Exenatide induces an enhanced endogenous glucagon-like peptide-1 secretory response in patients receiving basal insulin.

Parikh M, Pu J, Shen J, Kramer CK, Zinman B, Beaudry JL, Retnakaran R

The Journal of clinical endocrinology and metabolism1 Jun 2026

PMID41604435DOI10.1210/clinem/dgag033PepBankPUB-41604435

Publisher page PubMedAsk about this study

Summary

The text of this summary is not shown here, because the article license does not allow reuse. Read it at the source (opens in a new tab)

Text rights: Publisher copyright. Results still quote short attributed sentences.

Results from this study16

11 results from studies that gave the peptide. 11 results from people.

01HumanRandomized controlled trialMechanism
In adults with T2DM, glucagon response profiles did not differ between glargine/exenatide and glargine alone.
In plain wordsIn adults with T2DM, glucagon responses did not differ between glargine/exenatide and glargine alone.
Peptide
Exenatide (exendin-4)
Outcome
No significant changeGlucagon response profile
Study
n: not reported in source
Comparator
Glargine alone
Outcome group
Glycemic control · Endocrine and hormones
Studied dose
twice daily · 8 weeksAs given in this study (human).
Source sentences
Summary
There were no differences between groups in response profiles of glucagon and GIP.
2 context sentences(design, population, supporting numbers)
Summary · context
In this trial, adults with T2DM were randomized to 8-week treatment with basal insulin glargine (Glar; n = 30), glargine plus thrice-daily lispro (Glar/Lispro; n = 32), or glargine plus twice-daily exenatide (Glar/Exe; n = 31).
Summary · context
Endogenous secretion of glucagon, GIP and GLP-1 was assessed on 2-hour oral glucose tolerance test (OGTT) at baseline and after stopping therapy at 8 weeks, during which their circulating concentrations were measured every 30 minutes.
Report a problemFND-4160443501
02HumanRandomized controlled trialMechanism
In adults with T2DM, GIP response profiles did not differ between glargine/exenatide and glargine alone.
In plain wordsIn adults with T2DM, GIP responses did not differ between glargine/exenatide and glargine alone.
Peptide
Exenatide (exendin-4)
Outcome
No significant changeGIP response profile
Study
n: not reported in source
Comparator
Glargine alone
Outcome group
Glycemic control · Endocrine and hormones
Studied dose
twice daily · 8 weeksAs given in this study (human).
Source sentences
Summary
There were no differences between groups in response profiles of glucagon and GIP.
2 context sentences(design, population, supporting numbers)
Summary · context
In this trial, adults with T2DM were randomized to 8-week treatment with basal insulin glargine (Glar; n = 30), glargine plus thrice-daily lispro (Glar/Lispro; n = 32), or glargine plus twice-daily exenatide (Glar/Exe; n = 31).
Summary · context
Endogenous secretion of glucagon, GIP and GLP-1 was assessed on 2-hour oral glucose tolerance test (OGTT) at baseline and after stopping therapy at 8 weeks, during which their circulating concentrations were measured every 30 minutes.
Report a problemFND-4160443503
03HumanRandomized controlled trialMechanism
In adults with T2DM, fasting GLP-1 did not differ between glargine/exenatide and glargine alone.
In plain wordsIn adults with T2DM, fasting GLP-1 did not differ between glargine/exenatide and glargine alone.
Peptide
Exenatide (exendin-4)
Outcome
No significant changeFasting GLP-1
Study
n: not reported in source
Comparator
Glargine alone
Outcome group
Glycemic control · Endocrine and hormones
Studied dose
twice daily · 8 weeksAs given in this study (human).
Source sentences
Summary
While there were no differences in fasting GLP-1, Glar/Exe induced higher GLP-1 concentrations than the other treatments at 30 and 60 minutes post-challenge at 8 weeks (both P < .05).
2 context sentences(design, population, supporting numbers)
Summary · context
In this trial, adults with T2DM were randomized to 8-week treatment with basal insulin glargine (Glar; n = 30), glargine plus thrice-daily lispro (Glar/Lispro; n = 32), or glargine plus twice-daily exenatide (Glar/Exe; n = 31).
Summary · context
Endogenous secretion of glucagon, GIP and GLP-1 was assessed on 2-hour oral glucose tolerance test (OGTT) at baseline and after stopping therapy at 8 weeks, during which their circulating concentrations were measured every 30 minutes.
Report a problemFND-4160443505
04HumanRandomized controlled trialMechanism
In adults with T2DM, glargine/exenatide increased GLP-1 at 30 and 60 minutes versus glargine alone after treatment cessation.
In plain wordsIn adults with T2DM, glargine/exenatide increased GLP-1 after glucose compared with glargine alone after treatment stopped.
Peptide
Exenatide (exendin-4)
Outcome
IncreasePost-challenge GLP-1 concentration
Study
n: not reported in source
Comparator
Glargine alone
Outcome group
Glycemic control · Endocrine and hormones
Studied dose
twice daily · 8 weeksAs given in this study (human).
Source sentences
Summary
While there were no differences in fasting GLP-1, Glar/Exe induced higher GLP-1 concentrations than the other treatments at 30 and 60 minutes post-challenge at 8 weeks (both P < .05).
2 context sentences(design, population, supporting numbers)
Summary · context
In this trial, adults with T2DM were randomized to 8-week treatment with basal insulin glargine (Glar; n = 30), glargine plus thrice-daily lispro (Glar/Lispro; n = 32), or glargine plus twice-daily exenatide (Glar/Exe; n = 31).
Summary · context
Endogenous secretion of glucagon, GIP and GLP-1 was assessed on 2-hour oral glucose tolerance test (OGTT) at baseline and after stopping therapy at 8 weeks, during which their circulating concentrations were measured every 30 minutes.
Report a problemFND-4160443507
05HumanRandomized controlled trialMechanism
In adults with T2DM, adjusted GLP-1 was higher with glargine/exenatide than glargine alone at 30, 60 and 90 minutes.
In plain wordsIn adults with T2DM, adjusted GLP-1 after glucose was higher with glargine/exenatide than glargine alone.
Peptide
Exenatide (exendin-4)
Outcome
IncreaseBaseline-adjusted post-challenge GLP-1
Study
n: not reported in source
Comparator
Glargine alone
Outcome group
Glycemic control · Endocrine and hormones
Studied dose
twice daily · 8 weeksAs given in this study (human).
Source sentences
Summary
On the 8-week OGTT, baseline-adjusted GLP-1 was the highest in Glar/Exe at each of 30 minutes (P = .037), 60 minutes (P = .007), and 90 minutes (P = .039).
2 context sentences(design, population, supporting numbers)
Summary · context
In this trial, adults with T2DM were randomized to 8-week treatment with basal insulin glargine (Glar; n = 30), glargine plus thrice-daily lispro (Glar/Lispro; n = 32), or glargine plus twice-daily exenatide (Glar/Exe; n = 31).
Summary · context
Endogenous secretion of glucagon, GIP and GLP-1 was assessed on 2-hour oral glucose tolerance test (OGTT) at baseline and after stopping therapy at 8 weeks, during which their circulating concentrations were measured every 30 minutes.
Report a problemFND-4160443509
06HumanRandomized controlled trialMechanism
In adults with T2DM, baseline-adjusted glucagon AUC did not differ between glargine/exenatide and glargine alone.
In plain wordsIn adults with T2DM, adjusted total glucagon exposure did not differ between glargine/exenatide and glargine alone.
Peptide
Exenatide (exendin-4)
Outcome
No significant changeBaseline-adjusted glucagon AUC
Study
n: not reported in source
Comparator
Glargine alone
Outcome group
Glycemic control · Endocrine and hormones
Studied dose
twice daily · 8 weeksAs given in this study (human).
Source sentences
Summary
Unlike the respective between-group comparisons of baseline-adjusted area-under-the-curve (AUC) for glucagon and GIP (both P = NS), baseline-adjusted AUCGLP-1 at 8 weeks was the highest in Glar/Exe (P = .037).
2 context sentences(design, population, supporting numbers)
Summary · context
In this trial, adults with T2DM were randomized to 8-week treatment with basal insulin glargine (Glar; n = 30), glargine plus thrice-daily lispro (Glar/Lispro; n = 32), or glargine plus twice-daily exenatide (Glar/Exe; n = 31).
Summary · context
Endogenous secretion of glucagon, GIP and GLP-1 was assessed on 2-hour oral glucose tolerance test (OGTT) at baseline and after stopping therapy at 8 weeks, during which their circulating concentrations were measured every 30 minutes.
Report a problemFND-4160443511
07HumanRandomized controlled trialMechanism
In adults with T2DM, baseline-adjusted glucagon AUC did not differ between glargine/exenatide and glargine/lispro.
In plain wordsIn adults with T2DM, adjusted total glucagon exposure did not differ between glargine/exenatide and glargine/lispro.
Peptide
Exenatide (exendin-4)
Outcome
No significant changeBaseline-adjusted glucagon AUC
Study
n: not reported in source
Comparator
Glargine/lispro
Outcome group
Glycemic control · Endocrine and hormones
Studied dose
twice daily · 8 weeksAs given in this study (human).
Source sentences
Summary
Unlike the respective between-group comparisons of baseline-adjusted area-under-the-curve (AUC) for glucagon and GIP (both P = NS), baseline-adjusted AUCGLP-1 at 8 weeks was the highest in Glar/Exe (P = .037).
2 context sentences(design, population, supporting numbers)
Summary · context
In this trial, adults with T2DM were randomized to 8-week treatment with basal insulin glargine (Glar; n = 30), glargine plus thrice-daily lispro (Glar/Lispro; n = 32), or glargine plus twice-daily exenatide (Glar/Exe; n = 31).
Summary · context
Endogenous secretion of glucagon, GIP and GLP-1 was assessed on 2-hour oral glucose tolerance test (OGTT) at baseline and after stopping therapy at 8 weeks, during which their circulating concentrations were measured every 30 minutes.
Report a problemFND-4160443512
08HumanRandomized controlled trialMechanism
In adults with T2DM, baseline-adjusted GIP AUC did not differ between glargine/exenatide and glargine alone.
In plain wordsIn adults with T2DM, adjusted total GIP exposure did not differ between glargine/exenatide and glargine alone.
Peptide
Exenatide (exendin-4)
Outcome
No significant changeBaseline-adjusted GIP AUC
Study
n: not reported in source
Comparator
Glargine alone
Outcome group
Glycemic control · Endocrine and hormones
Studied dose
twice daily · 8 weeksAs given in this study (human).
Source sentences
Summary
Unlike the respective between-group comparisons of baseline-adjusted area-under-the-curve (AUC) for glucagon and GIP (both P = NS), baseline-adjusted AUCGLP-1 at 8 weeks was the highest in Glar/Exe (P = .037).
2 context sentences(design, population, supporting numbers)
Summary · context
In this trial, adults with T2DM were randomized to 8-week treatment with basal insulin glargine (Glar; n = 30), glargine plus thrice-daily lispro (Glar/Lispro; n = 32), or glargine plus twice-daily exenatide (Glar/Exe; n = 31).
Summary · context
Endogenous secretion of glucagon, GIP and GLP-1 was assessed on 2-hour oral glucose tolerance test (OGTT) at baseline and after stopping therapy at 8 weeks, during which their circulating concentrations were measured every 30 minutes.
Report a problemFND-4160443513
09HumanRandomized controlled trialMechanism
In adults with T2DM, baseline-adjusted GIP AUC did not differ between glargine/exenatide and glargine/lispro.
In plain wordsIn adults with T2DM, adjusted total GIP exposure did not differ between glargine/exenatide and glargine/lispro.
Peptide
Exenatide (exendin-4)
Outcome
No significant changeBaseline-adjusted GIP AUC
Study
n: not reported in source
Comparator
Glargine/lispro
Outcome group
Glycemic control · Endocrine and hormones
Studied dose
twice daily · 8 weeksAs given in this study (human).
Source sentences
Summary
Unlike the respective between-group comparisons of baseline-adjusted area-under-the-curve (AUC) for glucagon and GIP (both P = NS), baseline-adjusted AUCGLP-1 at 8 weeks was the highest in Glar/Exe (P = .037).
2 context sentences(design, population, supporting numbers)
Summary · context
In this trial, adults with T2DM were randomized to 8-week treatment with basal insulin glargine (Glar; n = 30), glargine plus thrice-daily lispro (Glar/Lispro; n = 32), or glargine plus twice-daily exenatide (Glar/Exe; n = 31).
Summary · context
Endogenous secretion of glucagon, GIP and GLP-1 was assessed on 2-hour oral glucose tolerance test (OGTT) at baseline and after stopping therapy at 8 weeks, during which their circulating concentrations were measured every 30 minutes.
Report a problemFND-4160443514
10HumanRandomized controlled trialMechanism
In adults with T2DM, adjusted GLP-1 AUC at 8 weeks was higher with glargine/exenatide than glargine alone.
In plain wordsIn adults with T2DM, adjusted total GLP-1 exposure was higher with glargine/exenatide than glargine alone.
Peptide
Exenatide (exendin-4)
Outcome
IncreaseBaseline-adjusted GLP-1 AUC
Study
n: not reported in source
Comparator
Glargine alone
Outcome group
Glycemic control · Endocrine and hormones
Studied dose
twice daily · 8 weeksAs given in this study (human).
Source sentences
Summary
Unlike the respective between-group comparisons of baseline-adjusted area-under-the-curve (AUC) for glucagon and GIP (both P = NS), baseline-adjusted AUCGLP-1 at 8 weeks was the highest in Glar/Exe (P = .037).
2 context sentences(design, population, supporting numbers)
Summary · context
In this trial, adults with T2DM were randomized to 8-week treatment with basal insulin glargine (Glar; n = 30), glargine plus thrice-daily lispro (Glar/Lispro; n = 32), or glargine plus twice-daily exenatide (Glar/Exe; n = 31).
Summary · context
Endogenous secretion of glucagon, GIP and GLP-1 was assessed on 2-hour oral glucose tolerance test (OGTT) at baseline and after stopping therapy at 8 weeks, during which their circulating concentrations were measured every 30 minutes.
Report a problemFND-4160443515
11HumanRandomized controlled trialMechanism
In adults with T2DM, adjusted GLP-1 AUC at 8 weeks was higher with glargine/exenatide than glargine/lispro.
In plain wordsIn adults with T2DM, adjusted total GLP-1 exposure was higher with glargine/exenatide than glargine/lispro.
Peptide
Exenatide (exendin-4)
Outcome
IncreaseBaseline-adjusted GLP-1 AUC
Study
n: not reported in source
Comparator
Glargine/lispro
Outcome group
Glycemic control · Endocrine and hormones
Studied dose
twice daily · 8 weeksAs given in this study (human).
Source sentences
Summary
Unlike the respective between-group comparisons of baseline-adjusted area-under-the-curve (AUC) for glucagon and GIP (both P = NS), baseline-adjusted AUCGLP-1 at 8 weeks was the highest in Glar/Exe (P = .037).
2 context sentences(design, population, supporting numbers)
Summary · context
In this trial, adults with T2DM were randomized to 8-week treatment with basal insulin glargine (Glar; n = 30), glargine plus thrice-daily lispro (Glar/Lispro; n = 32), or glargine plus twice-daily exenatide (Glar/Exe; n = 31).
Summary · context
Endogenous secretion of glucagon, GIP and GLP-1 was assessed on 2-hour oral glucose tolerance test (OGTT) at baseline and after stopping therapy at 8 weeks, during which their circulating concentrations were measured every 30 minutes.
Report a problemFND-4160443516

Studies that did not test the peptide alone5

In this study, Exenatide (exendin-4) was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Exenatide (exendin-4).

12HumanNot a test of Exenatide (exendin-4) aloneRandomized controlled trialMechanism
In adults with T2DM, glucagon response profiles did not differ between glargine/exenatide and glargine/lispro.
In plain wordsIn adults with T2DM, glucagon responses did not differ between glargine/exenatide and glargine/lispro.
Peptide
Exenatide (exendin-4)
Outcome
No significant changeGlucagon response profile
Study
n: not reported in source
Comparator
Glargine/lispro
Outcome group
Glycemic control · Endocrine and hormones
Source sentences
Summary
There were no differences between groups in response profiles of glucagon and GIP.
2 context sentences(design, population, supporting numbers)
Summary · context
In this trial, adults with T2DM were randomized to 8-week treatment with basal insulin glargine (Glar; n = 30), glargine plus thrice-daily lispro (Glar/Lispro; n = 32), or glargine plus twice-daily exenatide (Glar/Exe; n = 31).
Summary · context
Endogenous secretion of glucagon, GIP and GLP-1 was assessed on 2-hour oral glucose tolerance test (OGTT) at baseline and after stopping therapy at 8 weeks, during which their circulating concentrations were measured every 30 minutes.
In this study, Exenatide (exendin-4) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Exenatide (exendin-4).
Report a problemFND-4160443502
13HumanNot a test of Exenatide (exendin-4) aloneRandomized controlled trialMechanism
In adults with T2DM, GIP response profiles did not differ between glargine/exenatide and glargine/lispro.
In plain wordsIn adults with T2DM, GIP responses did not differ between glargine/exenatide and glargine/lispro.
Peptide
Exenatide (exendin-4)
Outcome
No significant changeGIP response profile
Study
n: not reported in source
Comparator
Glargine/lispro
Outcome group
Glycemic control · Endocrine and hormones
Source sentences
Summary
There were no differences between groups in response profiles of glucagon and GIP.
2 context sentences(design, population, supporting numbers)
Summary · context
In this trial, adults with T2DM were randomized to 8-week treatment with basal insulin glargine (Glar; n = 30), glargine plus thrice-daily lispro (Glar/Lispro; n = 32), or glargine plus twice-daily exenatide (Glar/Exe; n = 31).
Summary · context
Endogenous secretion of glucagon, GIP and GLP-1 was assessed on 2-hour oral glucose tolerance test (OGTT) at baseline and after stopping therapy at 8 weeks, during which their circulating concentrations were measured every 30 minutes.
In this study, Exenatide (exendin-4) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Exenatide (exendin-4).
Report a problemFND-4160443504
14HumanNot a test of Exenatide (exendin-4) aloneRandomized controlled trialMechanism
In adults with T2DM, fasting GLP-1 did not differ between glargine/exenatide and glargine/lispro.
In plain wordsIn adults with T2DM, fasting GLP-1 did not differ between glargine/exenatide and glargine/lispro.
Peptide
Exenatide (exendin-4)
Outcome
No significant changeFasting GLP-1
Study
n: not reported in source
Comparator
Glargine/lispro
Outcome group
Glycemic control · Endocrine and hormones
Source sentences
Summary
While there were no differences in fasting GLP-1, Glar/Exe induced higher GLP-1 concentrations than the other treatments at 30 and 60 minutes post-challenge at 8 weeks (both P < .05).
2 context sentences(design, population, supporting numbers)
Summary · context
In this trial, adults with T2DM were randomized to 8-week treatment with basal insulin glargine (Glar; n = 30), glargine plus thrice-daily lispro (Glar/Lispro; n = 32), or glargine plus twice-daily exenatide (Glar/Exe; n = 31).
Summary · context
Endogenous secretion of glucagon, GIP and GLP-1 was assessed on 2-hour oral glucose tolerance test (OGTT) at baseline and after stopping therapy at 8 weeks, during which their circulating concentrations were measured every 30 minutes.
In this study, Exenatide (exendin-4) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Exenatide (exendin-4).
Report a problemFND-4160443506
15HumanNot a test of Exenatide (exendin-4) aloneRandomized controlled trialMechanism
In adults with T2DM, glargine/exenatide increased GLP-1 at 30 and 60 minutes versus glargine/lispro after treatment cessation.
In plain wordsIn adults with T2DM, glargine/exenatide increased GLP-1 after glucose compared with glargine/lispro after treatment stopped.
Peptide
Exenatide (exendin-4)
Outcome
IncreasePost-challenge GLP-1 concentration
Study
n: not reported in source
Comparator
Glargine/lispro
Outcome group
Glycemic control · Endocrine and hormones
Source sentences
Summary
While there were no differences in fasting GLP-1, Glar/Exe induced higher GLP-1 concentrations than the other treatments at 30 and 60 minutes post-challenge at 8 weeks (both P < .05).
2 context sentences(design, population, supporting numbers)
Summary · context
In this trial, adults with T2DM were randomized to 8-week treatment with basal insulin glargine (Glar; n = 30), glargine plus thrice-daily lispro (Glar/Lispro; n = 32), or glargine plus twice-daily exenatide (Glar/Exe; n = 31).
Summary · context
Endogenous secretion of glucagon, GIP and GLP-1 was assessed on 2-hour oral glucose tolerance test (OGTT) at baseline and after stopping therapy at 8 weeks, during which their circulating concentrations were measured every 30 minutes.
In this study, Exenatide (exendin-4) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Exenatide (exendin-4).
Report a problemFND-4160443508
16HumanNot a test of Exenatide (exendin-4) aloneRandomized controlled trialMechanism
In adults with T2DM, adjusted GLP-1 was higher with glargine/exenatide than glargine/lispro at 30, 60 and 90 minutes.
In plain wordsIn adults with T2DM, adjusted GLP-1 after glucose was higher with glargine/exenatide than glargine/lispro.
Peptide
Exenatide (exendin-4)
Outcome
IncreaseBaseline-adjusted post-challenge GLP-1
Study
n: not reported in source
Comparator
Glargine/lispro
Outcome group
Glycemic control · Endocrine and hormones
Source sentences
Summary
On the 8-week OGTT, baseline-adjusted GLP-1 was the highest in Glar/Exe at each of 30 minutes (P = .037), 60 minutes (P = .007), and 90 minutes (P = .039).
2 context sentences(design, population, supporting numbers)
Summary · context
In this trial, adults with T2DM were randomized to 8-week treatment with basal insulin glargine (Glar; n = 30), glargine plus thrice-daily lispro (Glar/Lispro; n = 32), or glargine plus twice-daily exenatide (Glar/Exe; n = 31).
Summary · context
Endogenous secretion of glucagon, GIP and GLP-1 was assessed on 2-hour oral glucose tolerance test (OGTT) at baseline and after stopping therapy at 8 weeks, during which their circulating concentrations were measured every 30 minutes.
In this study, Exenatide (exendin-4) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Exenatide (exendin-4).
Report a problemFND-4160443510

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

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
22 Oct 2026, 02:26 UTC
Study results updated
Version 1
21 Oct 2026, 18:59 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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