Analysis of glucagon-like peptide 1; what to measure?

Background: Glucagon-like peptide 1 (GLP-1) is a gut hormone which acts as an incretin and is therefore of major interest in treatment of type II diabetes mellitus. GLP-1 circulates in many different forms, some of which are biologically active and others are not. Our hypothesis was that various methods to measure GLP-1 detect different forms of GLP-1, which may cause confusion when comparing results.

Methods: We compared three assays, the GLP-1 (active) ELISA (Linco research; ELISA(LINCO)), GLP-1 (total) RIA (Linco research; RIA(LINCO)) and the total GLP-1 RIA developed by the group of Holst (RIA(HOLST)) on specimens obtained during meal studies. In addition, we studied the effect of addition of a DPP-4 inhibitor.

Results: The correlation between RIA(LINCO) and ELISA(LINCO) was highest (r=0.76; n=35; p<0.01), whereas results of RIA(HOLST) correlated less with those of RIA(LINCO) and ELISA(LINCO) (r=0.35 and 0.39 respectively; n=35; p<0.05). GLP-1 results measured with ELISA(LINCO) were higher (median 28%; p<0.001) upon addition of the DPP-4 inhibitor.

Conclusion: Two commercially available GLP-1 assays do not necessarily give results equal to the well-defined GLP-1 assay developed in Copenhagen. Absolute values are also different due to differences in standardisation. Moreover, assays detect different forms of GLP-1, which hampers comparison to published data.