Efficacy Assessment of Insulin Glargine Versus LiraglutidE After Oral Agents Failure
- Conditions
- Diabetes Mellitus, Type 2
- Interventions
- Registration Number
- NCT01117350
- Lead Sponsor
- Sanofi
- Brief Summary
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
- Detailed Description
Maximum estimated study duration per patient: either 27 weeks (patients randomized to insulin glargine arm) or 51 weeks (patients randomized to liraglutide arm) broken down as follow:
* A 2-week of screening period,
* A 24-week comparative period,
* A 24-week extension period (only for patients treated with liraglutide, not adequately controlled at the end of the comparative period),
* A 1-week follow-up period
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 978
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Liraglutide 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. Insulin Glargine 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. Insulin Glargine Metformin 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. Liraglutide Metformin 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 Outcome Measures
Name Time Method Percentage of Patients Whose Glycosylated Haemoglobin (HbA1c) <7% at the End of the Comparative Period week 12, week 24 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 Outcome Measures
Name Time Method Daily Dose of Insulin Glargine week 1, week 2, week 6, week 12, week 24 Percentage of Patients Whose Glycosylated Haemoglobin (HbA1c) Has Decreased But Remains ≥7% at the End of the Comparative Period baseline (week -2), week 12, week 24 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 baseline (week -2), week 12, week 24 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 baseline (week -2), week 12, week 24 Change in HbA1C from baseline to the last observation carried forward (LOCF) measured during the comparative period = LOCF value - baseline value
Percentage of Patients Whose Glycosylated Haemoglobin (HbA1c) <7% at the End of the Extension Period week 36, week 48 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 Beginning to the End of the Extension Period week 24, week 30, week 36, week 48 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 valueGlycosylated Haemoglobin (HbA1c): Change From Beginning to the End of the Extension Period week 24, week 36, week 48 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
Self-Monitored Fasting Plasma Glucose (SMFPG) Measurements: Change From Baseline to the End of the Comparative Period baseline (week 0), week 6, week 12, week 18, week 24 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 valueSelf-Monitored 7-point Plasma Glucose (PG) Profile: Change From Baseline to the End of the Comparative Period baseline (week 0), week 12, week 24 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 valueSelf-Monitored 7-point Plasma Glucose (PG) Profile: Change From Beginning to the End of the Extension Period week 24, week 36, week 48 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 valueBody Weight: Change From Baseline to the End of the Comparative Period baseline (week 0), week 2, week 6, week 12, week 18, week 24 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 week 24, week 30, week 36, week 48 Change = Last weight value measured during the extension period (LOCF value) - weight value at beginning of the Extension Period (Week 24)
Daily Dose of Liraglutide week 1, week 2, week 6, week 12, week 24 Daily Dose of Insulin Glargine Administered During the Extension Period 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 all across the comparative period (from week 0 to week 24) 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 all across the extension period (from week 24 to week 48) 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.
Trial Locations
- Locations (136)
Investigational Site Number 840026
🇺🇸Longmont, Colorado, United States
Investigational Site Number 840007
🇺🇸Dallas, Texas, United States
Investigational Site Number 840020
🇺🇸Uniontown, Pennsylvania, United States
Investigational Site Number 076-001
🇧🇷Fortaleza, Brazil
Investigational Site Number 076-006
🇧🇷Fortaleza, Brazil
Investigational Site Number 840043
🇺🇸Tustin, California, United States
Investigational Site Number 840044
🇺🇸St. Louis, Missouri, United States
Investigational Site Number 840042
🇺🇸San Diego, California, United States
Investigational Site Number 840010
🇺🇸Rockville, Maryland, United States
Investigational Site Number 840039
🇺🇸San Diego, California, United States
Investigational Site Number 840002
🇺🇸Goodyear, Arizona, United States
Investigational Site Number 840037
🇺🇸Loma Linda, California, United States
Investigational Site Number 840047
🇺🇸Phoenix, Arizona, United States
Investigational Site Number 840023
🇺🇸Birmingham, Alabama, United States
Investigational Site Number 376004
🇮🇱Hadera, Israel
Investigational Site Number 376003
🇮🇱Tel-Aviv, Israel
Investigational Site Number 484001
🇲🇽Mexico, Mexico
Investigational Site Number 246004
🇫🇮Turku, Finland
Investigational Site Number 300003
🇬🇷Athens, Greece
Investigational Site Number 372001
🇮🇪Dublin 4, Ireland
Investigational Site Number 484003
🇲🇽Zapopan, Mexico
Investigational Site Number 250-011
🇫🇷Brest, France
Investigational Site Number 250-020
🇫🇷Strasbourg, France
Investigational Site Number 300004
🇬🇷Athens, Greece
Investigational Site Number 484004
🇲🇽Guadalajara, Mexico
Investigational Site Number 484002
🇲🇽Mexico, Mexico
Investigational Site Number 250022
🇫🇷Strasbourg, France
Investigational Site Number 724006
🇪🇸Cádiz, Spain
Investigational Site Number 724008
🇪🇸Madrid, Spain
Investigational Site Number 300001
🇬🇷Haidari, Athens, Greece
Investigational Site Number 528005
🇳🇱Woerden, Netherlands
Investigational Site Number 752-005
🇸🇪Karlskoga, Sweden
Investigational Site Number 250-017
🇫🇷Bois Guillaume Cedex, France
Investigational Site Number 643001
🇷🇺Moscow, Russian Federation
Investigational Site Number 724004
🇪🇸Valencia, Spain
Investigational Site Number 376002
🇮🇱Petah Tiqwa, Israel
Investigational Site Number 528002
🇳🇱Hoogeveen, Netherlands
Investigational Site Number 528007
🇳🇱Nijverdal, Netherlands
Investigational Site Number 643008
🇷🇺Kirov, Russian Federation
Investigational Site Number 250-021
🇫🇷Nanterre, France
Investigational Site Number 724001
🇪🇸Las Palmas de Gran Canaria, Spain
Investigational Site Number 724005
🇪🇸LLeida, Spain
Investigational Site Number 792-001
🇹🇷Antalya, Turkey
Investigational Site Number 752-002
🇸🇪Göteborg, Sweden
Investigational Site Number 703003
🇸🇰Zilina, Slovakia
Investigational Site Number 792-002
🇹🇷Istanbul, Turkey
Investigational Site Number 724007
🇪🇸Bilbao, Spain
Investigational Site Number 752-006
🇸🇪Motala, Sweden
Investigational Site Number 840034
🇺🇸Grand Junction, Colorado, United States
Investigational Site Number 840031
🇺🇸Kansas City, Kansas, United States
Investigational Site Number 840028
🇺🇸Denver, Colorado, United States
Investigational Site Number 840049
🇺🇸Fargo, North Dakota, United States
Investigational Site Number 528004
🇳🇱s-Hertogenbosch, Netherlands
Investigational Site Number 643005
🇷🇺Saratov, Russian Federation
Investigational Site Number 703004
🇸🇰Kosice, Slovakia
Investigational Site Number 250-002
🇫🇷Toulouse, France
Investigational Site Number 250-016
🇫🇷Venissieux, France
Investigational Site Number 752-03
🇸🇪Ängelholm, Sweden
Investigational Site Number 076-005
🇧🇷Marília, Brazil
Investigational Site Number 724003
🇪🇸Málaga, Spain
Investigational Site Number 724009
🇪🇸Sabadell, Spain
Investigational Site Number 840017
🇺🇸La Jolla, California, United States
Investigational Site Number 840036
🇺🇸La Mesa, California, United States
Investigational Site Number 840033
🇺🇸Mission Viejo, California, United States
Investigational Site Number 840045
🇺🇸Long Beach, California, United States
Investigational Site Number 840048
🇺🇸Mission Hills, California, United States
Investigational Site Number 840019
🇺🇸Palm Springs, California, United States
Investigational Site Number 840022
🇺🇸Lawrenceville, Georgia, United States
Investigational Site Number 840009
🇺🇸Arlington Heights, Illinois, United States
Investigational Site Number 840029
🇺🇸Roswell, Georgia, United States
Investigational Site Number 840050
🇺🇸Indianapolis, Indiana, United States
Investigational Site Number 840051
🇺🇸Springfield, Illinois, United States
Investigational Site Number 840004
🇺🇸Paducah, Kentucky, United States
Investigational Site Number 840038
🇺🇸Eagan, Minnesota, United States
Investigational Site Number 840030
🇺🇸Minneapolis, Minnesota, United States
Investigational Site Number 840012
🇺🇸St Louis, Missouri, United States
Investigational Site Number 840008
🇺🇸Blackwood, New Jersey, United States
Investigational Site Number 840027
🇺🇸Mineola, New York, United States
Investigational Site Number 840005
🇺🇸Hickory, North Carolina, United States
Investigational Site Number 840011
🇺🇸Staten Island, New York, United States
Investigational Site Number 840052
🇺🇸Winston-Salem, North Carolina, United States
Investigational Site Number 840006
🇺🇸Bryan, Ohio, United States
Investigational Site Number 840035
🇺🇸Cincinnati, Ohio, United States
Investigational Site Number 840016
🇺🇸Carnegie, Pennsylvania, United States
Investigational Site Number 840024
🇺🇸Rapid City, South Dakota, United States
Investigational Site Number 840013
🇺🇸Houston, Texas, United States
Investigational Site Number 840001
🇺🇸Dallas, Texas, United States
Investigational Site Number 840014
🇺🇸Renton, Washington, United States
Investigational Site Number 840046
🇺🇸Spokane, Washington, United States
Investigational Site Number 040-003
🇦🇹Stockerau, Austria
Investigational Site Number 040-004
🇦🇹Vienna, Austria
Investigational Site Number 076-007
🇧🇷Fortaleza, Brazil
Investigational Site Number 076-004
🇧🇷Belém, Brazil
Investigational Site Number 076-002
🇧🇷São Paulo, Brazil
Investigational Site Number 124-003
🇨🇦Mississauga, Canada
Investigational Site Number 124-001
🇨🇦Montreal, Canada
Investigational Site Number 124-008
🇨🇦Vancouver, Canada
Investigational Site Number 124-006
🇨🇦Montreal, Canada
Investigational Site Number 124-004
🇨🇦Toronto, Canada
Investigational Site Number 124-007
🇨🇦Victoria, Canada
Investigational Site Number 203001
🇨🇿Hradec Kralove, Czech Republic
Investigational Site Number 203003
🇨🇿Krnov, Czech Republic
Investigational Site Number 203006
🇨🇿Praha 5, Czech Republic
Investigational Site Number 246003
🇫🇮Harjavalta, Finland
Investigational Site Number 246001
🇫🇮Kuopio, Finland
Investigational Site Number 250-007
🇫🇷Annecy, France
Investigational Site Number 250-008
🇫🇷Cahors Cedex 9, France
Investigational Site Number 246002
🇫🇮Oulu, Finland
Investigational Site Number 250-003
🇫🇷Boulogne Billancourt, France
Investigational Site Number 250-009
🇫🇷La Rochelle Cedex 1, France
Investigational Site Number 250-004
🇫🇷Le Creusot, France
Investigational Site Number 250-012
🇫🇷Corbeil Essonnes, France
Investigational Site Number 250-006
🇫🇷Mantes La Jolie, France
Investigational Site Number 528001
🇳🇱Beek, Netherlands
Investigational Site Number 643-009
🇷🇺Kazan, Russian Federation
Investigational Site Number 643003
🇷🇺St-Ptetersburg, Russian Federation
Investigational Site Number 703001
🇸🇰Nitra, Slovakia
Investigational Site Number 703005
🇸🇰Nove Mesto nad Vahom, Slovakia
Investigational Site Number 752-001
🇸🇪Stockholm, Sweden
Investigational Site Number 752-007
🇸🇪Örebro, Sweden
Investigational Site Number 721002
🇪🇸Valencia, Spain
Investigational Site Number 724010
🇪🇸Vigo, Spain
Investigational Site Number 040-006
🇦🇹Salzburg, Austria
Investigational Site Number 040-007
🇦🇹Salzburg, Austria
Investigational Site Number 040-001
🇦🇹Vienna, Austria
Investigational Site Number 528003
🇳🇱Rotterdam, Netherlands
Investigational Site Number 643004
🇷🇺St-Petersburg, Russian Federation
Investigational Site Number 840015
🇺🇸Atco, New Jersey, United States
Investigational Site Number 643007
🇷🇺Samara, Russian Federation
Investigational Site Number 203005
🇨🇿Kromeriz, Czech Republic
Investigational Site Number 643006
🇷🇺Samara, Russian Federation
Investigational Site Number 703002
🇸🇰Bratislava, Slovakia
Investigational Site Number 040-005
🇦🇹Vienna, Austria
Investigational Site Number 040-002
🇦🇹Vienna, Austria
Investigational Site Number 203002
🇨🇿Olomouc, Czech Republic
Investigational Site Number 528006
🇳🇱Enschede, Netherlands