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

Objective:

The 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 Methods:

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. 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. 

Results: 

Exenatide 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 (67min [95% CI 50-142] vs 210min [95% CI 174-219], P <. 0001) and at lower glucose levels (2.68mmol/L [95% CI 2.26-3.02] vs 3.2mmol/L [95% CI 2.92-3.77], P <. 0001) compared to placebo. Proinsulin levels 120 min post-exenatide were higher in patients with EHH [69pmol/L (95% CI 3.8-232)] compared to controls [9pmol/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. 

Conclusions: 

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.