Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than 7% and at Least 5% Weight Loss From Baseline at Week 24
| Group | Value (percentage of participants) |
|---|---|
| Lixisenatide | 12.0 |
| Sitagliptin | 7.5 |
Trial · Interventional
CompletedPhase 3Results postedRegistry dataUnited States, Australia, Brazil, Canada, Chile, Germany, Guatemala, Mexico, Peru, Poland, Romania, Russia, Ukraine
1 trial · 1 completed · 1 with posted results
24-week Study Comparing Lixisenatide to Sitagliptin as add-on to Metformin in Obese Type 2 Diabetic Patients Younger Than 50 Years
NCT00976937Aug 2009 to Mar 2011
Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.
The purpose of this study is to evaluate benefits and risks of lixisenatide (AVE0010), in comparison to sitagliptin, as an add-on treatment to metformin, in obese (body mass index \[BMI\] greater than or equal to 30 kilogram per square meter \[kg/m\^2\]) type 2 diabetic patients less than 50 years of age, over a period of 24 weeks of treatment. The primary objective of this study is to assess the efficacy of lixisenatide, in comparison to sitagliptin, as an add-on treatment to metformin on a composite endpoint of glycemic control in terms of glycosylated hemoglobin (HbA1c) and body weight, at Week 24. Secondary objectives are to assess the effects of lixisenatide, in comparison to sitagliptin, as an add-on treatment to metformin on absolute changes in HbA1c values and body weight; fasting plasma glucose (FPG); plasma glucose, insulin, C-peptide, glucagon, and proinsulin during a 2-hour standardized meal test; insulin resistance assessed by homeostatic model assessment of insulin resistance (HOMA-IR); beta cell function assessed by homeostatic model assessment of beta-cell function (HOMA-beta); to evaluate safety, tolerability, and anti-lixisenatide antibody development.
Experimental
Lixisenatide
2-step initiation regimen of lixisenatide along with sitagliptin placebo: lixisenatide 10 microgram (mcg) once daily (QD) for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to Week 24 along with placebo matching to sitagliptin 100 milligram (mg) capsule orally QD up to Week 24.
Active comparator
Sitagliptin
Sitagliptin along with 2-step initiation regimen of volume matching lixisenatide placebo: sitagliptin 100 mg capsule orally QD up to Week 24 along with volume matching lixisenatide placebo 10 mcg QD for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to Week 24.
Outcomes the sponsor listed as primary.
Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than 7% and at Least 5% Weight Loss From Baseline at Week 24
Time frame · Week 24
Percentage of patients who met both criteria (HbA1c \<7% at Week 24 and at least 5% weight loss from baseline at Week 24) is reported. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to 3 days after the last dose of study drug or up to the introduction of rescue therapy, whichever is the earliest.
Absolute Change From Baseline in HbA1c at Week 24
Time frame · Baseline, Week 24
Absolute change = HbA1c value at Week 24 minus HbA1c value at baseline. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to 3 days after the last dose of study drug or up to the introduction of rescue therapy, whichever is the earliest.
Change From Baseline in Body Weight at Week 24
Time frame · Baseline, Week 24
Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to 3 days after the last dose of study drug or up to the introduction of rescue therapy, whichever is the earliest.
Change From Baseline in 2-hour Postprandial Plasma Glucose (PPG) at Week 24
Time frame · Baseline, Week 24
The 2-hour PPG test measured blood glucose 2 hours after eating a standardized meal. Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to the last dosing day of the study drug or up to the introduction of rescue therapy, whichever is the earliest.
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24
Time frame · Baseline, Week 24
Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to 1 day after the last dose of study drug or up to the introduction of rescue therapy, whichever is the earliest.
Change From Baseline in Glucose Excursion at Week 24
Time frame · Baseline, Week 24
Glucose excursion = 2-hour PPG minus plasma glucose 30 minutes prior to the standardized meal test, before study drug administration. Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to the last dosing day of the study drug or up to the introduction of rescue therapy, whichever is the earliest.
Change From Baseline in Fasting Plasma Insulin (FPI) and 2-hour Postprandial Plasma Insulin (PPI) at Week 24
Time frame · Baseline, Week 24
Change was calculated for fasting plasma insulin and 2-hour post prandial plasma insulin by subtracting the baseline value from Week 24 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to the last dosing day of the study drug or up to the introduction of rescue therapy, whichever is the earliest.
Change From Baseline in Fasting C-peptide and 2-hour Postprandial C-peptide at Week 24
Time frame · Baseline, Week 24
Change was calculated for fasting C-peptide and 2-hour postprandial C-peptide by subtracting the baseline value from Week 24 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to the last dosing day of study drug or up to the introduction of rescue therapy, whichever is the earliest.
Change From Baseline in Fasting Glucagon and 2-hour Postprandial Glucagon at Week 24
Time frame · Baseline, Week 24
Change was calculated for fasting glucagon and 2-hour postprandial glucagon by subtracting the baseline value from Week 24 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to the last dosing day of study drug or up to the introduction of rescue therapy, whichever is the earliest.
Change From Baseline in Fasting Proinsulin and 2-hour Postprandial Proinsulin at Week 24
Time frame · Baseline, Week 24
Change was calculated for fasting proinsulin and 2-hour postprandial proinsulin by subtracting the baseline value from Week 24 value. The on-treatment period for this efficacy variable is the time from the first dose of the study drug up to the last dosing day of study drug or up to the introduction of rescue therapy, whichever is the earliest.
Change From Baseline in Insulin Resistance Assessed by Homeostasis Model Assessment- Insulin Resistance (HOMA-IR) at Week 24
Time frame · Baseline, Week 24
HOMA-IR was derived from FPG and FPI as: (FPI \[micro units per milliliter\]\*FPG \[mmol/L\]) divided by 22.5. Change was calculated for HOMA-IR by subtracting the baseline value from Week 24 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to the last dosing day of study drug or up to the introduction of rescue therapy, whichever is the earliest.
Change From Baseline in Beta Cell Function Assessed by Homeostasis Model Assessment-Beta (HOMA-beta) at Week 24
Time frame · Baseline, Week 24
HOMA-beta was derived from FPG and FPI as: (20\*FPI \[micro units/milliliter\]) divided by (FPG \[mmol/L\] minus 3.5). Change was calculated for HOMA-beta by subtracting the baseline value from Week 24 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to the last dosing day of study drug or up to the introduction of rescue therapy, whichever is the earliest.
Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than or Equal to 6.5% at Week 24
Time frame · Week 24
The on-treatment period for this efficacy variable is the time from the first dose of study drug up to 3 days after the last dose of study drug or up to the introduction of rescue therapy, whichever is the earliest.
Percentage of Patients Requiring Rescue Therapy During 24-Week Period
Time frame · Baseline up to Week 24
Routine fasting self-measured plasma glucose (SMPG) and central laboratory FPG (and HbA1c after week 12) values were used to determine the requirement of rescue medication. If fasting SMPG value exceeded the specified limit for 3 consecutive days, the central laboratory FPG (and HbA1c after week 12) were performed. Threshold values - from baseline to Week 8: fasting SMPG/FPG \>270 milligram/deciliter (mg/dL) (15.0 mmol/L), from Week 8 to Week 12: fasting SMPG/FPG \>240 mg/dL (13.3 mmol/L), and from Week 12 to Week 24: fasting SMPG/FPG \>200 mg/dL (11.1 mmol/L) or HbA1c \>8.5%.
Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.
| Group | Value (percentage of participants) |
|---|---|
| Lixisenatide | 12.0 |
| Sitagliptin | 7.5 |
| Group | Value (percentage of hemoglobin) | Spread |
|---|---|---|
| Lixisenatide | -0.66 | 0.094 |
| Sitagliptin | -0.72 | 0.097 |
| Group | Value (kilogram) | Spread |
|---|---|---|
| Lixisenatide | -2.51 | 0.294 |
| Sitagliptin | -1.17 | 0.304 |
| Group | Value (mmol/L) | Spread |
|---|---|---|
| Lixisenatide | -3.35 | 0.377 |
| Sitagliptin | -1.44 | 0.384 |
| Group | Value (mmol/L) | Spread |
|---|---|---|
| Lixisenatide | -0.45 | 0.193 |
| Sitagliptin | -0.69 | 0.198 |
| Group | Value (mmol/L) | Spread |
|---|---|---|
| Lixisenatide | -2.55 | 0.272 |
| Sitagliptin | -0.42 | 0.275 |
| Group | Value (pmol/L) | Spread |
|---|---|---|
| Lixisenatide | -1.70 | 6.789 |
| Sitagliptin | -0.88 | 7.020 |
| Group | Value (nmol/L) | Spread |
|---|---|---|
| Lixisenatide | -0.02 | 0.039 |
| Sitagliptin | -0.02 | 0.038 |
| Group | Deaths | Serious events | Other events |
|---|---|---|---|
| Lixisenatide2-step initiation regimen of lixisenatide along with sitagliptin placebo. | – | 3 / 158 | 54 / 158 |
| SitagliptinSitagliptin along with 2-step initiation regimen of volume matching lixisenatide placebo. | – | 3 / 161 | 45 / 161 |
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