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Perturbations in pancreatic β‐cell mass (BCM) and function underlie the development of Diabetes Mellitus. Current treatments and analysis of BCM are limited by inadequate specificity of β‐cell targeting agents. We propose improved specificity of β‐cell agents can be obtained by targeting unique combinations of cell surface proteins that distinguish β‐cells from other cells within the abdomen. We synthesized a multivalent ligand composed of two different receptor binding moieties: Glucagon Like Peptide‐1 (GLP‐1) and Glibenclamide (Glb, Sulfonyurea ligand, SUR1). Both GLP1R and SUR1 are expressed in the βTC3 cell line. The bivalent ligand binds to βTC3 cells with an apparent Km of ~10nM, and binding is right‐shifted by competition with monomeric GLP‐1 or Glb, indicating higher affinity binding is due to multivalent interactions. GLP‐1 elevates cAMP while Glb increases Ca2+in β‐cells. We observe that the GLP‐1/Glb elicits a half maximal Ca 2+response at ~10nM reflecting its Km but the magnitude of the Ca 2+ response was at least 10X less than monomeric Glb. Unlike the Ca 2+response, cAMP production was depressed by only ~20% compared to monomeric GLP‐1. Although signaling is depressed, glucose activated insulin secretion is potentiated to similar levels by both monomeric GLP‐1 and GLP1/Glb. Our findings indicate that multivalent ligands may provide cell type specific agents with tunable functional behavior.Supported by Juvenile Diabetes Research Foundation.