Phase 3
Completed N=859
GLP-1 Receptor Agonist Lixisenatide in Patients With Type 2 Diabetes for Glycemic Control and Safety Evaluation, on Top of Sulfonylurea
Source: ClinicalTrials.gov NCT00713830 ↗Enrolled (actual)
859
Serious AEs
10.8%
Results posted
Dec 2016
Primary outcomePrimary: Absolute Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 24 — -0.10; -0.85 percentage of hemoglobin — p=<0.0001
◆ Published Evidence
Highly cited
126citations · ~11 / year
Beneficial effects of once-daily lixisenatide on overall and postprandial glycemic levels without significant excess of hypoglycemia in type 2 diabetes inadequately controlled on a sulfonylurea with or without metformin (GetGoal-S).
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 sulfonylurea without or with metformin, over a period of 24 weeks of treatment, followed by an extension.
The primary objective is to assess the effects of lixisenatide when added to sulfonylurea with or without metformin on glycemic control in terms of glycosylated hemoglobin (HbA1c) reduction (absolute change) at Week 24.
The secondary objectives are to assess the effects of lixisenatide on percentage of patients reaching HbA1c less than (<) 7 percent (%); percentage of patients reaching HbA1c less than or equal to (<=) 6.5%; body weight; fasting plasma glucose (FPG); beta-cell function assessed by homeostasis model assessment (HOMA) beta; 2-hour postprandial plasma glucose (PPG), glucagon, insulin, proinsulin, and C-peptide after a standardized meal challenge test in a sub-study in all patients in selected centers; to evaluate safety, tolerability, pharmacokinetics (PK) and anti-lixisenatide antibody development.
Linked Publications (4)
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Beneficial effects of once-daily lixisenatide on overall and postprandial glycemic levels without significant excess of hypoglycemia in type 2 diabetes inadequately controlled on a sulfonylurea with or without metformin (GetGoal-S).
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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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Lixisenatide improves glycemic outcomes of Japanese patients with type 2 diabetes: a meta-analysis.
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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 |
-0.10; -0.85 | <0.0001 sig |
| SECONDARY Change From Baseline in 2-Hour Postprandial Plasma Glucose (PPG) at Week 24 |
-0.21; -6.19 | — |
| SECONDARY Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 |
-0.36; -0.99 | — |
| SECONDARY Change From Baseline in Body Weight at Week 24 |
-0.93; -1.76 | — |
| SECONDARY Change From Baseline in Beta-cell Function Assessed by HOMA-beta at Week 24 |
6.63; 4.83 | — |
| SECONDARY Change From Baseline in Fasting Glucagon and 2-hour Postprandial Glucagon at Week 24 |
2.03; -2.10; -1.19; -23.33 | — |
| SECONDARY Change From Baseline in Fasting Plasma Insulin (FPI) and 2-hour Postprandial Plasma Insulin at Week 24 |
1.42; -4.03; -2.22; -67.67 | — |
| SECONDARY Change From Baseline in Fasting Proinsulin and 2-hour Postprandial Proinsulin at Week 24 |
-1.05; -6.33; 3.55; -4.20 | — |
| SECONDARY Change From Baseline in Fasting C-peptide and 2-hour Postprandial C-peptide at Week 24 |
-0.06; -0.07; -0.14; -0.37 | — |
| SECONDARY Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than 7% at Week 24 |
13.5; 36.4 | — |
| SECONDARY Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than or Equal to 6.5% at Week 24 |
4.7; 19.3 | — |
| SECONDARY Percentage of Patients Requiring Rescue Therapy During Main 24-Week Period |
12.6; 4.0 | — |
Eligibility Criteria
Inclusion Criteria
- Type 2 diabetes mellitus, diagnosed for at least 1 year before screening visit, insufficiently controlled with a sulfonylurea alone or a sulfonylurea in association with metformin
Exclusion Criteria
- HbA1c less than ( ) 10% at screening
- At the time of screening age less than legal age of majority
- Pregnant or breastfeeding women or women of childbearing potential with no effective contraceptive method
- Type 1 diabetes mellitus
- Sulfonylurea less than the maximum effective dose according to local labeling
- Sulfonylurea not at a stable (unchanged) dose for at least 3 months prior to screening
- In case of treatment with metformin in association with sulfonylurea, no stable (unchanged) treatment with metformin of at least 1.5 gram per day (except at least 0.75 gram per day in Japan and at least 1.0 gram per day in South Korea), for at least 3 months prior to screening visit
- FPG at screening >250 milligram per deciliter (mg/dL) (>13.9 millimole per liter [mmol/L])
- History of hypoglycemia unawareness
- Body mass index less than or equal to ( 5 kg during the 3 months preceding the 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 systolic blood pressure (SBP) or diastolic blood pressure (DBP) >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 the 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 serum creatinine >1.5 mg/dL in men (applicable only for patients with metformin treatment)
- End-stage renal disease as defined by a serum creatinine clearance of 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 (NCT00713830) 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.