Scientists made lab tests that can spot antibodies that block semaglutide (a weight‑loss/diabetes drug) and natural GLP‑1 more easily and even when the drug is present. They tweaked the test conditions, sample handling, and control antibodies to get better detection limits.

The purpose of this work was to optimize the sensitivity and the drug tolerance of two cell-based assays for the detection of neutralizing antibodies (nAbs) to semaglutide (a GLP-1 analogue) and to endogenous GLP-1. The two assays were developed and validated in three distinct iterations. Enhancements in sensitivity and drug tolerance were achieved through platform optimization, sample pre-treatment and the alteration of control antibodies. The sensitivity and drug tolerance improved gradually with the different versions of the assays. For detection of nAbs to semaglutide, sensitivity was improved from 3,400 ng to 98 ng/ml antibody, and drug tolerance was improved from 2.5 nM semaglutide when detecting 3,400 ng/ml antibodies to 4.8-5.6 nM semaglutide when detecting 1,000 ng/ml antibody. For the endogenous GLP-1 assay, sensitivity was improved from 6,900 ng/ml to 46 ng/ml antibody, and drug tolerance improved from 1.0 nM semaglutide when detecting antibody concentration of 8,800 ng/ml to 2.5 nM semaglutide when detecting 1,000 ng/ml antibody. Key factors for enhancing the sensitivity and drug tolerance of the assays included the concentration of the drug standard for receptor activation, pre-treatment of the samples, and better understanding of the binding properties of the control antibody.