Impact of the Glucagon Assay when Assessing the Effect of Chronic Liraglutide Therapy on Glucagon Secretion.

Impact of the Glucagon Assay when Assessing the Effect of Chronic Liraglutide Therapy on Glucagon Secretion.

J Clin Endocrinol Metab. 2017 May 03;:

Authors: Kramer CK, Zinman B, Choi H, Connelly PW, Retnakaran R

Abstract
Context: Glucagon-like peptide-1 agonists acutely lower serum glucagon. However, in the LIraglutide and Beta-cell RepAir (LIBRA) Trial, 48-week treatment with liraglutide yielded lower/unchanged fasting glucagon but, surprisingly, enhanced post-challenge glucagonemia (measured by R&D assay).
Objective: Since differences between glucagon assays potentially could explain these unexpected findings, we have re-measured glucagon in all 1222 samples from this trial using the highly-sensitive/specific Mercodia assay to compare the findings between assays.
Design /Setting/Participants/Intervention: In LIBRA, 51 patients with type 2 diabetes of 2.6±1.9 years duration were randomized to daily subcutaneous liraglutide or placebo injection and followed for 48-weeks, with serial 75g oral glucose tolerance test (OGTT) every 12 weeks (with liraglutide/placebo last administered ∼24-hours earlier).
Outcome: Serum glucagon response was assessed at 0-,30-,60-,90- and 120-minutes on each OGTT, enabling determination of the area-under-the-glucagon-curve (AUCglucagon).
Results: With the Mercodia assay, fasting glucagon was higher in the liraglutide arm than placebo at 12-weeks (8.5±3.4 vs. 6.4±2.3 pmol/l,p=0.01), with no between-group differences at 24-,36- and 48-weeks (all p≥0.30). Unlike the R&D findings, there was no difference in AUCglucagon between the groups at any visit (all p≥0.44). Mercodia and R&D glucagon measurements correlated at post-challenge timepoints (30-minutes: r=0.69,p<0.001; 60-minutes: r=0.76,p<0.001; 90-minutes: r=0.71,p<0.001; 120-minutes: r=0.66,p<0.001) but not at fasting (r=0.26,p=0.08).
Conclusion: The Mercodia assay did not replicate the R&D glucagon findings. Though neither assay demonstrated lower post-challenge glucagonemia with chronic liraglutide last administered ∼24-hours earlier, the differential response reported by these assays precludes definitive conclusion and highlights the critical role of assay selection when measuring glucagon in clinical studies.

PMID: 28472325 [PubMed - as supplied by publisher]

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