Efficacy and Safety of the Insulin Glargine/Lixisenatide Fixed Ratio Combination (FRC) Versus GLP-1 Receptor Agonist in Patients With Type 2 Diabetes, With a FRC Extension Period
- Conditions
- Type 2 Diabetes Mellitus
- Interventions
- Drug: Insulin glargine/lixisenatide fixed ratio combination
- Registration Number
- NCT02787551
- Lead Sponsor
- Sanofi
- Brief Summary
Primary Objective:
To demonstrate the superiority of the insulin glargine/lixisenatide fixed ratio combination (FRC) versus GLP-1 receptor agonist (GLP-1 RA) in hemoglobin A1c (HbA1c) change.
Secondary Objectives:
To compare the overall efficacy and safety of the insulin glargine/lixisenatide FRC to GLP-1 RA on top of metformin (with or without pioglitazone, with or without sodium-glucose co-transporter 2 \[SGLT2\] inhibitor) in participants with type 2 diabetes.
To evaluate safety, efficacy and other endpoints of FRC up to the end of the extension period.
- Detailed Description
The maximum duration for GLP1-RA participants was approximately 29 weeks: up to 2 week screening period, a 26 week treatment period (either randomized or uncontrolled), and a 3 or 9 day post-treatment safety follow-up period.
Maximum duration for FRC participants was approximately 55 weeks: up to 2-week screening period, a 26-week randomized treatment period, a 26-week extension period and a 3-day post-treatment safety follow-up period.
All primary and secondary efficacy, safety and other outcome measures were assessed at the end of the extension period.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 514
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description GLP-1 Receptor Agonist exenatide Core period: GLP-1 RA receptor agonist (liraglutide QD, exenatide twice daily \[BID\], exenatide extended-release QW, albiglutide QW, or dulaglutide QW) injected subcutaneously for 26 weeks on top of OAD therapy. GLP-1 RAs were administered as per local labeling at the same dose schedule as prior to randomization. GLP-1 Receptor Agonist albiglutide Core period: GLP-1 RA receptor agonist (liraglutide QD, exenatide twice daily \[BID\], exenatide extended-release QW, albiglutide QW, or dulaglutide QW) injected subcutaneously for 26 weeks on top of OAD therapy. GLP-1 RAs were administered as per local labeling at the same dose schedule as prior to randomization. GLP-1 Receptor Agonist liraglutide Core period: GLP-1 RA receptor agonist (liraglutide QD, exenatide twice daily \[BID\], exenatide extended-release QW, albiglutide QW, or dulaglutide QW) injected subcutaneously for 26 weeks on top of OAD therapy. GLP-1 RAs were administered as per local labeling at the same dose schedule as prior to randomization. GLP-1 Receptor Agonist exenatide extended-release Core period: GLP-1 RA receptor agonist (liraglutide QD, exenatide twice daily \[BID\], exenatide extended-release QW, albiglutide QW, or dulaglutide QW) injected subcutaneously for 26 weeks on top of OAD therapy. GLP-1 RAs were administered as per local labeling at the same dose schedule as prior to randomization. Insulin Glargine/Lixisenatide Fixed Ratio Combination (FRC) Insulin glargine/lixisenatide fixed ratio combination Core period: FRC injected subcutaneously once daily (QD) for 26 weeks on top of oral anti-diabetic drug (OAD) therapy. Dose individually adjusted. Single arm extension period: Participants who completed core treatment period and met eligibility criteria entered in extension treatment period and received same treatment (FRC injected subcutaneously QD on top of OAD therapy) for 26 weeks (up to Week 52). Dose individually adjusted. GLP-1 Receptor Agonist dulaglutide Core period: GLP-1 RA receptor agonist (liraglutide QD, exenatide twice daily \[BID\], exenatide extended-release QW, albiglutide QW, or dulaglutide QW) injected subcutaneously for 26 weeks on top of OAD therapy. GLP-1 RAs were administered as per local labeling at the same dose schedule as prior to randomization.
- Primary Outcome Measures
Name Time Method Change From Baseline in Glycated Hemoglobin (HbA1c) to Week 26: Core Period Baseline, Week 26 Change in HbA1c was calculated by subtracting baseline value from Week 26 value. Adjusted least squares (LS) mean and standard error (SE) were obtained from Mixed-effect model with repeated measures (MMRM) to account for missing data using all available post baseline data during the 26 week treatment period.
Change From Baseline in Glycated Hemoglobin (HbA1c) to Week 52: Single Arm Extension Period Baseline, Week 52 Change in HbA1c was calculated by subtracting baseline value from Week 52 value.
- Secondary Outcome Measures
Name Time Method Percentage of Participants Reaching HbA1c <7 % or <=6.5% at Week 52: Single Arm Extension Period Week 52 Participants without any available HbA1c assessment at Week 52 were considered as non-responders.
Change From Baseline in Fasting Plasma Glucose (FPG) to Week 26: Core Period Baseline, Week 26 Change in FPG was calculated by subtracting baseline value from Week 26 value. Adjusted LS means and SE were obtained from MMRM to account for missing data using all available post baseline data during the 26 week treatment period.
Change From Baseline in 2-Hour Blood Glucose Excursion During Standardized Meal Test to Week 52: Single Arm Extension Period Baseline, Week 52 2-hour plasma glucose excursion = 2-hour PPG value minus plasma glucose value obtained 30 minutes prior to the start of meal and before IMP administration if IMP was injected before breakfast. Change in plasma glucose excursions were calculated by subtracting baseline value from Week 52 value. Missing data was imputed using LOCF.
Percentage of Participants Requiring Rescue Therapy During the 26 Week Treatment Period: Core Period From Baseline to Week 26 Routine HbA1c value was used to determine the requirement of rescue medication. Threshold values at Week 12 or later on Week 12: HbA1c \>8%.
Change From Baseline in Body Weight at Week 26: Core Period Baseline, Week 26 Change in body weight was calculated by subtracting baseline value from Week 26 value.
Percentage of Participants Reaching HbA1c <7% or <=6.5% at Week 26: Core Period Week 26 Participants without any available HbA1c assessment at Week 26 were considered as non-responders.
Change From Baseline in the Daily Average of the 7-point Self-monitored Plasma Glucose (SMPG) to Week 26: Core Period Baseline, Week 26 The 7-point SMPG profile was measured at the following 7 points: pre-prandial and 2 hours postprandial for breakfast, lunch, dinner and at bedtime. Two hours postprandial (breakfast, lunch and dinner) was defined as 2 hours after the start of the meal. Adjusted LS means and SE were obtained from MMRM to account for missing data using all available post baseline data during the 26 week treatment period.
Change From Baseline in 2-Hour Postprandial Plasma Glucose (PPG) During Standardized Meal Test to Week 26: Core Period Baseline, Week 26 The 2-hour PPG test measured blood glucose 2 hours after eating a liquid standardized breakfast meal. Change in PPG was calculated by subtracting baseline value from Week 26 value. Missing data was imputed using last observation carried forward (LOCF).
Change From Baseline in 2-Hour Postprandial Plasma Glucose (PPG) During Standardized Meal Test to Week 52: Single Arm Extension Period Baseline, Week 52 The 2-hour PPG test measured blood glucose 2 hours after eating a liquid standardized breakfast meal. Change in PPG was calculated by subtracting baseline value from Week 52 value. Missing data was imputed using LOCF.
Change From Baseline in the Daily Average of the 7-point Self-monitored Plasma Glucose (SMPG) to Week 52: Single Arm Extension Period Baseline, Week 52 The 7-point SMPG profile was measured at the following 7 points: pre-prandial and 2 hours postprandial for breakfast, lunch, dinner and at bedtime. Two hours postprandial (breakfast, lunch and dinner) was defined as 2 hours after the start of the meal.
Percentage of Participants Requiring Rescue Therapy During the 52 Week Treatment Period: Single Arm Extension Period From Week 26 to Week 52 Routine HbA1c value was used to determine the requirement of rescue medication. Threshold values at Week 12 or later on Week 12: HbA1c \>8%.
Change From Baseline in 2-Hour Blood Glucose Excursion During Standardized Meal Test to Week 26: Core Period Baseline, Week 26 2-hour plasma glucose excursion = 2-hour PPG value minus plasma glucose value obtained 30 minutes prior to the start of meal and before investigational medicinal product (IMP) administration if IMP was injected before breakfast. Change in plasma glucose excursions were calculated by subtracting baseline value from Week 26 value. Missing data was imputed using LOCF.
Change From Baseline in Body Weight to Week 52: Single Arm Extension Period Baseline, Week 52 Change in body weight was calculated by subtracting baseline value from Week 52 value.
Number of Documented Symptomatic Hypoglycemia Events Per Participant-Year: Core Period From Baseline to Week 26 Documented symptomatic hypoglycemia was an event during which symptoms of hypoglycemia were accompanied by a measured plasma glucose concentration of \<=3.9 mmol/L (70 mg/dL). Hypoglycemic episodes with plasma glucose of \<3.0 mmol/L (54 mg/dL) were also analyzed.
Number of Documented Symptomatic Hypoglycemia Events Per Participant-Year: Single Arm Extension Period From Baseline to Week 52 Documented symptomatic hypoglycemia was an event during which symptoms of hypoglycemia were accompanied by a measured plasma glucose concentration of \<=3.9 mmol/L (70 mg/dL). Hypoglycemic episodes with plasma glucose of \<3.0 mmol/L (54 mg/dL) were also analyzed.
Change From Baseline in Fasting Plasma Glucose (FPG) to Week 52: Single Arm Extension Period Baseline, Week 52 Change in FPG was calculated by subtracting baseline value from Week 52 value.
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Trial Locations
- Locations (124)
Investigational Site Number 8400033
🇺🇸Baltimore, Maryland, United States
Investigational Site Number 8400079
🇺🇸Albany, New York, United States
Investigational Site Number 8400019
🇺🇸Columbus, Ohio, United States
Investigational Site Number 8400107
🇺🇸Sugar Land, Texas, United States
Investigational Site Number 8400103
🇺🇸Bakersfield, California, United States
Investigational Site Number 8400124
🇺🇸Lamont, California, United States
Investigational Site Number 8400137
🇺🇸Fresno, California, United States
Investigational Site Number 8400043
🇺🇸Huntington Park, California, United States
Investigational Site Number 8400027
🇺🇸Lancaster, California, United States
Investigational Site Number 8400098
🇺🇸Los Angeles, California, United States
Investigational Site Number 8400013
🇺🇸Los Angeles, California, United States
Investigational Site Number 8400042
🇺🇸Mission Hills, California, United States
Investigational Site Number 8400006
🇺🇸Northridge, California, United States
Investigational Site Number 8400021
🇺🇸Orange, California, United States
Investigational Site Number 8400126
🇺🇸Rialto, California, United States
Investigational Site Number 8400094
🇺🇸Santa Ana, California, United States
Investigational Site Number 8400009
🇺🇸Ventura, California, United States
Investigational Site Number 8400114
🇺🇸Jacksonville, Florida, United States
Investigational Site Number 8400058
🇺🇸Port Charlotte, Florida, United States
Investigational Site Number 8400045
🇺🇸Lawrenceville, Georgia, United States
Investigational Site Number 8400096
🇺🇸Snellville, Georgia, United States
Investigational Site Number 8400112
🇺🇸West Palm Beach, Florida, United States
Investigational Site Number 8400049
🇺🇸Avon, Indiana, United States
Investigational Site Number 8400023
🇺🇸Springfield, Illinois, United States
Investigational Site Number 8400053
🇺🇸Avon, Indiana, United States
Investigational Site Number 8400120
🇺🇸Avon, Indiana, United States
Investigational Site Number 8400085
🇺🇸Avon, Indiana, United States
Investigational Site Number 8400041
🇺🇸Evansville, Indiana, United States
Investigational Site Number 8400130
🇺🇸Council Bluffs, Iowa, United States
Investigational Site Number 8400034
🇺🇸Lexington, Kentucky, United States
Investigational Site Number 8400091
🇺🇸Lexington, Kentucky, United States
Investigational Site Number 8400088
🇺🇸New Orleans, Louisiana, United States
Investigational Site Number 8400051
🇺🇸Jefferson City, Missouri, United States
Investigational Site Number 8400044
🇺🇸Henderson, Nevada, United States
Investigational Site Number 8400083
🇺🇸Papillion, Nebraska, United States
Investigational Site Number 8400061
🇺🇸New York, New York, United States
Investigational Site Number 8400095
🇺🇸Staten Island, New York, United States
Investigational Site Number 8400067
🇺🇸West Seneca, New York, United States
Investigational Site Number 8400123
🇺🇸North Massapequa, New York, United States
Investigational Site Number 8400111
🇺🇸Yonkers, New York, United States
Investigational Site Number 8400020
🇺🇸Morehead City, North Carolina, United States
Investigational Site Number 8400065
🇺🇸Wilmington, North Carolina, United States
Investigational Site Number 8400018
🇺🇸Fargo, North Dakota, United States
Investigational Site Number 8400056
🇺🇸Dayton, Ohio, United States
Investigational Site Number 8400129
🇺🇸Scottdale, Pennsylvania, United States
Investigational Site Number 8400125
🇺🇸Mentor, Ohio, United States
Investigational Site Number 8400076
🇺🇸Smithfield, Pennsylvania, United States
Investigational Site Number 8400104
🇺🇸Warwick, Rhode Island, United States
Investigational Site Number 8400139
🇺🇸Austin, Texas, United States
Investigational Site Number 8400001
🇺🇸Dallas, Texas, United States
Investigational Site Number 8400118
🇺🇸Edinburg, Texas, United States
Investigational Site Number 8400135
🇺🇸Schertz, Texas, United States
Investigational Site Number 8400014
🇺🇸North Richland Hills, Texas, United States
Investigational Site Number 8400075
🇺🇸Shavano Park, Texas, United States
Investigational Site Number 8400054
🇺🇸Orem, Utah, United States
Investigational Site Number 1240003
🇨🇦Burlington, Canada
Investigational Site Number 8400092
🇺🇸Weber City, Virginia, United States
Investigational Site Number 1240006
🇨🇦Corunna, Canada
Investigational Site Number 2330002
🇪🇪Pärnu, Estonia
Investigational Site Number 1240001
🇨🇦Vancouver, Canada
Investigational Site Number 1240002
🇨🇦Red Deer, Canada
Investigational Site Number 2330003
🇪🇪Tallinn, Estonia
Investigational Site Number 2760001
🇩🇪Dresden, Germany
Investigational Site Number 2760003
🇩🇪Oldenburg In Holstein, Germany
Investigational Site Number 3760002
🇮🇱Haifa, Israel
Investigational Site Number 3800008
🇮🇹Bergamo, Italy
Investigational Site Number 3800001
🇮🇹Milano, Italy
Investigational Site Number 3800005
🇮🇹Napoli, Italy
Investigational Site Number 3800003
🇮🇹Roma, Italy
Investigational Site Number 6420003
🇷🇴Cluj Napoca, Romania
Investigational Site Number 6420002
🇷🇴Oradea, Romania
Investigational Site Number 7030006
🇸🇰Bratislava, Slovakia
Investigational Site Number 7030009
🇸🇰Lubochna, Slovakia
Investigational Site Number 7030005
🇸🇰Malacky, Slovakia
Investigational Site Number 7030003
🇸🇰Zilina, Slovakia
Investigational Site Number 7240012
🇪🇸Alzira, Spain
Investigational Site Number 7240005
🇪🇸Barcelona, Spain
Investigational Site Number 7240002
🇪🇸Ferrol, Spain
Investigational Site Number 7240011
🇪🇸Pozuelo De Alarcón, Spain
Investigational Site Number 7240008
🇪🇸Málaga, Spain
Investigational Site Number 7240003
🇪🇸Quart De Poblet, Spain
Investigational Site Number 7240004
🇪🇸Sevilla, Spain
Investigational Site Number 7240006
🇪🇸Sabadell, Spain
Investigational Site Number 7240007
🇪🇸Sevilla, Spain
Investigational Site Number 7240009
🇪🇸sEVILLA, Spain
Investigational Site Number 8400008
🇺🇸Houston, Texas, United States
Investigational Site Number 8400109
🇺🇸Houston, Texas, United States
Investigational Site Number 8400063
🇺🇸Houston, Texas, United States
Investigational Site Number 8400106
🇺🇸Houston, Texas, United States
Investigational Site Number 8400047
🇺🇸Phoenix, Arizona, United States
Investigational Site Number 8400133
🇺🇸Miami, Florida, United States
Investigational Site Number 8400038
🇺🇸Indianapolis, Indiana, United States
Investigational Site Number 8400089
🇺🇸San Antonio, Texas, United States
Investigational Site Number 8400025
🇺🇸Salt Lake City, Utah, United States
Investigational Site Number 8400064
🇺🇸Birmingham, Alabama, United States
Investigational Site Number 8400099
🇺🇸Oklahoma City, Oklahoma, United States
Investigational Site Number 3800004
🇮🇹Roma, Italy
Investigational Site Number 3800002
🇮🇹Bologna, Italy
Investigational Site Number 3800006
🇮🇹Milano, Italy
Investigational Site Number 8400071
🇺🇸Denver, Colorado, United States
Investigational Site Number 8400036
🇺🇸Denver, Colorado, United States
Investigational Site Number 2330001
🇪🇪Tallinn, Estonia
Investigational Site Number 6420001
🇷🇴Bucuresti, Romania
Investigational Site Number 2330004
🇪🇪Viljandi, Estonia
Investigational Site Number 8400090
🇺🇸Columbia, South Carolina, United States
Investigational Site Number 3760004
🇮🇱Tel Aviv, Israel
Investigational Site Number 6420006
🇷🇴Brasov, Romania
Investigational Site Number 6420008
🇷🇴Buzau, Romania
Investigational Site Number 6420007
🇷🇴Târgu-Mureş, Romania
Investigational Site Number 7030002
🇸🇰Lucenec, Slovakia
Investigational Site Number 8400078
🇺🇸Marrero, Louisiana, United States
Investigational Site Number 7030001
🇸🇰Roznava, Slovakia
Investigational Site Number 8400073
🇺🇸Fountain Hills, Arizona, United States
Investigational Site Number 3760006
🇮🇱Jerusalem, Israel
Investigational Site Number 6420009
🇷🇴Targoviste, Romania
Investigational Site Number 6420005
🇷🇴Timisoara, Romania
Investigational Site Number 7030007
🇸🇰Presov, Slovakia
Investigational Site Number 7030004
🇸🇰Trencin, Slovakia
Investigational Site Number 8400032
🇺🇸Metairie, Louisiana, United States
Investigational Site Number 3760001
🇮🇱Haifa, Israel
Investigational Site Number 3760005
🇮🇱Jerusalem, Israel
Investigational Site Number 6420004
🇷🇴Bacau, Romania
Investigational Site Number 7030008
🇸🇰Sabinov, Slovakia
Investigational Site Number 8400084
🇺🇸Tampa, Florida, United States