Lixisenatide Reduces Chylomicron Triacylglycerol by Increased Clearance.

Whyte MB, Shojaee-Moradie F, Sharaf SE, Jackson NC, Fielding B, Hovorka R, Mendis J, Russell-Jones D, Umpleby AM

The Journal of clinical endocrinology and metabolism1 Feb 2019Cited by 23 (Europe PMC)

PMID30215735PMCIDPMC6300412DOI10.1210/jc.2018-01176PepBankPUB-30215735

Summary

ContextGlucagon-like peptide-1 (GLP-1) agonists control postprandial glucose and lipid excursion in type 2 diabetes; however, the mechanisms are unclear.ObjectiveTo determine the mechanisms of postprandial lipid and glucose control with lixisenatide (GLP-1 analog) in type 2 diabetes.DesignRandomized, double-blind, cross-over study.SettingCentre for Diabetes, Endocrinology, and Research, Royal Surrey County Hospital, Guildford, United Kingdom.PatientsEight obese men with type 2 diabetes [age, 57.3 ± 1.9 years; body mass index, 30.3 ± 1.0 kg/m2; glycosylated hemoglobin, 66.5 ± 2.6 mmol/mol (8.2% ± 0.3%)].InterventionsTwo metabolic studies, 4 weeks after lixisenatide or placebo, with cross-over and repetition of studies.Main outcome measuresStudy one: very-low-density lipoprotein (VLDL) and chylomicron (CM) triacylglycerol (TAG) kinetics were measured with an IV bolus of [2H5]glycerol in a 12-hour study, with hourly feeding. Oral [13C]triolein, in a single meal, labeled enterally derived TAG. Study two: glucose kinetics were measured with [U-13C]glucose in a mixed-meal (plus acetaminophen to measure gastric emptying) and variable IV [6,6-2H2]glucose infusion.ResultsStudy one: CM-TAG (but not VLDL-TAG) pool-size was lower with lixisenatide (P = 0.046). Lixisenatide reduced CM [13C]oleate area under the curve (AUC)60-480min concentration (P = 0.048) and increased CM-TAG clearance, with no effect on CM-TAG production rate. Study two: postprandial glucose and insulin AUC0-240min were reduced with lixisenatide (P = 0.0051; P < 0.05). Total glucose production (P = 0.015), rate of glucose appearance from the meal (P = 0.0098), and acetaminophen AUC0-360min (P = 0.006) were lower with lixisenatide than with placebo.ConclusionsLixisenatide reduced [13C]oleate concentrations, derived from a single meal in CM-TAG and glucose rate of appearance from the meal through delayed gastric emptying. However, day-long CM production, measured with repeated meal feeding, was not reduced by lixisenatide and decreased CM-TAG concentration resulted from increased CM-TAG clearance.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study10

10 results from studies that gave the peptide. 10 results from people.

01HumanRandomized controlled trialEfficacy outcome
In obese men with diabetes, lixisenatide reduced CM-TAG pool size versus placebo (P = 0.046).
In plain wordsLixisenatide reduced CM-TAG pool size versus placebo in obese men with diabetes.
Peptide
Lixisenatide
Outcome
DecreaseCM-TAG pool size
Study
n = 8
Comparator
Placebo
Outcome group
Lipids · Metabolic and weight
Studied dose
Dose not stated
Measurements
P value (CM-TAG pool size)
0.046 P
lixisenatide vs placebo
Source sentences
Summary
Study one: CM-TAG (but not VLDL-TAG) pool-size was lower with lixisenatide (P = 0.046).
3 context sentences(design, population, supporting numbers)
Summary · context
Randomized, double-blind, cross-over study.
Summary · context
Eight obese men with type 2 diabetes [age, 57.3 ± 1.9 years; body mass index, 30.3 ± 1.0 kg/m2; glycosylated hemoglobin, 66.5 ± 2.6 mmol/mol (8.2% ± 0.3%)].
Summary · context
Two metabolic studies, 4 weeks after lixisenatide or placebo, with cross-over and repetition of studies.
Show in the study text Report a problemFND-3021573501
02HumanRandomized controlled trialEfficacy outcome
In obese men with diabetes, lixisenatide did not reduce VLDL-TAG pool size versus placebo.
In plain wordsLixisenatide did not reduce VLDL-TAG pool size versus placebo in obese men with diabetes.
Peptide
Lixisenatide
Outcome
No significant changeVLDL-TAG pool size
Study
n = 8
Comparator
Placebo
Outcome group
Lipids · Metabolic and weight
Studied dose
Dose not stated
Source sentences
Summary
Study one: CM-TAG (but not VLDL-TAG) pool-size was lower with lixisenatide (P = 0.046).
3 context sentences(design, population, supporting numbers)
Summary · context
Randomized, double-blind, cross-over study.
Summary · context
Eight obese men with type 2 diabetes [age, 57.3 ± 1.9 years; body mass index, 30.3 ± 1.0 kg/m2; glycosylated hemoglobin, 66.5 ± 2.6 mmol/mol (8.2% ± 0.3%)].
Summary · context
Two metabolic studies, 4 weeks after lixisenatide or placebo, with cross-over and repetition of studies.
Show in the study text Report a problemFND-3021573502
03HumanRandomized controlled trialEfficacy outcome
In obese men with diabetes, lixisenatide reduced CM oleate concentration AUC versus placebo (P = 0.048).
In plain wordsLixisenatide reduced CM oleate concentration AUC versus placebo in obese men with diabetes.
Peptide
Lixisenatide
Outcome
DecreaseCM oleate concentration AUC
Study
n = 8
Comparator
Placebo
Outcome group
Lipids · Metabolic and weight
Studied dose
Dose not stated
Measurements
P value (CM [13C]oleate AUC60-480min)
0.048 P
lixisenatide vs placebo
Source sentences
Summary
Lixisenatide reduced CM [13C]oleate area under the curve (AUC)60-480min concentration (P = 0.048) and increased CM-TAG clearance, with no effect on CM-TAG production rate.
3 context sentences(design, population, supporting numbers)
Summary · context
Randomized, double-blind, cross-over study.
Summary · context
Eight obese men with type 2 diabetes [age, 57.3 ± 1.9 years; body mass index, 30.3 ± 1.0 kg/m2; glycosylated hemoglobin, 66.5 ± 2.6 mmol/mol (8.2% ± 0.3%)].
Summary · context
Two metabolic studies, 4 weeks after lixisenatide or placebo, with cross-over and repetition of studies.
Show in the study text Report a problemFND-3021573503
04HumanRandomized controlled trialEfficacy outcome
In obese men with diabetes, lixisenatide increased CM-TAG clearance versus placebo.
In plain wordsLixisenatide increased CM-TAG clearance versus placebo in obese men with diabetes.
Peptide
Lixisenatide
Outcome
IncreaseCM-TAG clearance
Study
n = 8
Comparator
Placebo
Outcome group
Lipids · Metabolic and weight
Studied dose
Dose not stated
Source sentences
Summary
Lixisenatide reduced CM [13C]oleate area under the curve (AUC)60-480min concentration (P = 0.048) and increased CM-TAG clearance, with no effect on CM-TAG production rate.
3 context sentences(design, population, supporting numbers)
Summary · context
Randomized, double-blind, cross-over study.
Summary · context
Eight obese men with type 2 diabetes [age, 57.3 ± 1.9 years; body mass index, 30.3 ± 1.0 kg/m2; glycosylated hemoglobin, 66.5 ± 2.6 mmol/mol (8.2% ± 0.3%)].
Summary · context
Two metabolic studies, 4 weeks after lixisenatide or placebo, with cross-over and repetition of studies.
Show in the study text Report a problemFND-3021573504
05HumanRandomized controlled trialEfficacy outcome
In obese men with diabetes, lixisenatide did not affect CM-TAG production rate versus placebo.
In plain wordsLixisenatide did not affect CM-TAG production rate versus placebo in obese men with diabetes.
Peptide
Lixisenatide
Outcome
No significant changeCM-TAG production rate
Study
n = 8
Comparator
Placebo
Outcome group
Lipids · Metabolic and weight
Studied dose
Dose not stated
Source sentences
Summary
Lixisenatide reduced CM [13C]oleate area under the curve (AUC)60-480min concentration (P = 0.048) and increased CM-TAG clearance, with no effect on CM-TAG production rate.
3 context sentences(design, population, supporting numbers)
Summary · context
Randomized, double-blind, cross-over study.
Summary · context
Eight obese men with type 2 diabetes [age, 57.3 ± 1.9 years; body mass index, 30.3 ± 1.0 kg/m2; glycosylated hemoglobin, 66.5 ± 2.6 mmol/mol (8.2% ± 0.3%)].
Summary · context
Two metabolic studies, 4 weeks after lixisenatide or placebo, with cross-over and repetition of studies.
Show in the study text Report a problemFND-3021573505
06HumanRandomized controlled trialEfficacy outcome
In obese men with diabetes, lixisenatide reduced postprandial glucose AUC versus placebo (P = 0.0051).
In plain wordsLixisenatide reduced postprandial glucose AUC versus placebo in obese men with diabetes.
Peptide
Lixisenatide
Outcome
DecreasePostprandial glucose AUC
Study
n = 8
Comparator
Placebo
Outcome group
Glycemic control · Metabolic and weight
Studied dose
Dose not stated
Measurements
P value (postprandial glucose AUC0-240min)
0.0051 P
lixisenatide vs placebo
Source sentences
Summary
Study two: postprandial glucose and insulin AUC0-240min were reduced with lixisenatide (P = 0.0051; P < 0.05).
3 context sentences(design, population, supporting numbers)
Summary · context
Randomized, double-blind, cross-over study.
Summary · context
Eight obese men with type 2 diabetes [age, 57.3 ± 1.9 years; body mass index, 30.3 ± 1.0 kg/m2; glycosylated hemoglobin, 66.5 ± 2.6 mmol/mol (8.2% ± 0.3%)].
Summary · context
Two metabolic studies, 4 weeks after lixisenatide or placebo, with cross-over and repetition of studies.
Show in the study text Report a problemFND-3021573506
07HumanRandomized controlled trialEfficacy outcome
In obese men with diabetes, lixisenatide reduced postprandial insulin AUC versus placebo (P < 0.05).
In plain wordsLixisenatide reduced postprandial insulin AUC versus placebo in obese men with diabetes.
Peptide
Lixisenatide
Outcome
DecreasePostprandial insulin AUC
Study
n = 8
Comparator
Placebo
Outcome group
Glycemic control · Metabolic and weight
Studied dose
Dose not stated
Measurements
P value (postprandial insulin AUC0-240min)
< 0.05 P
lixisenatide vs placebo
Source sentences
Summary
Study two: postprandial glucose and insulin AUC0-240min were reduced with lixisenatide (P = 0.0051; P < 0.05).
3 context sentences(design, population, supporting numbers)
Summary · context
Randomized, double-blind, cross-over study.
Summary · context
Eight obese men with type 2 diabetes [age, 57.3 ± 1.9 years; body mass index, 30.3 ± 1.0 kg/m2; glycosylated hemoglobin, 66.5 ± 2.6 mmol/mol (8.2% ± 0.3%)].
Summary · context
Two metabolic studies, 4 weeks after lixisenatide or placebo, with cross-over and repetition of studies.
Show in the study text Report a problemFND-3021573507
08HumanRandomized controlled trialEfficacy outcome
In obese men with diabetes, lixisenatide reduced total glucose production versus placebo (P = 0.015).
In plain wordsLixisenatide reduced total glucose production versus placebo in obese men with diabetes.
Peptide
Lixisenatide
Outcome
DecreaseTotal glucose production
Study
n = 8
Comparator
Placebo
Outcome group
Glycemic control · Metabolic and weight
Studied dose
Dose not stated
Measurements
P value (total glucose production)
0.015 P
lixisenatide vs placebo
Source sentences
Summary
Total glucose production (P = 0.015), rate of glucose appearance from the meal (P = 0.0098), and acetaminophen AUC0-360min (P = 0.006) were lower with lixisenatide than with placebo.
3 context sentences(design, population, supporting numbers)
Summary · context
Randomized, double-blind, cross-over study.
Summary · context
Eight obese men with type 2 diabetes [age, 57.3 ± 1.9 years; body mass index, 30.3 ± 1.0 kg/m2; glycosylated hemoglobin, 66.5 ± 2.6 mmol/mol (8.2% ± 0.3%)].
Summary · context
Two metabolic studies, 4 weeks after lixisenatide or placebo, with cross-over and repetition of studies.
Show in the study text Report a problemFND-3021573508
09HumanRandomized controlled trialEfficacy outcome
In obese men with diabetes, lixisenatide reduced meal glucose appearance rate versus placebo (P = 0.0098).
In plain wordsLixisenatide reduced meal glucose appearance rate versus placebo in obese men with diabetes.
Peptide
Lixisenatide
Outcome
DecreaseMeal glucose appearance rate
Study
n = 8
Comparator
Placebo
Outcome group
Glycemic control · Metabolic and weight
Studied dose
Dose not stated
Measurements
P value (meal glucose appearance rate)
0.0098 P
lixisenatide vs placebo
Source sentences
Summary
Total glucose production (P = 0.015), rate of glucose appearance from the meal (P = 0.0098), and acetaminophen AUC0-360min (P = 0.006) were lower with lixisenatide than with placebo.
3 context sentences(design, population, supporting numbers)
Summary · context
Randomized, double-blind, cross-over study.
Summary · context
Eight obese men with type 2 diabetes [age, 57.3 ± 1.9 years; body mass index, 30.3 ± 1.0 kg/m2; glycosylated hemoglobin, 66.5 ± 2.6 mmol/mol (8.2% ± 0.3%)].
Summary · context
Two metabolic studies, 4 weeks after lixisenatide or placebo, with cross-over and repetition of studies.
Show in the study text Report a problemFND-3021573509
10HumanRandomized controlled trialEfficacy outcome
In obese men with diabetes, lixisenatide reduced acetaminophen AUC versus placebo (P = 0.006).
In plain wordsLixisenatide reduced acetaminophen AUC versus placebo in obese men with diabetes.
Peptide
Lixisenatide
Outcome
DecreaseAcetaminophen AUC
Study
n = 8
Comparator
Placebo
Outcome group
Gastrointestinal motility · Gastrointestinal
Studied dose
Dose not stated
Measurements
P value (acetaminophen AUC0-360min)
0.006 P
lixisenatide vs placebo
Source sentences
Summary
Total glucose production (P = 0.015), rate of glucose appearance from the meal (P = 0.0098), and acetaminophen AUC0-360min (P = 0.006) were lower with lixisenatide than with placebo.
3 context sentences(design, population, supporting numbers)
Summary · context
Randomized, double-blind, cross-over study.
Summary · context
Eight obese men with type 2 diabetes [age, 57.3 ± 1.9 years; body mass index, 30.3 ± 1.0 kg/m2; glycosylated hemoglobin, 66.5 ± 2.6 mmol/mol (8.2% ± 0.3%)].
Summary · context
Two metabolic studies, 4 weeks after lixisenatide or placebo, with cross-over and repetition of studies.
Show in the study text Report a problemFND-3021573510

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Registered trials1

Trials this study reports on, or that list this study as a reference. Registry data from ClinicalTrials.gov.

1 trial · 1 completed · source ClinicalTrials.gov (opens in a new tab)

CompletedPhase 4NCT02049034

Lixisenatide-The Effects on Glucose and Lipid Metabolism in Type 2 Diabetes

University of Surreyn = 8Jan 2014 to Jan 2016

Type 2 Diabetes

Trial page ClinicalTrials.govUpdated 16 Dec 2024

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
28 Oct 2026, 02:03 UTC
Study results updated
Version 1
27 Oct 2026, 16:36 UTC
First added · source update from Europe PMC

PepBank is a research reference. Talk to a doctor before you use any peptide.