Exenatide for diagnosing endogenous hyperinsulinemic hypoglycaemia - a randomised placebo-controlled, double-blind, cross-over proof-of-principle study - fast study

Matthias Hepprich; Christina Romberg; Jonathan Mudry; Refardt Julie Celine; Damian Wild; Kwadwo Antwi; Emanuel Christ

doi:10.1530/endoabs.110.P896

P896

Prev Next

Section Contents Cite

Endocrine Abstracts (2025) 110 P896 | DOI: 10.1530/endoabs.110.P896

ECEESPE2025 Poster Presentations Pituitary, Neuroendocrinology and Puberty (162 abstracts)

Exenatide for diagnosing endogenous hyperinsulinemic hypoglycaemia - a randomised placebo-controlled, double-blind, cross-over proof-of-principle study - fast study

Matthias Hepprich ^1,2 , Christina Romberg ³ , Jonathan Mudry ⁴ , Julie Celine Refardt ^3,5 , Damian Wild ³ , Kwadwo Antwi ⁶ & Emanuel Christ ²

Author affiliations

¹Cantonal Hospital Olten, Metabolic Center, Olten, Switzerland; ²University of Basel, Basel, Switzerland; ³University of Basel, Division of Nuclear Medicine, Basel, Switzerland; ⁴Hôpital du Valais, Sion, Switzerland; ⁵Erasmus Medical Center, Department of Internal Medicine, Section of Endocrinology, Rotterdam, Netherlands; ⁶St. Claraspital, Department of Nuclear Medicine, Basel, Switzerland

JOINT1104

Background: The 72-hour fasting test, the gold standard for diagnosing endogenous hyperinsulinemic hypoglycaemia (EHH), is cumbersome and costly. This study evaluated exenatide, a GLP-1 receptor agonist, as a faster, less burdensome alternative diagnostic tool.

Methods: In this prospective, placebo-controlled, double-blind, randomised cross-over, proof-of-principle study, 14 patients with confirmed EHH in a 72-hour fasting test received in a randomized order 10 μg intravenous exenatide or placebo after at least 24 hours in between. Fourteen matched controls received 10 μg exenatide in an open-label design. Clinical monitoring and measurements of glucose, insulin, C-peptide, and proinsulin were performed for 4 hours. Follow-up included imaging and histological confirmation for EHH patients.

Findings: Exenatide induced diagnostic hypoglycaemia in 6 of 14 EHH patients (42%) compared to none with placebo (P = 0•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 < 0•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 < 0•0001) compared to placebo. Proinsulin levels at 120 minutes 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 = 0•0001). Compared to the fasting test, exenatide significantly shortened time to hypoglycaemia compared to the fasting test (1•38 hours [95% CI 0•67–2•99] vs. 12 hours [95% CI 1•44–36•1] respectively, P = 0•032). All patients preferred the exenatide test over the fasting test. Exenatide was well tolerated.

Interpretation: Intravenous exenatide 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.