ClinicalTrials.gg
Sign In
CompletedNCT02897349Updated Mar 25, 2020Results posted

Linagliptin Add-on to Insulin Background Therapy

A Phase 3 interventional study of placebo and linagliptin in Diabetes Mellitus, Type 2, sponsored by Boehringer Ingelheim. Completed at 25 sites in China. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2020-03-25.

Sponsored by Boehringer Ingelheim · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
206
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

To evaluate the efficacy and safety of linagliptin compared to placebo when added on to insulin therapy alone or in combination with metformin in Chinese patients with type 2 diabetes mellitus with insufficient glycaemic control

02

Conditions studied

  • Diabetes Mellitus, Type 2
03

In context

Diabetes Mellitus, Type 2

9,589 studies on the registry are indexed under Diabetes Mellitus, Type 2; 1,332 are open to participants now.

This study's enrollment of 206 is above the median of 81 across 7,713 interventional studies indexed under Diabetes Mellitus, Type 2.

Browse Diabetes Mellitus, Type 2 studies →

Lead sponsor

Boehringer Ingelheim is the lead sponsor of 2,297 studies on the registry; 56 are open to participants now.

Of its 166 completed or terminated interventional studies of FDA-regulated products, 121 (73%) have results posted.

Browse Boehringer Ingelheim studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  • Diagnosis of type 2 diabetes mellitus prior to informed consent.

  • Chinese male or female patients who are pre-treated with insulin alone or in combination with metformin:

    • With maximum insulin dose of \<= 1 unit/kg/day. Acceptable basal insulins could be insulin glargin, insulin detemir or NPH (neutral protamin hagedorn) insulin with duration of action up to 24 h; acceptable pre-mixed insulins could be preparations with 25/75 or 30/70 ratio, with once or twice daily posology only. The total insulin dose should not be changed by more than 10% of the baseline value within the 12 weeks prior to randomisation (Visit 3). Both human insulin \& insulin analogue are accepted.
    • If the patient is taking metformin, stable dose (at least 1500 mg daily) must be maintained for at least 12 weeks without dose adjustments prior to randomisation (Visit 3).
  • HbA1c fulfills the following criteria: >= 7.5 % to \<= 10.0 % at Visit 1.
  • Age >= 18 years at Visit 1.
  • BMI \<= 45 kg/m2 (Body Mass Index) at Visit 1.

  • Women of childbearing potential must be ready and able to use highly effective methods of birth control per ICH (International Conference on Harmonisation) M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria is provided in the patient information.

    • A woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile.
    • Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy.
  • Signed and dated written informed consent by date of Visit 1 in accordance with ICH-GCP (Good Clinical Practice) and local legislation

Exclusion criteria

Exclusion criteria:

  • Uncontrolled hyperglycaemic with a glucose level >240 mg/dl (>13.3 mmol/L) after an overnight fast during placebo run-in and confirmed by a second measurement (not on the same day).
  • Any other antidiabetic drug within 3 months prior to informed consent except those defined as background treatment via inclusion criterion 2.
  • Acute coronary syndrome (non-STEMI (ST Segment Elevation Myocardial Infarction), STEMI and unstable angina pectoris), stroke or TIA (Transient ischemic attack) within 3 months prior to informed consent.
  • Indication of liver disease, defined by serum levels of either ALT (Alanine aminotransferase) (SGPT (serum glutamic pyruvate transaminase )), AST (Aspartate aminotransferase) (SGOT (serum glutamic-oxaloacetic transaminase)), or alkaline phosphatase above 3 × upper limit of normal (ULN (upper limit of normal)) as determined during screening and/or run-in phase.
  • Any contraindications to metformin according to the local label for those patients that enter the study with metformin therapy as provided in ISF (Investigator Site File).
  • Bariatric surgery within the past two years and other gastrointestinal surgeries that induce chronic malabsorption.
  • Medical history of cancer (except for basal cell carcinoma) and/or treatment for cancer within the last 5 years.
  • Blood dyscrasias or any disorders causing hemolysis or unstable Red Blood Cell (e.g. malaria, babesiosis, haemolytic anemia).
  • Known hypersensitivity or allergy to the investigational product or its recipients.
  • Treatment with anti-obesity drugs 3 months prior to informed consent or any other treatment at the time of screening (i.e. surgery, aggressive diet regimen, etc.) leading to unstable body weight.
  • Current treatment with systemic steroids at time of informed consent or change in dosage of thyroid hormones within 6 weeks prior to informed consent or any other uncontrolled endocrine disorder except T2DM (Type 2 diabetes mellitus).
  • Women who are pregnant, nursing, or who plan to become pregnant while in the trial.
  • Alcohol or drug abuse within the 3 months prior to informed consent that would interfere with trial participation or any ongoing condition leading to a decreased compliance to study procedures or study drug intake in the opinion of the investigator.
  • Participation in another trial with an investigational drug within 2 months prior to informed consent or previous enrolment in this trial.
  • Any other clinical condition that would jeopardize patient's safety while participating in this clinical trial in the opinion of the investigator.
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double
Enrollment
206 participants (actual)

Study arms

  • Experimental
    linagliptin

    Drug: linagliptin · Drug: background therapy

  • Placebo comparator
    Placebo

    Drug: placebo · Drug: background therapy

Interventions

  • Drugplacebo
  • Druglinagliptin
  • Drugbackground therapy

    insulin with or without metformin

06

What researchers measure

Primary outcomes

  1. Percentage Change From Baseline in Glycosylated Haemoglobin A1c (HbA1c) After 24 Weeks of Treatment

    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.

    Time frame: Baseline and week 24

Secondary outcomes

  1. Change From Baseline in Fasting Plasma Glucose (FPG) After 24 Weeks of Treatment

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

    Time frame: Baseline and week 24

  2. Change From Baseline in 2-hour (2-h) Postprandial Plasma Glucose (PPG) After 24 Weeks of Treatment

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

    Time frame: Baseline and week 24

  3. Percentage of Participants With HbA1c on Treatment <7.0 Percentage (%) After 24 Weeks of Treatment

    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.

    Time frame: 24 weeks

  4. Percentage of Participants With HbA1c on Treatment < 6.5% After 24 Weeks of Treatment

    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.

    Time frame: 24 weeks

  5. Percentage of Participants With HbA1c Lowering by at Least 0.5% After 24 Weeks of Treatment

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

    Time frame: 24 weeks

  6. Percentage of Participants With Any Investigator-defined Hypoglycaemic Adverse Event (AE) With Plasma Glucose (PG) ≤70 mg/dL

    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.

    Time frame: 24 weeks

  7. Percentage of Participants With Any Severe Hypoglycaemic AE

    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.

    Time frame: 24 weeks

07

Results

Posted Jan 21, 2020

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.

Participant flow — Overall Study
MilestonePlacebo Matching LinagliptinLinagliptin
Started102104
Completed9798
Not completed56
Withdrew: Lost to follow-up22
Withdrew: Adverse event33
Withdrew: Other than listed above01

Outcome measures

PrimaryPercentage Change From Baseline in Glycosylated Haemoglobin A1c (HbA1c) After 24 Weeks of Treatment

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.

Time frame:
Baseline and week 24
Reported as:
Least squares mean · Percentage change
Percentage Change From Baseline in Glycosylated Haemoglobin A1c (HbA1c) After 24 Weeks of Treatment
Percentage changePlacebo Matching LinagliptinLinagliptin
Percentage Change From Baseline in Glycosylated Haemoglobin A1c (HbA1c) After 24 Weeks of Treatment-0.20 ± 0.09-0.61 ± 0.09
Statistical analysis
  • Placebo Matching Linagliptin vs Linagliptin · Mixed model repeated measures · p = 0.0016 · Adjusted mean difference (%): -0.40 · 95% CI -0.65 to -0.16
SecondaryChange From Baseline in Fasting Plasma Glucose (FPG) After 24 Weeks of Treatment

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

Time frame:
Baseline and week 24
Reported as:
Least squares mean · Milligram/Decilitre (mg/dL)
Change From Baseline in Fasting Plasma Glucose (FPG) After 24 Weeks of Treatment
Milligram/Decilitre (mg/dL)Placebo Matching LinagliptinLinagliptin
Change From Baseline in Fasting Plasma Glucose (FPG) After 24 Weeks of Treatment0.7 ± 3.6-5.5 ± 3.6
Statistical analysis
  • Placebo Matching Linagliptin vs Linagliptin · Mixed model repeated measures · p = 0.2241 · Adjusted mean difference (mg/dl): -6.2 · 95% CI -16.2 to 3.8
SecondaryChange From Baseline in 2-hour (2-h) Postprandial Plasma Glucose (PPG) After 24 Weeks of Treatment

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

Time frame:
Baseline and week 24
Reported as:
Least squares mean · mg/dL
Change From Baseline in 2-hour (2-h) Postprandial Plasma Glucose (PPG) After 24 Weeks of Treatment
mg/dLPlacebo Matching LinagliptinLinagliptin
Change From Baseline in 2-hour (2-h) Postprandial Plasma Glucose (PPG) After 24 Weeks of Treatment-0.06 ± 5.98-32.01 ± 5.66
Statistical analysis
  • Placebo Matching Linagliptin vs Linagliptin · ANCOVA · p = 0.0001 · Adjusted mean difference (mg/dl): -31.95 · 95% CI -48.15 to -15.75
SecondaryPercentage of Participants With HbA1c on Treatment <7.0 Percentage (%) After 24 Weeks of Treatment

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.

Time frame:
24 weeks
Reported as:
Number · Percentage of participants
Percentage of Participants With HbA1c on Treatment <7.0 Percentage (%) After 24 Weeks of Treatment
Percentage of participantsPlacebo Matching LinagliptinLinagliptin
Percentage of Participants With HbA1c on Treatment <7.0 Percentage (%) After 24 Weeks of Treatment8.213.9
Statistical analysis
  • Placebo Matching Linagliptin vs Linagliptin · Regression, Logistic · p = 0.2431 · Odds ratio (or): 1.793 · 95% CI 0.673 to 4.780
SecondaryPercentage of Participants With HbA1c on Treatment < 6.5% After 24 Weeks of Treatment

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.

Time frame:
24 weeks
Reported as:
Number · Percentage of participants
Percentage of Participants With HbA1c on Treatment < 6.5% After 24 Weeks of Treatment
Percentage of participantsPlacebo Matching LinagliptinLinagliptin
Percentage of Participants With HbA1c on Treatment < 6.5% After 24 Weeks of Treatment3.04.0
Statistical analysis
  • Placebo Matching Linagliptin vs Linagliptin · Regression, Logistic · p = 0.6235 · Odds ratio (or): 1.481 · 95% CI 0.309 to 7.105
SecondaryPercentage of Participants With HbA1c Lowering by at Least 0.5% After 24 Weeks of Treatment

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

Time frame:
24 weeks
Reported as:
Number · Percentage of participants
Percentage of Participants With HbA1c Lowering by at Least 0.5% After 24 Weeks of Treatment
Percentage of participantsPlacebo Matching LinagliptinLinagliptin
Percentage of Participants With HbA1c Lowering by at Least 0.5% After 24 Weeks of Treatment36.055.4
Statistical analysis
  • Placebo Matching Linagliptin vs Linagliptin · Regression, Logistic · p = 0.0049 · Odds ratio (or): 2.293 · 95% CI 1.286 to 4.091
SecondaryPercentage of Participants With Any Investigator-defined Hypoglycaemic Adverse Event (AE) With Plasma Glucose (PG) ≤70 mg/dL

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.

Time frame:
24 weeks
Reported as:
Number · Percentage of Participants
Percentage of Participants With Any Investigator-defined Hypoglycaemic Adverse Event (AE) With Plasma Glucose (PG) ≤70 mg/dL
Percentage of ParticipantsPlacebo Matching LinagliptinLinagliptin
Percentage of Participants With Any Investigator-defined Hypoglycaemic Adverse Event (AE) With Plasma Glucose (PG) ≤70 mg/dL7.810.6
SecondaryPercentage of Participants With Any Severe Hypoglycaemic AE

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.

Time frame:
24 weeks
Reported as:
Number · Percentage of Participants
Percentage of Participants With Any Severe Hypoglycaemic AE
Percentage of ParticipantsPlacebo Matching LinagliptinLinagliptin
Percentage of Participants With Any Severe Hypoglycaemic AE0.00.0

Adverse events

Collected over From first drug administration until 7 days after the last drug administration, up to 176 days.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Placebo Matching Linagliptin1/102 (1%)17/102 (16.7%)26/102 (25.5%)
Linagliptin0/104 (0%)10/104 (9.6%)33/104 (31.7%)
Most frequent serious events
Showing 10 of 33
Most frequent serious events
EventPlacebo Matching LinagliptinLinagliptin
CataractEye disorders2/1021/104
Diabetic neuropathyNervous system disorders0/1022/104
Angina pectorisCardiac disorders1/1020/104
Coronary artery diseaseCardiac disorders1/1020/104
Conductive deafnessEar and labyrinth disorders1/1020/104
Deafness neurosensoryEar and labyrinth disorders1/1020/104
OphthalmoplegiaEye disorders1/1020/104
PterygiumEye disorders1/1020/104
Abdominal discomfortGastrointestinal disorders1/1020/104
Drug-induced liver injuryHepatobiliary disorders1/1020/104
Most frequent other events
Most frequent other events
EventPlacebo Matching LinagliptinLinagliptin
HypoglycaemiaMetabolism and nutrition disorders13/10218/104
Upper respiratory tract infectionInfections and infestations13/10214/104
HyperuricaemiaMetabolism and nutrition disorders1/1026/104

Baseline characteristics

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

Age, Continuous
Age, Continuous(Years)Placebo Matching LinagliptinLinagliptinTotal
Mean57.1 ± 10.660.1 ± 9.558.7 ± 10.2
Sex: Female, Male
Sex: Female, Male(Participants)Placebo Matching LinagliptinLinagliptinTotal
Female4852100
Male5452106
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Placebo Matching LinagliptinLinagliptinTotal
Hispanic or Latino000
Not Hispanic or Latino102104206
Unknown or Not Reported000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Placebo Matching LinagliptinLinagliptinTotal
American Indian or Alaska Native000
Asian102104206
Native Hawaiian or Other Pacific Islander000
Black or African American000
White000
More than one race000
Unknown or Not Reported000
08

Study locations

25 sites
  • China-Japan Friendship Hospital
    Beijing, 100029, China
  • Beijing Tongren Hospital
    Beijing, 100730, China
  • The General Hospital of Chinese People's Armed Police Forces
    Beijing, 100854, China
  • First Hospital of Jilin University
    Changchun, 130021, China
  • No.900 Hospital of PLA Joint Logistics Support Force
    Fuzhou, 350025, China
  • Third Affiliated Hospital of Guangzhou Medical University
    Guangzhou, 510150, China
  • The Affiliated Hospital of Guizhou Medical University
    Guiyang, 550004, China
  • The Affiliated Hospital of Hangzhou Normal University
    Hangzhou, 310015, China
  • General Hospital of Jinan Military Area
    Jinan, 250000, China
  • Nanjing First Hospital
    Nanjing, 210006, China
  • The affiliated hospital of medicalcollege qingdao university
    Qingdao, 266005, China
  • Centre Hospital of Putuo District, Shanghai
    Shanghai, 200062, China
  • Shanghai Tenth People's Hospital
    Shanghai, 200072, China
  • Yangpu Hospital, Tongji University
    Shanghai, 200090, China
  • Second Hospital Affiliated to Shantou Medical University
    Shantou, 515041, China
  • Shengjing Hospital of China Medical University
    Shengyang, 110072, China
  • Siping Central People's Hospital
    Siping, 136000, China
  • The First Affiliated Hospital of Soochow University
    Suzhou, 215006, China
  • Nankai University Affiliated Hospital
    Tianjin, 300000, China
  • The 2nd Hospital of Tianjin Medical University
    Tianjin, 300000, China
  • Tianjin Medical University General Hospital
    Tianjin, 30052, China
  • Renmin Hospital of Wuhan University
    Wuhan, 430060, China
  • First Affiliated Hospital of Xiamen University
    Xiamen, 361003, China
  • the first people hospital of Yue Yang
    Yueyang, 414000, China
  • Affiliated Hospital of Jiangsu University
    Zhenjiang, 212013, China
09

References and documents

Related links

Study documents

  • Statistical analysis plan · Feb 14, 2019
  • Study protocol · Nov 28, 2017

Documents are hosted by the registry — open the source record to download them.

10

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reachedSimilar studies: half by the dot; the band is the middle halfHalf of similar studies reached it by the dot; the band is the middle half, from a quarter to three quarters

Ran from Sep 2016 to primary completion in Jan 2019, 27 months.

Results were first posted in Jan 2020, 1 year after primary completion.

Of 430 industry-sponsored phase 3 interventional studies under Diabetes Mellitus, Type 2, half reached primary completion within 19 months of starting (the median), counting those still running; a quarter within 14 and three quarters within 26. This study's 27 months is above that.

Counting every sponsor, half of 510 studies reached it within 20 months; a quarter within 14 and three quarters within 30.

How these figures are worked out, and which studies are left out of them.

Registered
Aug 30, 2016
First posted
Sep 13, 2016
StartActual
Sep 30, 2016
Primary completionActual
Jan 11, 2019
CompletionActual
Jan 18, 2019
Results first posted
Jan 21, 2020
Last update
Mar 25, 2020
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Mar 25, 2020, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT02897349
Lead sponsor
Boehringer Ingelheim
Collaborators
Eli Lilly and Company
Responsible party
Sponsor
First posted
Sep 13, 2016
Start date
Sep 30, 2016
Primary completion
Jan 11, 2019
Completion
Jan 18, 2019
Results posted
Jan 21, 2020
Last update
Mar 25, 2020

Study contacts

Boehringer Ingelheim
study chair · Boehringer Ingelheim
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Mar 2020. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Studies of the drug tested here: Linagliptin

Other studies in this condition

Diabetes Mellitus, Type 2 →

Other studies from this sponsor

Boehringer Ingelheim →

Start the discussion