7 Participants	29.55 kg/m^2 STANDARD_DEVIATION 4.95 • n=5 Participants	29.57 kg/m^2 STANDARD_DEVIATION 5.13 • n=4 Participants
Glycosylated hemoglobin (HbA1c)	7.92 percent STANDARD_DEVIATION 0.74 • n=5 Participants	7.96 percent STANDARD_DEVIATION 0.78 • n=7 Participants	7.98 percent STANDARD_DEVIATION 0.72 • n=5 Participants	7.97 percent STANDARD_DEVIATION 0.75 • n=4 Participants
Fasting blood plasma glucose (FPG)	166.2 mg/dL STANDARD_DEVIATION 40.3 • n=5 Participants	164.1 mg/dL STANDARD_DEVIATION 41.8 • n=7 Participants	165.8 mg/dL STANDARD_DEVIATION 35.1 • n=5 Participants	165.1 mg/dL STANDARD_DEVIATION 38.6 • n=4 Participants

PRIMARY outcome

Timeframe: Baseline and week 12

Population: The Full Analysis Set (FAS) included all treated patients with a baseline and at least one on-treatment HbA1c measurement available. Last observation carried forward (LOCF) was used as the imputation rule.

Outcome measures

Outcome measures
Measure	Placebo n=43 Participants Patients treated with matching placebo	Lina 2.5 Twice Daily (Bid) n=214 Participants Patients treated with Linagliptin 2.5mg bid	Lina 5 Once Daily (qd) n=221 Participants Patients treated with Linagliptin 5mg qd
HbA1c Change From Baseline at Week 12	0.28 percent Standard Error 0.11	-0.46 percent Standard Error 0.05	-0.52 percent Standard Error 0.05

SECONDARY outcome

Timeframe: Baseline and week 6

Population: The Full Analysis Set (FAS) included all treated patients with a baseline and at least one on-treatment HbA1c measurement available. No imputation was performed. Patients without a Week 6 value were handled by the statistical model.

Mixed model includes treatment, baseline HbA1c, use of prior oral antidiabetics (OADs) in addition to background metformin, week repeated within patient, week by treatment interaction.

Outcome measures

Outcome measures
Measure	Placebo n=43 Participants Patients treated with matching placebo	Lina 2.5 Twice Daily (Bid) n=214 Participants Patients treated with Linagliptin 2.5mg bid	Lina 5 Once Daily (qd) n=221 Participants Patients treated with Linagliptin 5mg qd
HbA1c Change From Baseline at Week 6 From Mixed Model Repeated Measures (MMRM) Analysis	0.32 percent Standard Error 0.08	-0.34 percent Standard Error 0.04	-0.34 percent Standard Error 0.04

SECONDARY outcome

Timeframe: Baseline and week 12

Mixed model includes treatment, baseline HbA1c, use of prior oral antidiabetics (OADs) in addition to background metformin, week repeated within patient, week by treatment interaction.

Outcome measures

Outcome measures
Measure	Placebo n=43 Participants Patients treated with matching placebo	Lina 2.5 Twice Daily (Bid) n=214 Participants Patients treated with Linagliptin 2.5mg bid	Lina 5 Once Daily (qd) n=221 Participants Patients treated with Linagliptin 5mg qd
HbA1c Change From Baseline at Week 12 From Mixed Model Repeated Measures (MMRM) Analysis	0.27 percent Standard Error 0.11	-0.51 percent Standard Error 0.05	-0.55 percent Standard Error 0.05

SECONDARY outcome

Timeframe: Baseline and week 12

Population: Patients from FAS with values for FPG at baseline and on-treatment. Last observation carried forward (LOCF) was used as the imputation rule.

Change from baseline reflects the Week 12 FPG minus the baseline FPG. Treatment means are adjusted for baseline HbA1c, baseline fasting plasma glucose and use of prior oral antidiabetics (OADs) in addition to background metformin.

Outcome measures

Outcome measures
Measure	Placebo n=40 Participants Patients treated with matching placebo	Lina 2.5 Twice Daily (Bid) n=203 Participants Patients treated with Linagliptin 2.5mg bid	Lina 5 Once Daily (qd) n=213 Participants Patients treated with Linagliptin 5mg qd
FPG Change From Baseline at Week 12	-3.5 mg/dL Standard Error 4.2	-17.2 mg/dL Standard Error 1.9	-21.3 mg/dL Standard Error 1.9

SECONDARY outcome

Timeframe: Baseline and week 6

Population: Patients from FAS with values for FPG at baseline and on-treatment. No imputation was performed. Patients without a Week 12 value were handled by the statistical model.

Mixed model includes treatment, baseline HbA1c, baseline FPG, use of prior oral antidiabetics (OADs) in addition to background metformin, week repeated within patient, week by treatment interaction.

Outcome measures

Outcome measures
Measure	Placebo n=40 Participants Patients treated with matching placebo	Lina 2.5 Twice Daily (Bid) n=203 Participants Patients treated with Linagliptin 2.5mg bid	Lina 5 Once Daily (qd) n=213 Participants Patients treated with Linagliptin 5mg qd
FPG Change From Baseline at Week 6 From Mixed Model Repeated Measures (MMRM) Analysis	-1.2 percent Standard Error 4.1	-17.8 percent Standard Error 1.9	-20.1 percent Standard Error 1.8

SECONDARY outcome

Timeframe: Baseline and week 12

Population: Patients from FAS with values for FPG at baseline and on-treatment. No imputation was performed. Patients without a Week 12 value were handled by the statistical model.

Mixed model includes treatment, baseline HbA1c, baseline FPG, use of prior oral antidiabetics (OADs) in addition to background metformin, week repeated within patient, week by treatment interaction.

Outcome measures

Outcome measures
Measure	Placebo n=40 Participants Patients treated with matching placebo	Lina 2.5 Twice Daily (Bid) n=203 Participants Patients treated with Linagliptin 2.5mg bid	Lina 5 Once Daily (qd) n=213 Participants Patients treated with Linagliptin 5mg qd
FPG Change From Baseline at Week 12 From Mixed Model Repeated Measures (MMRM) Analysis	-8.7 percent Standard Error 5.0	-18.7 percent Standard Error 2.3	-23.9 percent Standard Error 2.2

SECONDARY outcome

Timeframe: Week 12

Population: The Full Analysis Set (FAS) included all treated patients with a baseline and at least one on-treatment HbA1c measurement available. Patients without a value at Week 12 were analysed as non-responders

Percentage of patients with HbA1c lowering by at least 0.5% after 12 weeks. The analysis was performed on the full analysis set (FAS) using NCF.

Outcome measures

Outcome measures
Measure	Placebo n=43 Participants Patients treated with matching placebo	Lina 2.5 Twice Daily (Bid) n=214 Participants Patients treated with Linagliptin 2.5mg bid	Lina 5 Once Daily (qd) n=221 Participants Patients treated with Linagliptin 5mg qd
Percentage of Patients With HbA1c Lowering by 0.5% or More at Week 12	16.3 percent	55.1 percent	59.7 percent

SECONDARY outcome

Timeframe: 12 weeks

Percentage of patients with rescue therapy at Week 12. The analysis was performed on the full analysis set (FAS) using OC.

Outcome measures

Outcome measures
Measure	Placebo n=43 Participants Patients treated with matching placebo	Lina 2.5 Twice Daily (Bid) n=214 Participants Patients treated with Linagliptin 2.5mg bid	Lina 5 Once Daily (qd) n=221 Participants Patients treated with Linagliptin 5mg qd
Percentage of Patients With Rescue Therapy	7.0 percent	3.7 percent	1.8 percent

SECONDARY outcome

Timeframe: 12 weeks

Population: FAS (NCF) with baseline HbA1c \>= 7.0%

Percentage of those patients with baseline HbA1c \>= 7.0% who had HbA1c \< 7% at Week 12. The analysis was performed on the full analysis set (FAS) using NCF.

Outcome measures

Outcome measures
Measure	Placebo n=40 Participants Patients treated with matching placebo	Lina 2.5 Twice Daily (Bid) n=206 Participants Patients treated with Linagliptin 2.5mg bid	Lina 5 Once Daily (qd) n=215 Participants Patients treated with Linagliptin 5mg qd
The Occurrence of a Treat to Target Efficacy Response (HbA1c <7.0%) After 12 Weeks of Treatment	10.0 percentage of participants	34.0 percentage of participants	33.0 percentage of participants

SECONDARY outcome

Timeframe: 12 weeks

Population: FAS (NCF) with baseline HbA1c \>= 6.5%

Percentage of those patients with baseline HbA1c \>= 6.5% who had HbA1c \< 6.5% at Week 12. The analysis was performed on the full analysis set (FAS) using NCF.

Outcome measures

Outcome measures
Measure	Placebo n=43 Participants Patients treated with matching placebo	Lina 2.5 Twice Daily (Bid) n=212 Participants Patients treated with Linagliptin 2.5mg bid	Lina 5 Once Daily (qd) n=221 Participants Patients treated with Linagliptin 5mg qd
The Occurrence of a Treat to Target Efficacy Response (HbA1c <6.5 %) After 12 Weeks of Treatment	0.0 percentage of participants	12.7 percentage of participants	11.8 percentage of participants

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Lina 2.5 Twice Daily (Bid)

Serious events: 9 serious events

Other events: 0 other events

Deaths: 0 deaths

Lina 5 Once Daily (qd)

Serious events: 5 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Adverse event data not reported

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 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

Measure	Placebo n=44 participants at risk Patients treated with matching placebo	Lina 2.5 Twice Daily (Bid) n=223 participants at risk Patients treated with Linagliptin 2.5mg bid	Lina 5 Once Daily (qd) n=224 participants at risk Patients treated with Linagliptin 5mg qd
Cardiac disorders Acute myocardial infarction	0.00% 0/44 • up to 12 weeks (drug stop) + 7 days (follow-up)	0.00% 0/223 • up to 12 weeks (drug stop) + 7 days (follow-up)	0.45% 1/224 • up to 12 weeks (drug stop) + 7 days (follow-up)
Cardiac disorders Angina pectoris	0.00% 0/44 • up to 12 weeks (drug stop) + 7 days (follow-up)	0.45% 1/223 • up to 12 weeks (drug stop) + 7 days (follow-up)	0.00% 0/224 • up to 12 weeks (drug stop) + 7 days (follow-up)
Gastrointestinal disorders Diarrhoea	0.00% 0/44 • up to 12 weeks (drug stop) + 7 days (follow-up)	0.00% 0/223 • up to 12 weeks (drug stop) + 7 days (follow-up)	0.45% 1/224 • up to 12 weeks (drug stop) + 7 days (follow-up)
Gastrointestinal disorders Rectal haemorrhage	0.00% 0/44 • up to 12 weeks (drug stop) + 7 days (follow-up)	0.45% 1/223 • up to 12 weeks (drug stop) + 7 days (follow-up)	0.00% 0/224 • up to 12 weeks (drug stop) + 7 days (follow-up)
Gastrointestinal disorders Vomiting	0.00% 0/44 • up to 12 weeks (drug stop) + 7 days (follow-up)	0.00% 0/223 • up to 12 weeks (drug stop) + 7 days (follow-up)	0.45% 1/224 • up to 12 weeks (drug stop) + 7 days (follow-up)
General disorders Chest pain	0.00% 0/44 • up to 12 weeks (drug stop) + 7 days (follow-up)	0.45% 1/223 • up to 12 weeks (drug stop) + 7 days (follow-up)	0.00% 0/224 • up to 12 weeks (drug stop) + 7 days (follow-up)
Infections and infestations Appendicitis	0.00% 0/44 • up to 12 weeks (drug stop) + 7 days (follow-up)	0.45% 1/223 • up to 12 weeks (drug stop) + 7 days (follow-up)	0.00% 0/224 • up to 12 weeks (drug stop) + 7 days (follow-up)
Infections and infestations Pneumonia	0.00% 0/44 • up to 12 weeks (drug stop) + 7 days (follow-up)	0.00% 0/223 • up to 12 weeks (drug stop) + 7 days (follow-up)	0.45% 1/224 • up to 12 weeks (drug stop) + 7 days (follow-up)
Injury, poisoning and procedural complications Ankle fracture	0.00% 0/44 • up to 12 weeks (drug stop) + 7 days (follow-up)	0.45% 1/223 • up to 12 weeks (drug stop) + 7 days (follow-up)	0.00% 0/224 • up to 12 weeks (drug stop) + 7 days (follow-up)
Injury, poisoning and procedural complications Fall	0.00% 0/44 • up to 12 weeks (drug stop) + 7 days (follow-up)	0.45% 1/223 • up to 12 weeks (drug stop) + 7 days (follow-up)	0.00% 0/224 • up to 12 weeks (drug stop) + 7 days (follow-up)
Injury, poisoning and procedural complications Fibula fracture	0.00% 0/44 • up to 12 weeks (drug stop) + 7 days (follow-up)	0.45% 1/223 • up to 12 weeks (drug stop) + 7 days (follow-up)	0.00% 0/224 • up to 12 weeks (drug stop) + 7 days (follow-up)
Injury, poisoning and procedural complications Muscle strain	0.00% 0/44 • up to 12 weeks (drug stop) + 7 days (follow-up)	0.00% 0/223 • up to 12 weeks (drug stop) + 7 days (follow-up)	0.45% 1/224 • up to 12 weeks (drug stop) + 7 days (follow-up)
Injury, poisoning and procedural complications Open fracture	0.00% 0/44 • up to 12 weeks (drug stop) + 7 days (follow-up)	0.45% 1/223 • up to 12 weeks (drug stop) + 7 days (follow-up)	0.00% 0/224 • up to 12 weeks (drug stop) + 7 days (follow-up)
Injury, poisoning and procedural complications Operative haemorrhage	0.00% 0/44 • up to 12 weeks (drug stop) + 7 days (follow-up)	0.45% 1/223 • up to 12 weeks (drug stop) + 7 days (follow-up)	0.00% 0/224 • up to 12 weeks (drug stop) + 7 days (follow-up)
Injury, poisoning and procedural complications Road traffic accident	0.00% 0/44 • up to 12 weeks (drug stop) + 7 days (follow-up)	0.00% 0/223 • up to 12 weeks (drug stop) + 7 days (follow-up)	0.45% 1/224 • up to 12 weeks (drug stop) + 7 days (follow-up)
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/44 • up to 12 weeks (drug stop) + 7 days (follow-up)	0.00% 0/223 • up to 12 weeks (drug stop) + 7 days (follow-up)	0.45% 1/224 • up to 12 weeks (drug stop) + 7 days (follow-up)
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.00% 0/44 • up to 12 weeks (drug stop) + 7 days (follow-up)	0.45% 1/223 • up to 12 weeks (drug stop) + 7 days (follow-up)	0.00% 0/224 • up to 12 weeks (drug stop) + 7 days (follow-up)
Nervous system disorders Syncope	0.00% 0/44 • up to 12 weeks (drug stop) + 7 days (follow-up)	0.45% 1/223 • up to 12 weeks (drug stop) + 7 days (follow-up)	0.00% 0/224 • up to 12 weeks (drug stop) + 7 days (follow-up)
Surgical and medical procedures Preoperative care	0.00% 0/44 • up to 12 weeks (drug stop) + 7 days (follow-up)	0.00% 0/223 • up to 12 weeks (drug stop) + 7 days (follow-up)	0.45% 1/224 • up to 12 weeks (drug stop) + 7 days (follow-up)