Effects of GLP-1 on counter-regulatory responses during hypoglycemia after GBP surgery

in European Journal of Endocrinology

Correspondence should be addressed to J W Eriksson; Email: jan.eriksson@medsci.uu.se

*(K E Almby and N Abrahamsson contributed equally to this work)

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The aim of the study was to explore the role of GLP-1 receptor activation on the counter-regulation and symptoms of hypoglycemia in subjects who have undergone gastric bypass surgery (GBP).


Experimental hyperinsulinemic–hypoglycemic clamp study.


Twelve post-GBP subjects participated in a randomized cross-over study with two hyperinsulinemic, hypoglycemic clamps (glucose nadir 2.7 mmol/L) performed on separate days with concomitant infusions of the GLP-1 analog exenatide or with saline, respectively. Continuous measurements of metabolites and counter-regulatory hormones as well as assessments of heart rate variability and symptoms of hypoglycemia were performed throughout the clamps.


No effect of GLP-1 receptor activation on counter-regulatory hormones (glucagon, catecholamines, cortisol, GH) or glucose infusion rate was seen, but we found indications of a downregulation of the sympathetic relative to the parasympathetic nerve activity, as reflected in heart rate variability. No significant differences in symptom of hypoglycemia were observed.


Short-term exposure to a GLP-1 receptor agonist does not seem to impact the counter-regulatory hormonal and metabolic responses in post-GBP subjects during hypoglycemic conditions, suggesting that the improvement in symptomatic hypoglycemia post-GBP seen following treatment with GLP-1 receptor agonists may be mediated by mechanism not directly involved in counter-regulation.

Supplementary Materials

    • Effects of GLP-1 on counter-regulatory responses during hypoglycemia after GBP surgery
    • Supplementary Figure 1
    • Supplementary Table 1. Edinburgh Hypoglycemia Symptom Scale subdivisions and symptoms assessed. Subjects are asked to rate the follow symptoms on scales ranging from 1 (no symptoms) to 7 (maximal symptoms).
    • Supplementary Table 2: Hormone and metabolite concentrations


     European Society of Endocrinology