Trial Outcomes & Findings for Linagliptin Add-on to Insulin Background Therapy (NCT NCT02897349)

Last Updated: 2020-03-25

Results Overview

Percentage change from baseline, that is, \[\[(HbA1c after 24 weeks of treatment) - (HbA1c at baseline)\] / (HbA1c at baseline)\] \*100%, where baseline refers to the last observation prior to the start of randomised study drug, including the observation prior to the placebo run-in.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

206 participants

Primary outcome timeframe

Baseline and week 24

Results posted on

2020-03-25

Participant Flow

This was a randomised, double-blind, multi-centre, and placebo-controlled, parallel group study to compare linagliptin with placebo as add-on therapy to stable insulin alone (basal insulin, premixed insulin) or in combination with metformin in Chinese type 2 diabetes mellitus (T2DM) participants with insufficient glycaemic control.

All participants were screened for eligibility to participate in the trial. Participants attended specialist sites which would then ensure that all participants met all inclusion/exclusion criteria. Participants were not to be randomized to trial treatment if any one of the specific entry criteria were not met.

Participant milestones

Participant milestones
Measure	Placebo Matching Linagliptin Participants were administered placebo matching 5 milligram (mg) linagliptin tablet once daily per os (p.o.) for 24 weeks.	Linagliptin Participants were administered 5 milligram (mg) linagliptin tablet once daily per os (p.o.) for 24 weeks.
Overall Study STARTED	102	104
Overall Study COMPLETED	97	98
Overall Study NOT COMPLETED	5	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Matching Linagliptin Participants were administered placebo matching 5 milligram (mg) linagliptin tablet once daily per os (p.o.) for 24 weeks.	Linagliptin Participants were administered 5 milligram (mg) linagliptin tablet once daily per os (p.o.) for 24 weeks.
Overall Study Lost to Follow-up	2	2
Overall Study Adverse Event	3	3
Overall Study Other than listed above	0	1

Baseline Characteristics

Linagliptin Add-on to Insulin Background Therapy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo Matching Linagliptin n=102 Participants Participants were administered placebo matching 5 milligram (mg) linagliptin tablet once daily per os (p.o.) for 24 weeks.	Linagliptin n=104 Participants Participants were administered 5 milligram (mg) linagliptin tablet once daily per os (p.o.) for 24 weeks.	Total n=206 Participants Total of all reporting groups
Age, Continuous	57.1 Years STANDARD_DEVIATION 10.6 • n=5 Participants	60.1 Years STANDARD_DEVIATION 9.5 • n=7 Participants	58.7 Years STANDARD_DEVIATION 10.2 • n=5 Participants
Sex: Female, Male Female	48 Participants n=5 Participants	52 Participants n=7 Participants	100 Participants n=5 Participants
Sex: Female, Male Male	54 Participants n=5 Participants	52 Participants n=7 Participants	106 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	102 Participants n=5 Participants	104 Participants n=7 Participants	206 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	102 Participants n=5 Participants	104 Participants n=7 Participants	206 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and week 24

Population: Full analysis set (FAS) observed cases (OC): The FAS consisted of all patients randomised in the TS who had a baseline HbA1c value and at least one on-treatment HbA1c value. The FAS was the basis for the intention-to-treat (ITT) analysis.

Outcome measures

Outcome measures
Measure	Placebo Matching Linagliptin n=99 Participants Participants were administered placebo matching 5 milligram (mg) linagliptin tablet once daily per os (p.o.) for 24 weeks.	Linagliptin n=100 Participants Participants were administered 5 milligram (mg) linagliptin tablet once daily per os (p.o.) for 24 weeks.
Percentage Change From Baseline in Glycosylated Haemoglobin A1c (HbA1c) After 24 Weeks of Treatment	-0.20 Percentage change Standard Error 0.09	-0.61 Percentage change Standard Error 0.09

SECONDARY outcome

Timeframe: Baseline and week 24

Population: FAS (OC)

Change from baseline in Fasting plasma glucose (FPG) after 24 weeks of treatment.

Outcome measures

Outcome measures
Measure	Placebo Matching Linagliptin n=99 Participants Participants were administered placebo matching 5 milligram (mg) linagliptin tablet once daily per os (p.o.) for 24 weeks.	Linagliptin n=99 Participants Participants were administered 5 milligram (mg) linagliptin tablet once daily per os (p.o.) for 24 weeks.
Change From Baseline in Fasting Plasma Glucose (FPG) After 24 Weeks of Treatment	0.7 Milligram/Decilitre (mg/dL) Standard Error 3.6	-5.5 Milligram/Decilitre (mg/dL) Standard Error 3.6

SECONDARY outcome

Timeframe: Baseline and week 24

Population: Meal tolerance test (MTT) (OC) set: MTT-set consisted all patients of the FAS with a valid MTT at baseline and at the end of the study. An MTT was considered valid if it had a valid FPG and a valid 2-h PPG value.

Change from baseline in 2-hour (2-h) postprandial plasma glucose (PPG) after 24 weeks of treatment.

Outcome measures

Outcome measures
Measure	Placebo Matching Linagliptin n=78 Participants Participants were administered placebo matching 5 milligram (mg) linagliptin tablet once daily per os (p.o.) for 24 weeks.	Linagliptin n=88 Participants Participants were administered 5 milligram (mg) linagliptin tablet once daily per os (p.o.) for 24 weeks.
Change From Baseline in 2-hour (2-h) Postprandial Plasma Glucose (PPG) After 24 Weeks of Treatment	-0.06 mg/dL Standard Error 5.98	-32.01 mg/dL Standard Error 5.66

SECONDARY outcome

Timeframe: 24 weeks

Population: Full analysis set (FAS) Non-completers considered as failure (NCF)

Percentage of participants with HbA1c on treatment \<7.0 percentage (%) after 24 weeks of treatment. Participants with baseline HbA1c \<7.0% were excluded from the analysis.

Outcome measures

Outcome measures
Measure	Placebo Matching Linagliptin n=97 Participants Participants were administered placebo matching 5 milligram (mg) linagliptin tablet once daily per os (p.o.) for 24 weeks.	Linagliptin n=101 Participants Participants were administered 5 milligram (mg) linagliptin tablet once daily per os (p.o.) for 24 weeks.
Percentage of Participants With HbA1c on Treatment <7.0 Percentage (%) After 24 Weeks of Treatment	8.2 Percentage of participants	13.9 Percentage of participants

SECONDARY outcome

Timeframe: 24 weeks

Population: FAS (NCF)

Percentage of participants with HbA1c on treatment \< 6.5% after 24 weeks of treatment. Participants with baseline HbA1c \<6.5% were excluded from the analysis.

Outcome measures

Outcome measures
Measure	Placebo Matching Linagliptin n=100 Participants Participants were administered placebo matching 5 milligram (mg) linagliptin tablet once daily per os (p.o.) for 24 weeks.	Linagliptin n=101 Participants Participants were administered 5 milligram (mg) linagliptin tablet once daily per os (p.o.) for 24 weeks.
Percentage of Participants With HbA1c on Treatment < 6.5% After 24 Weeks of Treatment	3.0 Percentage of participants	4.0 Percentage of participants

SECONDARY outcome

Timeframe: 24 weeks

Population: FAS (NCF)

Percentage of participants with HbA1c lowering by at least 0.5% after 24 weeks of treatment.

Outcome measures

Outcome measures
Measure	Placebo Matching Linagliptin n=100 Participants Participants were administered placebo matching 5 milligram (mg) linagliptin tablet once daily per os (p.o.) for 24 weeks.	Linagliptin n=101 Participants Participants were administered 5 milligram (mg) linagliptin tablet once daily per os (p.o.) for 24 weeks.
Percentage of Participants With HbA1c Lowering by at Least 0.5% After 24 Weeks of Treatment	36.0 Percentage of participants	55.4 Percentage of participants

SECONDARY outcome

Timeframe: 24 weeks

Population: Treated set (TS) : The TS consisted of all patients treated with at least one dose of study drug.

Incidence of investigator-reported hypoglycaemic events confirmed by a measured blood glucose ≤70 mg/dL (≤3.9 Millimoles Per Litre (mmol/L)). Severe hypoglycaemic AE = hypoglycaemic event requiring the assistance of another person to actively administer carbohydrate, glucagon or other resuscitative actions.

Outcome measures

Outcome measures
Measure	Placebo Matching Linagliptin n=102 Participants Participants were administered placebo matching 5 milligram (mg) linagliptin tablet once daily per os (p.o.) for 24 weeks.	Linagliptin n=104 Participants Participants were administered 5 milligram (mg) linagliptin tablet once daily per os (p.o.) for 24 weeks.
Percentage of Participants With Any Investigator-defined Hypoglycaemic Adverse Event (AE) With Plasma Glucose (PG) ≤70 mg/dL	7.8 Percentage of Participants	10.6 Percentage of Participants

SECONDARY outcome

Timeframe: 24 weeks

Population: TS

Incidence of severe hypoglycaemic events (requiring active assistance by another person, or fatal). Severe hypoglycaemic AE = hypoglycaemic event requiring the assistance of another person to actively administer carbohydrate, glucagon or other resuscitative actions.

Outcome measures

Outcome measures
Measure	Placebo Matching Linagliptin n=102 Participants Participants were administered placebo matching 5 milligram (mg) linagliptin tablet once daily per os (p.o.) for 24 weeks.	Linagliptin n=104 Participants Participants were administered 5 milligram (mg) linagliptin tablet once daily per os (p.o.) for 24 weeks.
Percentage of Participants With Any Severe Hypoglycaemic AE	0.0 Percentage of Participants	0.0 Percentage of Participants

Adverse Events

Placebo Matching Linagliptin

Serious events: 17 serious events

Other events: 26 other events

Deaths: 1 deaths

Linagliptin

Serious events: 10 serious events

Other events: 33 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo Matching Linagliptin n=102 participants at risk Participants were administered placebo matching 5 milligram (mg) linagliptin tablet once daily per os (p.o.) for 24 weeks.	Linagliptin n=104 participants at risk Participants were administered 5 milligram (mg) linagliptin tablet once daily per os (p.o.) for 24 weeks.
Infections and infestations Upper respiratory tract infection	12.7% 13/102 • From first drug administration until 7 days after the last drug administration, up to 176 days.	13.5% 14/104 • From first drug administration until 7 days after the last drug administration, up to 176 days.
Metabolism and nutrition disorders Hyperuricaemia	0.98% 1/102 • From first drug administration until 7 days after the last drug administration, up to 176 days.	5.8% 6/104 • From first drug administration until 7 days after the last drug administration, up to 176 days.
Metabolism and nutrition disorders Hypoglycaemia	12.7% 13/102 • From first drug administration until 7 days after the last drug administration, up to 176 days.	17.3% 18/104 • From first drug administration until 7 days after the last drug administration, up to 176 days.

Additional Information

Boehringer Ingelheim, Call Center

Boehringer Ingelheim

Phone: 1-800-243-0127

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo Matching Linagliptin n=102 participants at risk Participants were administered placebo matching 5 milligram (mg) linagliptin tablet once daily per os (p.o.) for 24 weeks.	Linagliptin n=104 participants at risk Participants were administered 5 milligram (mg) linagliptin tablet once daily per os (p.o.) for 24 weeks.
Cardiac disorders Angina pectoris	0.98% 1/102 • From first drug administration until 7 days after the last drug administration, up to 176 days.	0.00% 0/104 • From first drug administration until 7 days after the last drug administration, up to 176 days.
Cardiac disorders Angina unstable	0.00% 0/102 • From first drug administration until 7 days after the last drug administration, up to 176 days.	0.96% 1/104 • From first drug administration until 7 days after the last drug administration, up to 176 days.
Cardiac disorders Bundle branch block left	0.00% 0/102 • From first drug administration until 7 days after the last drug administration, up to 176 days.	0.96% 1/104 • From first drug administration until 7 days after the last drug administration, up to 176 days.
Cardiac disorders Coronary artery disease	0.98% 1/102 • From first drug administration until 7 days after the last drug administration, up to 176 days.	0.00% 0/104 • From first drug administration until 7 days after the last drug administration, up to 176 days.
Ear and labyrinth disorders Conductive deafness	0.98% 1/102 • From first drug administration until 7 days after the last drug administration, up to 176 days.	0.00% 0/104 • From first drug administration until 7 days after the last drug administration, up to 176 days.
Ear and labyrinth disorders Deafness neurosensory	0.98% 1/102 • From first drug administration until 7 days after the last drug administration, up to 176 days.	0.00% 0/104 • From first drug administration until 7 days after the last drug administration, up to 176 days.
Eye disorders Cataract	2.0% 2/102 • From first drug administration until 7 days after the last drug administration, up to 176 days.	0.96% 1/104 • From first drug administration until 7 days after the last drug administration, up to 176 days.
Eye disorders Ophthalmoplegia	0.98% 1/102 • From first drug administration until 7 days after the last drug administration, up to 176 days.	0.00% 0/104 • From first drug administration until 7 days after the last drug administration, up to 176 days.
Eye disorders Pterygium	0.98% 1/102 • From first drug administration until 7 days after the last drug administration, up to 176 days.	0.00% 0/104 • From first drug administration until 7 days after the last drug administration, up to 176 days.
Gastrointestinal disorders Abdominal discomfort	0.98% 1/102 • From first drug administration until 7 days after the last drug administration, up to 176 days.	0.00% 0/104 • From first drug administration until 7 days after the last drug administration, up to 176 days.
Gastrointestinal disorders Large intestine polyp	0.00% 0/102 • From first drug administration until 7 days after the last drug administration, up to 176 days.	0.96% 1/104 • From first drug administration until 7 days after the last drug administration, up to 176 days.
Gastrointestinal disorders Obstructive pancreatitis	0.00% 0/102 • From first drug administration until 7 days after the last drug administration, up to 176 days.	0.96% 1/104 • From first drug administration until 7 days after the last drug administration, up to 176 days.
Hepatobiliary disorders Cholecystitis acute	0.00% 0/102 • From first drug administration until 7 days after the last drug administration, up to 176 days.	0.96% 1/104 • From first drug administration until 7 days after the last drug administration, up to 176 days.
Hepatobiliary disorders Cholelithiasis	0.00% 0/102 • From first drug administration until 7 days after the last drug administration, up to 176 days.	0.96% 1/104 • From first drug administration until 7 days after the last drug administration, up to 176 days.
Hepatobiliary disorders Drug-induced liver injury	0.98% 1/102 • From first drug administration until 7 days after the last drug administration, up to 176 days.	0.00% 0/104 • From first drug administration until 7 days after the last drug administration, up to 176 days.
Hepatobiliary disorders Liver injury	0.98% 1/102 • From first drug administration until 7 days after the last drug administration, up to 176 days.	0.00% 0/104 • From first drug administration until 7 days after the last drug administration, up to 176 days.
Injury, poisoning and procedural complications Fall	0.00% 0/102 • From first drug administration until 7 days after the last drug administration, up to 176 days.	0.96% 1/104 • From first drug administration until 7 days after the last drug administration, up to 176 days.
Injury, poisoning and procedural complications Humerus fracture	0.00% 0/102 • From first drug administration until 7 days after the last drug administration, up to 176 days.	0.96% 1/104 • From first drug administration until 7 days after the last drug administration, up to 176 days.
Injury, poisoning and procedural complications Patella fracture	0.98% 1/102 • From first drug administration until 7 days after the last drug administration, up to 176 days.	0.00% 0/104 • From first drug administration until 7 days after the last drug administration, up to 176 days.
Injury, poisoning and procedural complications Road traffic accident	0.98% 1/102 • From first drug administration until 7 days after the last drug administration, up to 176 days.	0.00% 0/104 • From first drug administration until 7 days after the last drug administration, up to 176 days.
Injury, poisoning and procedural complications Subcutaneous haematoma	0.98% 1/102 • From first drug administration until 7 days after the last drug administration, up to 176 days.	0.00% 0/104 • From first drug administration until 7 days after the last drug administration, up to 176 days.
Injury, poisoning and procedural complications Subdural haematoma	0.98% 1/102 • From first drug administration until 7 days after the last drug administration, up to 176 days.	0.00% 0/104 • From first drug administration until 7 days after the last drug administration, up to 176 days.
Metabolism and nutrition disorders Diabetes mellitus inadequate control	0.98% 1/102 • From first drug administration until 7 days after the last drug administration, up to 176 days.	0.00% 0/104 • From first drug administration until 7 days after the last drug administration, up to 176 days.
Metabolism and nutrition disorders Diabetic ketoacidosis	0.00% 0/102 • From first drug administration until 7 days after the last drug administration, up to 176 days.	0.96% 1/104 • From first drug administration until 7 days after the last drug administration, up to 176 days.
Nervous system disorders Cerebral infarction	0.98% 1/102 • From first drug administration until 7 days after the last drug administration, up to 176 days.	0.00% 0/104 • From first drug administration until 7 days after the last drug administration, up to 176 days.
Nervous system disorders Cerebral ischaemia	0.98% 1/102 • From first drug administration until 7 days after the last drug administration, up to 176 days.	0.00% 0/104 • From first drug administration until 7 days after the last drug administration, up to 176 days.
Nervous system disorders Diabetic neuropathy	0.00% 0/102 • From first drug administration until 7 days after the last drug administration, up to 176 days.	1.9% 2/104 • From first drug administration until 7 days after the last drug administration, up to 176 days.
Nervous system disorders Facial paralysis	0.98% 1/102 • From first drug administration until 7 days after the last drug administration, up to 176 days.	0.00% 0/104 • From first drug administration until 7 days after the last drug administration, up to 176 days.
Renal and urinary disorders Acute kidney injury	0.00% 0/102 • From first drug administration until 7 days after the last drug administration, up to 176 days.	0.96% 1/104 • From first drug administration until 7 days after the last drug administration, up to 176 days.
Renal and urinary disorders Diabetic nephropathy	0.00% 0/102 • From first drug administration until 7 days after the last drug administration, up to 176 days.	0.96% 1/104 • From first drug administration until 7 days after the last drug administration, up to 176 days.
Renal and urinary disorders Glomerulonephritis chronic	0.00% 0/102 • From first drug administration until 7 days after the last drug administration, up to 176 days.	0.96% 1/104 • From first drug administration until 7 days after the last drug administration, up to 176 days.
Renal and urinary disorders Nephrolithiasis	0.98% 1/102 • From first drug administration until 7 days after the last drug administration, up to 176 days.	0.00% 0/104 • From first drug administration until 7 days after the last drug administration, up to 176 days.
Vascular disorders Hypertension	0.98% 1/102 • From first drug administration until 7 days after the last drug administration, up to 176 days.	0.00% 0/104 • From first drug administration until 7 days after the last drug administration, up to 176 days.