Trial Outcomes & Findings for Linagliptin and Metformin Versus Linagliptin in Newly Diagnosed, Untreated Type 2 Diabetes (NCT NCT01512979)

NCT ID: NCT01512979

Last Updated: 2014-05-20

Results Overview

HbA1c is measured as a percentage. The change from baseline is the Week 24 HbA1c minus the baseline HbA1c. Means are adjusted for treatment and continuous baseline HbA1c

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 316 participants
• Primary outcome timeframe: Baseline and 24 weeks
• Results posted on: 2014-05-20

Participant Flow

Participant milestones

Measure	Linagliptin 5mg + Metformin Patients treated with linagliptin 5mg and metformin IR (1500mg to 2000mg total daily dose)	Linagliptin 5mg Patients treated with linagliptin 5mg
Overall Study STARTED	159	157
Overall Study COMPLETED	140	135
Overall Study NOT COMPLETED	19	22

Reasons for withdrawal

Measure	Linagliptin 5mg + Metformin Patients treated with linagliptin 5mg and metformin IR (1500mg to 2000mg total daily dose)	Linagliptin 5mg Patients treated with linagliptin 5mg
Overall Study Adverse Event	2	2
Overall Study Protocol Violation	1	4
Overall Study Lost to Follow-up	2	5
Overall Study Withdrawal by Subject	1	2
Overall Study Reason other than stated above	13	9

Baseline Characteristics

Linagliptin and Metformin Versus Linagliptin in Newly Diagnosed, Untreated Type 2 Diabetes

Baseline characteristics by cohort

Measure	Linagliptin 5mg + Metformin n=159 Participants Patients treated with linagliptin 5mg and metformin IR (1500mg to 2000mg total daily dose)	Linagliptin 5mg n=157 Participants Patients treated with linagliptin 5mg	Total n=316 Participants Total of all reporting groups
Age, Continuous	49.0 years STANDARD_DEVIATION 10.9 • n=5 Participants	48.6 years STANDARD_DEVIATION 11.2 • n=7 Participants	48.8 years STANDARD_DEVIATION 11.0 • n=5 Participants
Sex: Female, Male Female	90 Participants n=5 Participants	80 Participants n=7 Participants	170 Participants n=5 Participants
Sex: Female, Male Male	69 Participants n=5 Participants	77 Participants n=7 Participants	146 Participants n=5 Participants
Baseline HbA1c	9.79 percentage STANDARD_DEVIATION 1.19 • n=5 Participants	9.88 percentage STANDARD_DEVIATION 1.10 • n=7 Participants	9.83 percentage STANDARD_DEVIATION 1.14 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline and 24 weeks

Population: Per Protocol completers cohort (PPCC): All patients randomised, treated with at least 1 dose of study drug, with a baseline HbA1c value without important protocol violations and who completed 24 weeks of treatment, were not treated with rescue medication and have an HbA1c measurement after 24 weeks of treatment.

HbA1c is measured as a percentage. The change from baseline is the Week 24 HbA1c minus the baseline HbA1c. Means are adjusted for treatment and continuous baseline HbA1c

Outcome measures

Measure	Linagliptin 5mg + Metformin n=132 Participants Patients treated with linagliptin 5mg and metformin IR (1500mg to 2000mg total daily dose)	Linagliptin 5mg n=113 Participants Patients treated with linagliptin 5mg
Change From Baseline in HbA1c After 24 Weeks	-2.81 percent Standard Error 0.12	-2.02 percent Standard Error 0.13

SECONDARY outcome

Timeframe: Baseline and 24 weeks

Population: Patients from PPCC (LOCF)

The change from baseline is the FPG after 24 weeks minus the baseline FPG. Means are adjusted for treatment, continuous baseline HbA1c and continuous baseline fasting plasma glucose.

Outcome measures

Measure	Linagliptin 5mg + Metformin n=132 Participants Patients treated with linagliptin 5mg and metformin IR (1500mg to 2000mg total daily dose)	Linagliptin 5mg n=113 Participants Patients treated with linagliptin 5mg
Change From Baseline in Fasting Plasma Glucose (FPG) After 24 Weeks of Treatment	-47.1 mg/dL Standard Error 3.8	-30.2 mg/dL Standard Error 4.2

SECONDARY outcome

Timeframe: Baseline, 6, 12, 18 and 24 weeks

Population: Patients from PPCC (observed cases)

HbA1c is measured as a percentage. The change from baseline is the HbA1c over time minus the baseline HbA1c. The model includes treatment, continuous baseline HbA1c in addition to week repeated within patient, week by baseline HbA1c interaction and week by treatment interaction.

Outcome measures

Measure	Linagliptin 5mg + Metformin n=132 Participants Patients treated with linagliptin 5mg and metformin IR (1500mg to 2000mg total daily dose)	Linagliptin 5mg n=113 Participants Patients treated with linagliptin 5mg
Change From Baseline in HbA1c by Visit Over Time Change to week 6	-1.97 percent Standard Error 0.09	-1.33 percent Standard Error 0.10
Change From Baseline in HbA1c by Visit Over Time Change to week 12	-2.69 percent Standard Error 0.11	-1.85 percent Standard Error 0.12
Change From Baseline in HbA1c by Visit Over Time Change to week 18	-2.79 percent Standard Error 0.11	-2.01 percent Standard Error 0.12
Change From Baseline in HbA1c by Visit Over Time Change to week 24	-2.81 percent Standard Error 0.12	-2.01 percent Standard Error 0.13

SECONDARY outcome

Timeframe: Baseline and 24 weeks

Population: Patients from PPCC. Non-completers considered as failures.

The proportion of patients who achieved HbA1c lowering by at least 0.5% after 24 weeks of treatment.The model includes treatment, and continuous baseline HbA1c.

Outcome measures

Measure	Linagliptin 5mg + Metformin n=132 Participants Patients treated with linagliptin 5mg and metformin IR (1500mg to 2000mg total daily dose)	Linagliptin 5mg n=113 Participants Patients treated with linagliptin 5mg
Occurrence of Relative Efficacy Response (HbA1c Lowering by at Least 0.5% After 24 Weeks of Treatment)	124 participants	92 participants

SECONDARY outcome

Timeframe: Baseline and 24 weeks

Population: Patients from PPCC. Non-completers considered as failures.

The proportion of patients who achieved HbA1c lowering by at least 1.0% after 24 weeks of treatment. The model includes treatment, and continuous baseline HbA1c.

Outcome measures

Measure	Linagliptin 5mg + Metformin n=132 Participants Patients treated with linagliptin 5mg and metformin IR (1500mg to 2000mg total daily dose)	Linagliptin 5mg n=113 Participants Patients treated with linagliptin 5mg
Occurrence of Relative Efficacy Response (HbA1c Lowering by at Least 1.0% After 24 Weeks of Treatment)	116 participants	82 participants

SECONDARY outcome

Timeframe: Baseline and 24 weeks

Population: Patients from PPCC. Non-completers considered as failures.

The proportion of patients who achieved HbA1c below 7.0% after 24 weeks of treatment. The model includes treatment, and continuous baseline HbA1c.

Outcome measures

Measure	Linagliptin 5mg + Metformin n=132 Participants Patients treated with linagliptin 5mg and metformin IR (1500mg to 2000mg total daily dose)	Linagliptin 5mg n=113 Participants Patients treated with linagliptin 5mg
Occurrence of Treat to Target Efficacy Response (HbA1c <7.0%) After 24 Weeks of Treatment	81 participants	45 participants

SECONDARY outcome

Timeframe: Baseline, 6, 12, 18 and 24 weeks

Population: Patients from PPCC, Observed Cases

The change from baseline is the FPG over time minus the baseline FPG. Means are adjusted for treatment, continuous baseline HbA1c, continuous baseline FPG in addition to week repeated within patient, week by baseline FPG interaction and week by treatment interaction.

Outcome measures

Measure	Linagliptin 5mg + Metformin n=132 Participants Patients treated with linagliptin 5mg and metformin IR (1500mg to 2000mg total daily dose)	Linagliptin 5mg n=113 Participants Patients treated with linagliptin 5mg
Change From Baseline in FPG by Visit Over Time Change to week 6	-52.3 mg/dL Standard Error 3.37	-31.9 mg/dL Standard Error 3.67
Change From Baseline in FPG by Visit Over Time Change to week 12	-54.1 mg/dL Standard Error 3.49	-30.5 mg/dL Standard Error 3.77
Change From Baseline in FPG by Visit Over Time Change to week 18	-52.4 mg/dL Standard Error 3.20	-35.4 mg/dL Standard Error 3.46
Change From Baseline in FPG by Visit Over Time Change to week 24	-47.1 mg/dL Standard Error 3.88	-30.1 mg/dL Standard Error 4.16

Adverse Events

Linagliptin 5mg + Metformin

Serious events: 3 serious events

Other events: 39 other events

Deaths: 0 deaths

Linagliptin 5mg

Serious events: 2 serious events

Other events: 51 other events

Deaths: 0 deaths

Serious adverse events

Measure	Linagliptin 5mg + Metformin n=159 participants at risk Patients treated with linagliptin 5mg and metformin IR (1500mg to 2000mg total daily dose)	Linagliptin 5mg n=157 participants at risk Patients treated with linagliptin 5mg
Cardiac disorders Coronary artery disease	0.00% 0/159 • Up to 28 weeks	0.64% 1/157 • Up to 28 weeks
Gastrointestinal disorders Small intestinal obstruction	0.63% 1/159 • Up to 28 weeks	0.00% 0/157 • Up to 28 weeks
Gastrointestinal disorders Umbilical hernia, obstructive	0.63% 1/159 • Up to 28 weeks	0.00% 0/157 • Up to 28 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Thyroid neoplasm	0.00% 0/159 • Up to 28 weeks	0.64% 1/157 • Up to 28 weeks
Reproductive system and breast disorders Menstruation irregular	0.63% 1/159 • Up to 28 weeks	0.00% 0/157 • Up to 28 weeks

Other adverse events

Measure	Linagliptin 5mg + Metformin n=159 participants at risk Patients treated with linagliptin 5mg and metformin IR (1500mg to 2000mg total daily dose)	Linagliptin 5mg n=157 participants at risk Patients treated with linagliptin 5mg
Gastrointestinal disorders Diarrhoea	5.7% 9/159 • Up to 28 weeks	1.9% 3/157 • Up to 28 weeks
Infections and infestations Urinary tract infection	6.3% 10/159 • Up to 28 weeks	8.9% 14/157 • Up to 28 weeks
Metabolism and nutrition disorders Dyslipidaemia	8.8% 14/159 • Up to 28 weeks	14.0% 22/157 • Up to 28 weeks
Metabolism and nutrition disorders Hyperglycaemia	3.1% 5/159 • Up to 28 weeks	12.7% 20/157 • Up to 28 weeks
Nervous system disorders Headache	6.3% 10/159 • Up to 28 weeks	4.5% 7/157 • Up to 28 weeks

Additional Information

Boehringer Ingelheim Call Center

Boehringer Ingelheim Pharmaceuticals

Phone: 1-800-243-0127

Email: clintriage.rdg@boehringer-ingelheim.com

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