Exenatide for diagnosing endogenous hyperinsulinemic hypoglycemia: a randomized placebo-controlled, double-blind, cross-over proof-of-principle study.

Hepprich M, Romberg C, Mudry J, Refardt J, Wild D, Antwi K, Christ E

European journal of endocrinology1 Jul 2025Cited by 2 (Europe PMC)

PMID40747712DOI10.1093/ejendo/lvaf153PepBankPUB-40747712

Publisher page PubMedAsk about this study

Summary

ObjectiveThe 72 h fasting test, gold standard for diagnosing endogenous hyperinsulinemic hypoglycemia (EHH), is cumbersome and costly. We evaluated exenatide, a GLP-1 receptor agonist, as a faster, less burdensome alternative diagnostic tool.Design and methodsIn this prospective, placebo-controlled, double-blind, randomized cross-over, proof-of-principle study, 10 μg intravenous exenatide was compared to placebo in 14 patients with confirmed EHH in a fasting test. Fourteen matched controls received 10 μg exenatide unblinded. Clinical monitoring and measurements of glucose, insulin, C-peptide, and proinsulin were performed for 4 h. Follow-up for EHH patients included imaging and histology.ResultsExenatide induced diagnostic hypoglycemia in 6 of 14 EHH patients (42%) compared to none with placebo (P = .005). In patients with EHH, glucose nadir occurred earlier after exenatide (67 min [95% CI 50-142] vs 210 min [95% CI 174-219], P < .0001) and at lower glucose levels (2.68 mmol/L [95% CI 2.26-3.02] vs 3.2 mmol/L [95% CI 2.92-3.77], P < .0001) compared to placebo. Proinsulin levels 120 min post-exenatide were higher in patients with EHH [69 pmol/L (95% CI 3.8-232)] compared to controls [9 pmol/L (95% CI 4.5-16.9), P = .0001]. Compared to the fasting test, exenatide significantly shortened time to hypoglycemia (1.38 h [95% CI .67-2.99] vs 12 h [95% CI 1.44-36.1], P = .032). Exenatide was well tolerated and preferred by patients over the fasting test.ConclusionsExenatide is a promising, faster, less cumbersome, and less expensive diagnostic tool for EHH compared to the fasting test. Larger trials are warranted to confirm its diagnostic utility. Trial Registration ClinicalTrials.gov (NCT04909333).

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

Results from this study7

7 results from studies that gave the peptide. 7 results from people.

01HumanRandomized controlled trialActivity measurement
In patients with endogenous hyperinsulinemic hypoglycemia, exenatide induced diagnostic hypoglycemia in 42%, versus none with placebo.
In plain wordsIn patients with excess insulin-related low blood sugar, exenatide triggered diagnostic low blood sugar more often than placebo.
Peptide
Exenatide (exendin-4)
Outcome
IncreaseDiagnostic hypoglycemia
Study
n = 14
Comparator
Placebo
Outcome group
Glycemic control · Metabolic and weight
Studied dose
10 μg · intravenousAs given in this study (human).
Measurements
Diagnostic hypoglycemia
42%
Exenatide
Patients with diagnostic hypoglycemia
6 patients
Exenatide (of 14 patients with EHH)
Source sentences
Summary
Exenatide induced diagnostic hypoglycemia in 6 of 14 EHH patients (42%) compared to none with placebo (P = .005).
2 context sentences(design, population, supporting numbers)
Summary · context
In this prospective, placebo-controlled, double-blind, randomized cross-over, proof-of-principle study, 10 μg intravenous exenatide was compared to placebo in 14 patients with confirmed EHH in a fasting test.
Summary · context
Fourteen matched controls received 10 μg exenatide unblinded.
Show in the study text Report a problemFND-4074771201
02HumanRandomized controlled trialActivity measurement
In patients with endogenous hyperinsulinemic hypoglycemia, glucose nadir occurred earlier after exenatide than placebo.
In plain wordsIn patients with excess insulin-related low blood sugar, blood sugar reached its lowest level sooner with exenatide than placebo.
Peptide
Exenatide (exendin-4)
Outcome
DecreaseTime to glucose nadir
Study
n = 14
Comparator
Placebo
Outcome group
Glycemic control · Metabolic and weight
Studied dose
10 μg · intravenousAs given in this study (human).
Measurements
Time to glucose nadir
67 min
Exenatide
Time to glucose nadir
210 min
Placebo
Source sentences
Summary
In patients with EHH, glucose nadir occurred earlier after exenatide (67 min [95% CI 50-142] vs 210 min [95% CI 174-219], P < .0001) and at lower glucose levels (2.68 mmol/L [95% CI 2.26-3.02] vs 3.2 mmol/L [95% CI 2.92-3.77], P < .0001) compared to placebo.
2 context sentences(design, population, supporting numbers)
Summary · context
In this prospective, placebo-controlled, double-blind, randomized cross-over, proof-of-principle study, 10 μg intravenous exenatide was compared to placebo in 14 patients with confirmed EHH in a fasting test.
Summary · context
Fourteen matched controls received 10 μg exenatide unblinded.
Show in the study text Report a problemFND-4074771202
03HumanRandomized controlled trialActivity measurement
In patients with endogenous hyperinsulinemic hypoglycemia, glucose nadir was lower after exenatide than placebo.
In plain wordsIn patients with excess insulin-related low blood sugar, blood sugar reached a lower minimum with exenatide than placebo.
Peptide
Exenatide (exendin-4)
Outcome
DecreaseGlucose nadir
Study
n = 14
Comparator
Placebo
Outcome group
Glycemic control · Metabolic and weight
Studied dose
10 μg · intravenousAs given in this study (human).
Measurements
Glucose nadir
2.68 mmol/L
Exenatide
Glucose nadir
3.2 mmol/L
Placebo
Source sentences
Summary
In patients with EHH, glucose nadir occurred earlier after exenatide (67 min [95% CI 50-142] vs 210 min [95% CI 174-219], P < .0001) and at lower glucose levels (2.68 mmol/L [95% CI 2.26-3.02] vs 3.2 mmol/L [95% CI 2.92-3.77], P < .0001) compared to placebo.
2 context sentences(design, population, supporting numbers)
Summary · context
In this prospective, placebo-controlled, double-blind, randomized cross-over, proof-of-principle study, 10 μg intravenous exenatide was compared to placebo in 14 patients with confirmed EHH in a fasting test.
Summary · context
Fourteen matched controls received 10 μg exenatide unblinded.
Show in the study text Report a problemFND-4074771203
04HumanRandomized controlled trialSafety outcome
In the diagnostic study, exenatide was well tolerated.
In plain wordsIn the diagnostic study, patients tolerated exenatide well.
Peptide
Exenatide (exendin-4)
Outcome
Not applicableTolerability
Study
n: not reported in source
Outcome group
Adverse events · Whole body
Studied dose
10 μg · intravenousAs given in this study (human).
Source sentences
Summary
Exenatide was well tolerated and preferred by patients over the fasting test.
2 context sentences(design, population, supporting numbers)
Summary · context
In this prospective, placebo-controlled, double-blind, randomized cross-over, proof-of-principle study, 10 μg intravenous exenatide was compared to placebo in 14 patients with confirmed EHH in a fasting test.
Summary · context
Fourteen matched controls received 10 μg exenatide unblinded.
Show in the study text Report a problemFND-4074771206
05HumanNon-randomized trialActivity measurement
After exenatide, proinsulin levels were higher in patients with endogenous hyperinsulinemic hypoglycemia than matched controls.
In plain wordsAfter exenatide, patients with excess insulin-related low blood sugar had higher proinsulin levels than matched controls.
Peptide
Exenatide (exendin-4)
Outcome
IncreaseProinsulin at 120 minutes
Study
n = 28
Comparator
Matched controls receiving exenatide
Outcome group
Glycemic control · Metabolic and weight
Studied dose
10 μg · intravenousAs given in this study (human).
Measurements
Proinsulin
69 pmol/L
Patients at 120 minutes
Proinsulin
9 pmol/L
Controls at 120 minutes
Source sentences
Summary
Proinsulin levels 120 min post-exenatide were higher in patients with EHH [69 pmol/L (95% CI 3.8-232)] compared to controls [9 pmol/L (95% CI 4.5-16.9), P = .0001].
2 context sentences(design, population, supporting numbers)
Summary · context
In this prospective, placebo-controlled, double-blind, randomized cross-over, proof-of-principle study, 10 μg intravenous exenatide was compared to placebo in 14 patients with confirmed EHH in a fasting test.
Summary · context
Fourteen matched controls received 10 μg exenatide unblinded.
Show in the study text Report a problemFND-4074771204
06HumanNon-randomized trialActivity measurement
In patients with endogenous hyperinsulinemic hypoglycemia, exenatide shortened time to hypoglycemia compared with the fasting test.
In plain wordsIn patients with excess insulin-related low blood sugar, exenatide produced low blood sugar sooner than the fasting test.
Peptide
Exenatide (exendin-4)
Outcome
DecreaseTime to hypoglycemia
Study
n = 14
Comparator
Fasting test
Outcome group
Glycemic control · Metabolic and weight
Studied dose
10 μg · intravenousAs given in this study (human).
Measurements
Time to hypoglycemia
1.38 h
Exenatide
Time to hypoglycemia
12 h
Fasting test
Source sentences
Summary
Compared to the fasting test, exenatide significantly shortened time to hypoglycemia (1.38 h [95% CI .67-2.99] vs 12 h [95% CI 1.44-36.1], P = .032).
2 context sentences(design, population, supporting numbers)
Summary · context
In this prospective, placebo-controlled, double-blind, randomized cross-over, proof-of-principle study, 10 μg intravenous exenatide was compared to placebo in 14 patients with confirmed EHH in a fasting test.
Summary · context
Fourteen matched controls received 10 μg exenatide unblinded.
Show in the study text Report a problemFND-4074771205
07HumanNon-randomized trialOther
Patients preferred exenatide to the fasting test for diagnosing endogenous hyperinsulinemic hypoglycemia.
In plain wordsPatients preferred exenatide to the fasting test for diagnosing excess insulin-related low blood sugar.
Peptide
Exenatide (exendin-4)
Outcome
IncreasePatient preference
Study
n: not reported in source
Comparator
Fasting test
Outcome group
Patient-reported outcomes · Whole body
Studied dose
10 μg · intravenousAs given in this study (human).
Source sentences
Summary
Exenatide was well tolerated and preferred by patients over the fasting test.
2 context sentences(design, population, supporting numbers)
Summary · context
In this prospective, placebo-controlled, double-blind, randomized cross-over, proof-of-principle study, 10 μg intravenous exenatide was compared to placebo in 14 patients with confirmed EHH in a fasting test.
Summary · context
Fourteen matched controls received 10 μg exenatide unblinded.
Show in the study text Report a problemFND-4074771207

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)

CompletedNot applicableNCT04909333

Exenatide-test for Diagnosing Endogenous Hyperinsulinemic Hypoglycemia

University Hospital, Basel, Switzerlandn = 2929 Apr 2021 to 30 Apr 2024

Endogenous Hyperinsulinism

Trial page ClinicalTrials.govUpdated 8 May 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
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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