Phase 2
Completed N=142
Pharmacodynamic Effects of Lixisenatide Compared to Liraglutide in Patients With Type 2 Diabetes Not Adequately Controlled With Insulin Glargine With or Without Metformin
Source: ClinicalTrials.gov NCT01596504 ↗Enrolled (actual)
142
Serious AEs
1.4%
Results posted
Oct 2016
Primary outcomePrimary: Change From Baseline to Day 56 in Plasma Glucose Corrected Area Under The Plasma Concentration-Time Curve (AUC) From Time 0.5 Hours to 4.5 Hours — -13.33; -7.32; -8.72 h*mmol/L — p=<0.0001
Summary
Primary Objective:
- To investigate the effects of repeated subcutaneous doses of lixisenatide 20 μg once daily (QD) as compared to liraglutide 1.2 mg QD or 1.8 mg QD in reducing post-prandial plasma glucose (PPG) assessed as area under the plasma glucose-concentration-time curve (AUC) after a standardized breakfast at the end of a 8-week treatment period in participants with type 2 diabetes mellitus (T2DM) not adequately controlled with insulin glargine (± metformin).
Secondary Objectives:
* To assess the effects of lixisenatide 20 μg QD as compared to liraglutide 1.2 QD or 1.8 mg QD after an 8-week treatment period in participants with T2DM not adequately controlled with insulin glargine (± metformin) on:
* Post-prandial C-peptide, glucagon and appetite perceptions after a standardized breakfast,
* Appetite perceptions after standardized dinner,
* Gastric emptying after a standardized labelled test meal,
* Fasting plasma glucose, 24-hour plasma glucose profile,
* Glycosylated hemoglobin (HbA1c),
* Insulin glargine dose,
* 7-point self monitored plasma glucose (SMPG),
* Body weight and waist circumference,
* 24-hour heart rate and blood pressure,
* To assess lixisenatide and liraglutide safety and tolerability as add on treatment to insulin glargine (± metformin).
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline to Day 56 in Plasma Glucose Corrected Area Under The Plasma Concentration-Time Curve (AUC) From Time 0.5 Hours to 4.5 Hours |
-13.33; -7.32; -8.72 | <0.0001 sig |
| SECONDARY Change From Baseline to Day 56 in Plasma Glucose Corrected AUC From Time 0.5 Hours to 5.5 Hours |
-13.82; -9.09; -10.33 | — |
| SECONDARY Number of Participants With 2-Hour Post-prandial Plasma Glucose (PPG) <7.77 (mmol/L) at Day 56 |
35; 13; 11 | — |
| SECONDARY Change From Baseline to Day 56 in PPG Excursion |
-3.26; -1.79; -2.5 | — |
| SECONDARY Change From Baseline to Day 56 in Fasting Plasma Glucose (FPG) |
0.1; 0.12; 0.13 | — |
| SECONDARY Change From Baseline to Day 56 in Average 7-Point Self-Monitored Plasma Glucose (SMPG) |
-0.69; -0.76; -1.2 | — |
| SECONDARY Change From Baseline to Day 56 in Corrected C-Peptide AUC From Time 0.5 Hours to 5.5 Hours |
-1.16; 1.23; 0.88 | — |
| SECONDARY Change From Baseline to Day 56 in Corrected Glucagon AUC From Time 0.5 Hours to 5.5 Hours |
-16.56; 11.58; 5.6 | — |
| SECONDARY Change From Baseline to Day 56 in HbA1c |
-0.58; -0.66; -0.74 | — |
| SECONDARY Change From Baseline to Day 56 in Average Daily Insulin Glargine Dose |
-4.7; -4.6; -4.0 | — |
| SECONDARY Change From Baseline to Day 55 in Gastric Emptying Half Life (t1/2) |
453.56; 175.31; 130.49 | — |
| SECONDARY Change From Baseline to Day 55 in Gastric Emptying Coefficient |
-0.33; -0.34; -0.28 | — |
| SECONDARY Change From Baseline to Day 57/58 in 24-Hour Mean Heart Rate |
3.34; 9.33; 9.17 | — |
| SECONDARY Change From Baseline to Day 57/58 in 24-Hour Mean Systolic Blood Pressure and Diastolic Blood Pressure |
0.4; -0.5; -2.5; 0.8; 2.4; 1.6 | — |
| SECONDARY Change From Baseline to Day 57 in Body Weight |
-1.61; -1.78; -2.42 | — |
| SECONDARY Change From Baseline to Day 57 in Waist Circumference |
-1.40; -1.93; -2.12 | — |
| SECONDARY Change From Baseline to Day 56 in the Cumulative Score Mean on the Appetite Perception Using a Visual Analogue Scale After Standardized Solid Breakfast |
-3.7; -3.1; -1.0; 4.5; 8.9; 3.6 | — |
Eligibility Criteria
Inclusion criteria
- Participants with T2DM diagnosed at least 1 year before the screening visit.
- Treatment with neutral protamine hagedorn (NPH) or insulin glargine for at least 3 months and at a stable dose (±20%) of at least 10 IU/day (for at least 2 months prior to screening) alone or combined with a stable dose of metformin with or without dipeptidyl peptidase 4 (DPP-4) inhibitor or sulfonylurea.
- Glycosylated hemoglobin (HbA1c) ≥6.5 and ≤9.5%.
- Body mass index (BMI) between 20 and 40 kg/m^2.
Exclusion criteria
- Pregnant women or breastfeeding women.
- 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.
- Any previous treatment with lixisenatide or participation in a previous study with lixisenatide (AVE0010), and any previous treatment with liraglutide stopped for safety concern or lack of efficacy.
- Allergic reaction to any glucagon-like peptide-1 (GLP-1) agonist in the past (eg, exenatide) or to metacresol.
- History of unexplained pancreatitis, chronic pancreatitis, pancreatectomy, stomach/gastric surgery, inflammatory bowel disease.
- Personal or family history of medullary thyroid cancer (MTC) or a genetic condition that predisposes to MTC.
The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Data sourced from ClinicalTrials.gov (NCT01596504). 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.