Single, dual and triple agonists: a comparison without a ranking

Single, dual and triple are useful descriptions of intended receptor activity. They are poor substitutes for an evidence appraisal. A count tells you how many named targets a pharmacological description includes, but it does not tell you the magnitude of a clinical effect, the completeness of a safety assessment or the relevance of a trial to a particular person. Those questions require a different set of columns.

Semaglutide's discovery programme centred on GLP-1 receptor agonism. Tirzepatide is described in mechanistic research as a dual GIP and GLP-1 receptor agonist. The LY3437943 discovery paper describes a triple profile including glucagon receptor activity. These examples help organise the literature; they are not the first, second and third places in a competition. Within each programme, molecular design, experimental measurements and clinical research have their own history.

A useful comparison therefore has two layers. The first records the target profile and how it was characterised. The second records the human study question: participants, comparator, outcomes, follow-up and analysis. Keeping the layers separate allows a mechanism to remain interesting without requiring it to predict a winner. It also prevents a more complex target map from being mistaken for a more complete evidence base. The worksheet below shows how to compare the research questions without turning a receptor-count table into an unsupported recommendation. The result is a clearer account of what is known, what differs and what remains open.