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In L-cells of the lower intestine and colon the proprotein convertase subtilisin/kexin type 1 (or PCSK1/PC1) cleaves after single or double basic amino acids to liberate glicentin (amino acids 21-89 in proglucagon), oxyntomodulin (amino acids 53-89 in proglucagon), GLP-1 (amino acids 92-128 in proglucagon), and GLP-2 (amino acids 146-178 in proglucagon) (see UniProt P01275)

There may also be a mismatch between the drug mechanism and the disease driver

Think of it like stretched-out pantyhose

Journal of Pharmaceutical and Biomedical Analysis, Jun 15, 2026

Statistical Methods Change from baseline in SGRQ Total score and each component score were analyzed using analysis of covariance, with change from baseline as the response variable and with factors for treatment group, high-risk CV comorbidities (yes/no), background LABA use (yes/no), and baseline score as covariates