Phase 3
Completed N=680
GLP-1 Receptor Agonist Lixisenatide (Morning or Evening) in Patients With Type 2 Diabetes for Glycemic Control and Safety Evaluation, on Top of Metformin
Source: ClinicalTrials.gov NCT00712673 ↗Enrolled (actual)
680
Serious AEs
8.5%
Results posted
Dec 2016
Primary outcomePrimary: Absolute Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 24 — -0.38; -0.87; -0.75 percentage of hemoglobin — p=<0.0001
◆ Published Evidence
Highly cited
171citations · ~13 / year
Efficacy and safety of lixisenatide once-daily morning or evening injections in type 2 diabetes inadequately controlled on metformin (GetGoal-M).
Summary
The purpose of this study is to evaluate the benefits and risks of lixisenatide (AVE0010), in comparison to placebo, as an add-on treatment to metformin, over a period of 24 weeks of treatment, followed by an extension.
The primary objective is to assess the effects of lixisenatide as an add-on treatment to metformin in terms of glycosylated hemoglobin (HbA1c) reduction (absolute change) at Week 24.
The secondary objectives are to assess the effect of lixisenatide, in comparison to placebo, when administered in the evening within 1 hour prior to the meal in terms of HbA1c reduction, percentage of patients reaching HbA1c less than (<) 7 percent (%), percentage of patients reaching HbA1c less than or equal to 6.5%, fasting plasma glucose (FPG), plasma glucose, plasma insulin, C-peptide, glucagon, and proinsulin during a 2-hour standardized meal test (only in morning injection arms), body weight, beta-cell function assessed by homeostasis model assessment (HOMA)-beta, fasting plasma insulin (FPI) and adiponectin; to evaluate safety, tolerability, pharmacokinetics (PK) and anti-lixisenatide antibody development, beta-cell function 4 weeks after study drug discontinuation (only in patients from the morning injection arms in some selected centers).
Linked Publications (4)
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Efficacy and safety of lixisenatide once-daily morning or evening injections in type 2 diabetes inadequately controlled on metformin (GetGoal-M).
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Efficacy of lixisenatide in patients with type 2 diabetes: A post hoc analysis of patients with diverse β-cell function in the GetGoal-M and GetGoal-S trials.
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Glucagon-like peptide 1 (GLP-1) receptor agonists for people with chronic kidney disease and diabetes.
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Postprandial Glucagon Reductions Correlate to Reductions in Postprandial Glucose and Glycated Hemoglobin with Lixisenatide Treatment in Type 2 Diabetes Mellitus: A Post Hoc Analysis.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Absolute Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 24 |
-0.38; -0.87; -0.75 | <0.0001 sig |
| SECONDARY Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 |
-0.25; -1.19; -0.81 | — |
| SECONDARY Change From Baseline in 2-Hour Postprandial Plasma Glucose (PPG) at Week 24 |
-1.41; -5.92 | — |
| SECONDARY Change From Baseline in Body Weight at Week 24 |
-1.64; -2.01; -2.02 | — |
| SECONDARY Change From Baseline in Fasting Plasma Insulin (FPI) at Week 24 |
-6.23; -5.09; -1.88 | — |
| SECONDARY Change From Baseline in 2-Hour Postprandial Plasma Insulin (PPI) at Week 24 |
-25.67; -87.24 | — |
| SECONDARY Change From Baseline in Fasting Proinsulin at Week 24 |
-3.78; -7.78 | — |
| SECONDARY Change From Baseline in 2-Hour Postprandial Proinsulin at Week 24 |
-6.83; -18.88 | — |
| SECONDARY Change From Baseline in Fasting C-Peptide at Week 24 |
-0.13; -0.10 | — |
| SECONDARY Change From Baseline in 2-Hour Postprandial C-Peptide at Week 24 |
-0.20; -0.46 | — |
| SECONDARY Change From Baseline in Fasting Glucagon at Week 24 |
-13.53; -13.27 | — |
| SECONDARY Change From Baseline in 2-Hour Postprandial Glucagon at Week 24 |
-12.79; -27.04 | — |
| SECONDARY Change From Baseline in Adiponectin at Week 24 |
0.54; 0.55; 0.58 | — |
| SECONDARY Change From Baseline in Beta-cell Function Assessed by Homeostasis Model Assessment for Beta-cell Function (HOMA-beta) at Week 24 |
-4.16; 7.96; 4.80 | — |
| SECONDARY Percentage of Patients Requiring Rescue Therapy During the Main 24-Week Period |
10.6; 2.7; 3.9 | — |
| SECONDARY Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than 7% at Week 24 |
22.0; 43.0; 40.6 | — |
| SECONDARY Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than or Equal to 6.5% at Week 24 |
10.4; 23.8; 19.2 | — |
Eligibility Criteria
Inclusion Criteria
- Type 2 diabetes mellitus, diagnosed for at least 1 year before screening visit, insufficiently controlled with metformin at a stable dose of at least 1.5 gram/ day (g/day) for at least 3 months prior to screening visit
Exclusion Criteria
- HbA1c ) 10% at screening
- At the time of screening age 250 milligram per deciliter (mg/dL) (>13.9 millimole per liter [mmol/L])
- Body mass index (BMI) 5 kg during the 3 months preceding the study screening visit
- History of unexplained pancreatitis, chronic pancreatitis, pancreatectomy, stomach/gastric surgery, inflammatory bowel disease
- History of metabolic acidosis, including diabetic ketoacidosis, within 1 year prior to screening
- Hemoglobinopathy or hemolytic anemia, receipt of blood or plasma products within 3 months prior to the time of screening
- Within the last 6 months prior to screening, history of myocardial infarction, stroke, or heart failure requiring hospitalization
- Known history of drug or alcohol abuse within 6 months prior to the time of screening
- Cardiovascular, hepatic, neurological, endocrine disease, active malignant tumor or other major systemic disease or patients with short life expectancy making implementation of the protocol or interpretation of the study results difficult, history or presence of clinically significant diabetic retinopathy, history or presence of macular edema likely to require laser treatment within the study period
- Uncontrolled or inadequately controlled hypertension at the time of screening with a resting supine systolic blood pressure or diastolic blood pressure >180 millimeter of mercury (mmHg) or >95 mmHg, respectively
- Laboratory findings at the time of screening: aspartate aminotransferase, alanine aminotransferase, or alkaline phosphatase: >2 times upper limit of normal (ULN) laboratory range; amylase and/or lipase: >3 times ULN; total bilirubin: >1.5 times ULN (except in case of Gilbert's syndrome); Hemoglobin 1.4 mg/dL in women and creatinine >1.5 mg/dL in men
- Clinically relevant history of gastrointestinal disease associated with prolonged nausea and vomiting, including, but not limited to, gastroparesis and gastroesophageal reflux disease requiring medical treatment, within 6 months prior to the time of screening
- Allergic reaction to any glucagon-like peptide-1(GLP-1) agonist in the past (for example, exenatide, liraglutide) or to metacresol
- Additional exclusion criteria at the end of the run-in phase: informed consent withdrawal; lack of compliance during the single-blind placebo run-in phase (>2 injections missed); and patient with any adverse event which precludes the inclusion in the study, as assessed by the investigator
Data sourced from ClinicalTrials.gov (NCT00712673) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.