Exenatide and glucagon co-infusion increases myocardial glucose uptake and improves markers of diastolic dysfunction in adults with type 2 diabetes.

Goodman J, Schain M, Di Stefano G, Lupson V, Horn T, Hill M, Manavaki R, Fryer TD, Bumanlag-Amis E, Jalaludeen N, Jermutus L, Johansson E and 7 more

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Heurling K, Haraldsson H, Evans M, Cheriyan J, Johansson L, Ambery P, Wilkinson IB

Scientific reports1 Jul 2025Cited by 1 (Europe PMC)

PMID40593987PMCIDPMC12217732DOI10.1038/s41598-025-04559-3PepBankPUB-40593987

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Summary

Type 2 diabetes (T2D) significantly increases the risk of heart failure, a major cause of hospitalisation and increased morbidity and mortality. Dual and multi-agonist synthetic peptides at the GLP-1 and glucagon receptor are in clinical development as potential new treatments for a range of chronic metabolic conditions including T2D. Here, we aimed to explore the effects of GLP-1 and glucagon dual receptor agonism on myocardial glucose uptake (MGU) and myocardial function in T2D. Eight adults with a mean age of 52 ± 12 years and body mass index 31 ± 4 kg/m² attended three randomised infusion visits using combinations of 0.9% saline, glucagon (12.5 ng/kg/min) and exenatide:glucagon co-infusion (exenatide loading dose 50 ng/min for 30 min then 25 ng/min). MGU and myocardial function were assessed using ¹⁸F-FDG PET-MRI. MGU increased in n = 7/8 (88%) participants from a median of 9.2 × 10^-3 µmol/g/min (IQR 0.33-19 × 10^-3 µmol/g/min) with saline, to 20 × 10^-3 µmol/g/min (5.4-98 × 10^-3 µmol/g/min) with exenatide:glucagon, n = 8, z = 2.24, r = 0.79, P < 0.05. Exenatide:glucagon significantly increased the median left ventricular global peak diastolic circumferential strain rate from 0.619 1/s (0.580-0.716 1/s) to 0.686 1/s (0.644-0.737 1/s) n = 8, z = 2.37, r = 0.84, P < 0.05. Left ventricular global longitudinal contraction (as a measure global longitudinal strain) numerically increased by 0.6%, from - 16.0% with saline (-14.0-[-16.7]%) to -16.6% with exenatide:glucagon (-14.1-[-17.6]%), n = 8, z=-1.54, r=-0.54, P = 0.123. Further studies are required to explore whether GLP-1/glucagon dual receptor agonists have a role to play in reducing cardiovascular risk and attenuating heart failure related outcomes in patients with chronic metabolic conditions such as T2D.

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

Results from this study3

No result from this study comes from a test of the peptide.

Studies that did not test the peptide alone3

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).

01HumanNot a test of Exenatide (exendin-4) aloneRandomized controlled trialEfficacy outcome
In adults with T2D, exenatide/glucagon co-infusion increased myocardial glucose uptake versus saline in 7/8 (88%) participants.
In plain wordsIn adults with T2D, exenatide/glucagon co-infusion increased heart muscle glucose uptake compared with saline.
Peptide
Exenatide (exendin-4)
Outcome
IncreaseMyocardial glucose uptake
Study
n = 8
Comparator
Saline
Outcome group
Heart function · Cardiovascular
Measurements
Participants with increased myocardial glucose uptake
7 participants
exenatide/glucagon versus saline
Participants with increased myocardial glucose uptake
88%
exenatide/glucagon versus saline
Median myocardial glucose uptake
9.2 ×10^-3 µmol/g/min
saline
Median myocardial glucose uptake
20 ×10^-3 µmol/g/min
exenatide:glucagon
Source sentences
Summary
MGU increased in n = 7/8 (88%) participants from a median of 9.2 × 10^-3 µmol/g/min (IQR 0.33-19 × 10^-3 µmol/g/min) with saline, to 20 × 10^-3 µmol/g/min (5.4-98 × 10^-3 µmol/g/min) with exenatide:glucagon, n = 8, z = 2.24, r = 0.79, P < 0.05.
2 context sentences(design, population, supporting numbers)
Summary · context
Eight adults with a mean age of 52 ± 12 years and body mass index 31 ± 4 kg/m² attended three randomised infusion visits using combinations of 0.9% saline, glucagon (12.5 ng/kg/min) and exenatide:glucagon co-infusion (exenatide loading dose 50 ng/min for 30 min then 25 ng/min).
Summary · context
MGU and myocardial function were assessed using ¹⁸F-FDG PET-MRI.
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).
Show in the study text Report a problemFND-4059398701
02HumanNot a test of Exenatide (exendin-4) aloneRandomized controlled trialEfficacy outcome
In adults with T2D, exenatide/glucagon co-infusion increased left ventricular peak diastolic circumferential strain rate compared with saline.
In plain wordsIn adults with T2D, exenatide/glucagon co-infusion increased a measure of heart muscle relaxation compared with saline.
Peptide
Exenatide (exendin-4)
Outcome
IncreaseLeft ventricular peak diastolic circumferential strain rate
Study
n = 8
Comparator
Saline
Outcome group
Heart function · Cardiovascular
Measurements
Peak diastolic circumferential strain rate
0.619 1/s
saline
Peak diastolic circumferential strain rate
0.686 1/s
exenatide/glucagon
Source sentences
Summary
Exenatide:glucagon significantly increased the median left ventricular global peak diastolic circumferential strain rate from 0.619 1/s (0.580-0.716 1/s) to 0.686 1/s (0.644-0.737 1/s) n = 8, z = 2.37, r = 0.84, P < 0.05.
2 context sentences(design, population, supporting numbers)
Summary · context
Eight adults with a mean age of 52 ± 12 years and body mass index 31 ± 4 kg/m² attended three randomised infusion visits using combinations of 0.9% saline, glucagon (12.5 ng/kg/min) and exenatide:glucagon co-infusion (exenatide loading dose 50 ng/min for 30 min then 25 ng/min).
Summary · context
MGU and myocardial function were assessed using ¹⁸F-FDG PET-MRI.
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).
Show in the study text Report a problemFND-4059398702
03HumanNot a test of Exenatide (exendin-4) aloneRandomized controlled trialEfficacy outcome
In adults with T2D, exenatide/glucagon co-infusion numerically increased longitudinal contraction versus saline, without statistical significance.
In plain wordsIn adults with T2D, exenatide/glucagon co-infusion did not significantly change a measure of heart contraction compared with saline.
Peptide
Exenatide (exendin-4)
Outcome
No significant changeLeft ventricular global longitudinal strain
Study
n = 8
Comparator
Saline
Outcome group
Heart function · Cardiovascular
Measurements
Global longitudinal strain
−16%
saline
Global longitudinal strain
−16.6%
exenatide/glucagon
Change in global longitudinal strain
0.6%
exenatide:glucagon versus saline
Source sentences
Summary
Left ventricular global longitudinal contraction (as a measure global longitudinal strain) numerically increased by 0.6%, from - 16.0% with saline (-14.0-[-16.7]%) to -16.6% with exenatide:glucagon (-14.1-[-17.6]%), n = 8, z=-1.54, r=-0.54, P = 0.123.
2 context sentences(design, population, supporting numbers)
Summary · context
Eight adults with a mean age of 52 ± 12 years and body mass index 31 ± 4 kg/m² attended three randomised infusion visits using combinations of 0.9% saline, glucagon (12.5 ng/kg/min) and exenatide:glucagon co-infusion (exenatide loading dose 50 ng/min for 30 min then 25 ng/min).
Summary · context
MGU and myocardial function were assessed using ¹⁸F-FDG PET-MRI.
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).
Show in the study text Report a problemFND-4059398703

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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

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