Primary outcomeNumber· week 12, week 24
Percentage of Patients Whose Glycosylated Haemoglobin (HbA1c) <7% at the End of the Comparative Period
| Group | Value (percentage of participants) |
|---|---|
| Insulin Glargine | 48.4 |
| Liraglutide | 45.9 |
Trial · Interventional
CompletedPhase 4Results postedRegistry dataEfficacy Assessment of Insulin Glargine Versus LiraglutidE After Oral Agents Failure
Short name EAGLE
NCTNCT01117350 (opens ClinicalTrials.gov in a new tab)Other idLANTU_C_03680Other id2010-018437-21Other idU1111-1116-9684
Overview
- Status
- Completed
- Phase
- Phase 4
- Enrollment
- 978 participants (actual)
- Sponsor
- Sanofi · Industry
- Design
- Randomized · Open label (no masking)
- Countries
17 countries
United States, Austria, Brazil, Canada, Czechia, Finland, France, Greece, Ireland, Israel, Mexico, Netherlands, Russia, Slovakia, Spain, Sweden, Turkey (Türkiye)
- Start
- Jul 2010
- Primary completion
- Oct 2012
- Completion
- Mar 2013
- First posted
- 5 May 2010 (estimated)
- Last update posted
- 11 Apr 2014 (estimated)
- Conditions
- Diabetes Mellitus, Type 2
Timeline
1 trial · 1 completed · 1 with posted results
- Completed
- Ongoing
- Not yet recruiting
- Stopped
- Estimated dates (est.)
- Results posted
20102011201220132014
- Ph 4
Registry summary
Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.
Primary objective: To demonstrate the superiority of insulin glargine over liraglutide in terms of percentage of patients reaching a Glycosylated Haemoglobin (HbA1c) \< 7% at the end of the comparative period (24 weeks) in Type 2 diabetic patients failing lifestyle management and oral agents Secondary objectives of the comparative period (24 weeks): \>To assess the effect of insulin glargine in comparison with liraglutide on: * HbA1c level * Percentage of patients whose HbA1c has decreased but remains \>= 7% at the end of the comparative period * Percentage of patients whose HbA1c has increased at the end of the comparative period * Fasting Plasma Glucose (FPG) * 7-point Plasma Glucose (PG) profiles * Hypoglycemia occurrence * Body weight * Adverse events Objectives of the extension period (24 weeks): \>To assess the effect of insulin glargine in patients not adequately controlled with liraglutide on: * HbA1c level * FPG * 7-point PG profiles * Hypoglycemia occurrence * Body weight * Adverse events
Interventions
- Insulin glargineDrug
- LiraglutideDrug
- MetforminDrug
Arms2
Experimental
Insulin Glargine
Insulin glargine administered once a day, in the morning or in the evening, at the most convenient time. The time of injection, once chosen was to remain unchanged during the whole duration of the study. The starting dose was 0.2 Unit per kilogram of body weight or 10 Units. Patients were empowered to adjust their insulin doses, under strict investigator's supervision. Insulin titration (by 2 or 4 Units) was done every 3 days according to the median value of Fasting Plasma Glucose (FPG) of the last 3 days. The goal was to achieve 70 \< FPG ≤ 100 mg/dL (3.9 \< FPG ≤ 5.5 mmol/L). Minor deviations from the titration scheme could be allowed, based on Investigator's judgment and patient's situation.
Active comparator
Liraglutide
Liraglutide administered once a day, in the morning or in the evening, at the most convenient time. The time of injection , once chosen was to remain unchanged during the whole duration of the study. The dose was 0.6 mg/day during the first week, 1.2 mg/day during the second week and 1.8 mg/day until week 24. The dose might be decreased to 1.2 mg for safety reasons (e.g. gastro-intestinal tolerability), based on Investigator's judgment.
Primary outcomes1
Outcomes the sponsor listed as primary.
Percentage of Patients Whose Glycosylated Haemoglobin (HbA1c) <7% at the End of the Comparative Period
Time frame · week 12, week 24
Registry description
The value at the end of the comparative period was defined as the last available HbA1c value measured during the comparative period plus 14 days after the last dose of Investigational Product (i.e. last-observation-carried-forward \[LOCF\] value).
Secondary outcomes(16)
Percentage of Patients Whose Glycosylated Haemoglobin (HbA1c) Has Decreased But Remains ≥7% at the End of the Comparative Period
Time frame · baseline (week -2), week 12, week 24
Registry description
Percentage of patients with: \* HbA1c value at end of the comparative period (LOCF) lower than HbA1c baseline value AND \* HbA1c value at end of the comparative period (LOCF) ≥7%
Percentage of Patients Whose Glycosylated Haemoglobin (HbA1c) Has Increased at the End of the Comparative Period
Time frame · baseline (week -2), week 12, week 24
Registry description
Percentage of patients with HbA1c value at end of the comparative period (LOCF) higher than HbA1c baseline value
Glycosylated Haemoglobin (HbA1c): Change From Baseline to the End of Comparative Period
Time frame · baseline (week -2), week 12, week 24
Registry description
Change in HbA1C from baseline to the last observation carried forward (LOCF) measured during the comparative period = LOCF value - baseline value
Glycosylated Haemoglobin (HbA1c): Change From Beginning to the End of the Extension Period
Time frame · week 24, week 36, week 48
Registry description
Change in HbA1C from beginning of the extension period (week 24) to the last observation carried forward (LOCF) measured during the extension period = LOCF value - week 24 value
Percentage of Patients Whose Glycosylated Haemoglobin (HbA1c) <7% at the End of the Extension Period
Time frame · week 36, week 48
Registry description
Value at the end of the extension period defined as last available HbA1c value measured during the extension period (i.e. last observation carried forward (LOCF) value)
Self-Monitored Fasting Plasma Glucose (SMFPG) Measurements: Change From Baseline to the End of the Comparative Period
Time frame · baseline (week 0), week 6, week 12, week 18, week 24
Registry description
SMFPG = mean value of Self-Monitored Fasting Plasma Glucose measurements over 3 consecutive days in the week before each visit Value at the end of the comparative period defined as last available value during the comparative period (i.e. last-observation-carried-forward \[LOCF\] value) Change = LOCF value - baseline value
Self-Monitored Fasting Plasma Glucose (SMFPG) Measurements: Change From Beginning to the End of the Extension Period
Time frame · week 24, week 30, week 36, week 48
Registry description
SMFPG = mean value of Self-Monitored Fasting Plasma Glucose measurements over 3 consecutive days in the week before each visit Value at the end of the extension period defined as last available value during the extension period (i.e. last-observation-carried-forward \[LOCF\] value) Change = LOCF value - week 24 value
Self-Monitored 7-point Plasma Glucose (PG) Profile: Change From Baseline to the End of the Comparative Period
Time frame · baseline (week 0), week 12, week 24
Registry description
Self-monitored 7-point plasma glucose profiles (before and 2 hours after the start of breakfast, lunch and dinner, and at bedtime) recorded on 3 consecutive days in the week before each visit Value at the end of the comparative period defined as last available value during the comparative period (i.e. last-observation-carried-forward \[LOCF\] value) Change = LOCF value - baseline value
Self-Monitored 7-point Plasma Glucose (PG) Profile: Change From Beginning to the End of the Extension Period
Time frame · week 24, week 36, week 48
Registry description
Self-monitored 7-point plasma glucose profiles (before and 2 hours after the start of breakfast, lunch and dinner, and at bedtime) recorded on 3 consecutive days in the week before each visit Value at the end of the extension period defined as last available value during the extension period (i.e. last-observation-carried-forward \[LOCF\] value) Change = LOCF value - week 24 value
Body Weight: Change From Baseline to the End of the Comparative Period
Time frame · baseline (week 0), week 2, week 6, week 12, week 18, week 24
Registry description
Change = Last weight value measured during the comparative period (LOCF value) - weight value at baseline
Body Weight: Change From Beginning to End of the Extension Period
Time frame · week 24, week 30, week 36, week 48
Registry description
Change = Last weight value measured during the extension period (LOCF value) - weight value at beginning of the Extension Period (Week 24)
Daily Dose of Insulin Glargine
Time frame · week 1, week 2, week 6, week 12, week 24
Daily Dose of Liraglutide
Time frame · week 1, week 2, week 6, week 12, week 24
Daily Dose of Insulin Glargine Administered During the Extension Period
Time frame · week 30, week 36, week 48
Hypoglycemia Occurence: Number of Patients With at Least One Episode of Symptomatic / Severe Symptomatic Hypoglycemia During the Comparative Period
Time frame · all across the comparative period (from week 0 to week 24)
Registry description
Symptomatic hypoglycemia was defined as an event with clinical symptoms that were considered to result from hypoglycemia. Severe symptomatic hypoglycemia was defined as an event with clinical symptoms that were considered to result from hypoglycemia, requiring the assistance of another person for active administration of carbohydrate, glucagon or other countermeasure because the patient could not treat him/herself due to acute neurological impairment directly resulting from the hypoglycemia (assistance by another person when the patient could have treated him/herself was not considered as requiring assistance)and one of the following criteria: * The event was associated with a measured PG level \< 36 mg/dL (2 mmol/L), * Or, in absence of PG value, the event was associated with neurological recovery attributable to the restoration of PG to normal, after oral carbohydrate, intravenous glucose or glucagon administration.
Hypoglycemia Occurence: Number of Patients With at Least One Episode of Symptomatic / Severe Symptomatic Hypoglycemia During the Extension Period
Time frame · all across the extension period (from week 24 to week 48)
Registry description
Symptomatic hypoglycemia was defined as an event with clinical symptoms that were considered to result from hypoglycemia. Severe symptomatic hypoglycemia was defined as an event with clinical symptoms that were considered to result from hypoglycemia, requiring the assistance of another person for active administration of carbohydrate, glucagon or other countermeasure because the patient could not treat him/herself due to acute neurological impairment directly resulting from the hypoglycemia (assistance by another person when the patient could have treated him/herself was not considered as requiring assistance)and one of the following criteria: * The event was associated with a measured PG level \< 36 mg/dL (2 mmol/L), * Or, in absence of PG value, the event was associated with neurological recovery attributable to the restoration of PG to normal, after oral carbohydrate, intravenous glucose or glucagon administration.
Posted results
Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.
Primary outcome results
Secondary and other outcome results(7)
Secondary outcomeNumber· baseline (week -2), week 12, week 24
Percentage of Patients Whose Glycosylated Haemoglobin (HbA1c) Has Decreased But Remains ≥7% at the End of the Comparative Period
| Group | Value (percentage of participants) |
|---|---|
| Insulin Glargine | 47.1 |
| Liraglutide | 46.3 |
Secondary outcomeNumber· baseline (week -2), week 12, week 24
Percentage of Patients Whose Glycosylated Haemoglobin (HbA1c) Has Increased at the End of the Comparative Period
| Group | Value (percentage of participants) |
|---|---|
| Insulin Glargine | 4.1 |
| Liraglutide | 6.6 |
Secondary outcomeMean· baseline (week -2), week 12, week 24
Glycosylated Haemoglobin (HbA1c): Change From Baseline to the End of Comparative Period
| Group | Value (percent) | Spread |
|---|---|---|
| Insulin Glargine | -1.92 | 1.22 |
| Liraglutide | -1.81 | 1.33 |
Secondary outcomeMean· week 24, week 36, week 48
Glycosylated Haemoglobin (HbA1c): Change From Beginning to the End of the Extension Period
| Group | Value (percent) | Spread |
|---|---|---|
| Insulin Glargine (Extension Period) | -0.26 | 1.11 |
Secondary outcomeNumber· week 36, week 48
Percentage of Patients Whose Glycosylated Haemoglobin (HbA1c) <7% at the End of the Extension Period
| Group | Value (percentage of participants) |
|---|---|
| Insulin Glargine (Extension Period) | 22.7 |
Secondary outcomeMean· baseline (week 0), week 6, week 12, week 18, week 24
Self-Monitored Fasting Plasma Glucose (SMFPG) Measurements: Change From Baseline to the End of the Comparative Period
| Group | Value (mg/dL) | Spread |
|---|---|---|
| Insulin Glargine | -65.25 | 50.95 |
| Liraglutide | -37.23 | 47.31 |
Secondary outcomeMean· week 24, week 30, week 36, week 48
Self-Monitored Fasting Plasma Glucose (SMFPG) Measurements: Change From Beginning to the End of the Extension Period
| Group | Value (mg/dL) | Spread |
|---|---|---|
| Insulin Glargine (Extension Period) | -44.63 | 45.47 |
Adverse events, as posted
| Group | Deaths | Serious events | Other events |
|---|---|---|---|
| Comparative Period: Insulin GlargineInsulin glargine starting dose: 0.2 Unit per kilogram of body weight or 10 Units. Insulin titration (by 2 or 4 Units) every 3 days according to the median value of Fast Plasma Glucose of the last 3 days | – | 11 / 484 | 92 / 484 |
| Comparative Period: LiraglutideLiraglutide dose: 0.6 mg/day during the first week, 1.2 mg/day during the second week and 1.8 mg/day until week 24 (comparative period) | – | 15 / 481 | 239 / 481 |
| Extension Period: Insulin GlargineFollowing a treatment with liraglutide during the comparative period, those patients have received insulin glargine during the extension period. Insulin glargine starting dose: 0.2 Unit per kilogram of body weight or 10 Units. Insulin titration (by 2 or 4 Units) every 3 days according to the median value of Fast Plasma Glucose of the last 3 days | – | 5 / 160 | 22 / 160 |
Each cell reads participants affected / participants at risk, as the registry posted them.
Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works
Studies0
Studies that cite this trial.
No study cites this trial.
Eligibility
Who could join, as posted.
- Sex
- All
- Age
- from 35 Years up to 75 Years
- Healthy volunteers
- Not accepted
Inclusion and exclusion criteria, as posted
Inclusion criteria (comparative period):
* Patients With Type 2 Diabetes diagnosed for at least 1 year,
* Treated with lifestyle interventions and metformin at the maximum tolerated dosage (with a minimum daily dosage of 1g), either alone or in combination with an oral insulin secretagogue (sulfonylurea, glinide or DiPeptidyl Peptidase IV inhibitor), for more than 3 months,
* 7.5% \< HbA1c \<= 12%,
* Body Mass Index (BMI) between 25 and 40 kg/m2 inclusively,
* Ability and willingness to perform PG (Plasma Glucose) self monitoring using the sponsor-provided glucose meter and to complete the patient diary,
* Willingness and ability to comply with the study protocol,
* Signed informed consent obtained prior to any study procedure.
Inclusion criteria (extension period):
* Patients treated with liraglutide (at the maximal tolerated dosage), having a mean FPG ≥ 250 mg/dL at visit 10 (Week 12) or visit 11 (Week 18), or a HbA1c≥ 7% at visit 12 (Week 24)
* Dosage of metformin compliant with the inclusion criteria of visit 1 (i.e. maximum tolerated dosage, with a minimum daily dosage of 1g), and maintained stable during the comparative period.
Exclusion criteria:
* Previous treatment with Glucagon Like Peptide-1 analogues or insulin in the past year (except in case of temporary treatment for gestational diabetes, surgery, hospitalization...),
* Treatment with thiazolidinediones or α-Glucosidases inhibitors within 3 months prior to study entry,
* Diabetes other than Type 2 diabetes (e.g. secondary to pancreatic disorders, drug or chemical agents intake),
* Pregnant women (women of childbearing potential must have a negative pregnancy test at study entry and a medically approved contraceptive method),
* Lactating women,
* Hospitalized patients (except hospitalization for routine diabetes check-up),
* Active proliferative retinopathy, as defined by a photocoagulation or vitrectomy occurrence in the 6 months prior to study entry, or any other unstable (rapidly progressing) retinopathy that may require photocoagulation or surgical treatment during the study, documented by a retina examination within 2 years prior to study entry,
* Impaired renal function (creatinine clearance \< 60 mL/mn),
* Impaired hepatic function (Alanine Aminotransferase, Aspartate Aminotransferase 2.5 times the upper limit of normal range),
* Personal or family history of medullary thyroid carcinoma,
* Multiple endocrine neoplasia syndrome type 2,
* Severe gastro-intestinal disease (including inflammatory bowel disease or diabetic gastroparesis),
* Congestive heart failure,
* History of acute pancreatitis,
* Treatment with corticosteroids with potential systemic action for more than 10 days within 3 months prior to study entry,
* Alcohol or drug abuse in the past 5 years,
* History of sensitivity to the study drugs or to drugs with a similar chemical structure.
* Night shift worker,
* Presence of any condition (medical, psychological, social or geographical), current or anticipated that would compromise the patients safety or limit the patient successful participation in the study,
* Participation in a clinical trial (drug or device) within 3 months prior to study entry,
* Refusal or inability to give informed consent to participate in the study,
* Patient is the Investigator or any sub-Investigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the protocol.
Additional exclusion criteria for the extension period:
* Treatment with oral antidiabetic drugs other than metformin and patient's usual sulfonylurea if any, or with insulin during the comparative period (except in case of an emergency, for a period of time less than 7 days),
* Treatment with corticosteroids with potential systemic action within the last 3 months of the comparative period.
* History of sensitivity to insulin glargine.
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