For people with type 1 diabetes, insulin injections can keep blood glucose levels down. To make the injection process easier for patients, chemists have been tweaking insulin’s composition. One long-lasting insulin formulation, for example, contains a hydrophobic alkyl chain that increases circulation half-life by binding to albumin and other proteins. The activity of that long-lasting insulin, however, is independent of the amount of glucose in the blood, so changes in blood sugar are not always regulated quickly enough. Daniel G. Anderson, Robert S. Langer, and coworkers at MIT set out to make long-lasting insulin that is also glucose-responsive (Proc. Natl. Acad. Sci. USA 2015, DOI: 10.1073/pnas.1424684112). They did this by adding phenylboronic acid, which binds glucose, to the end of the alkyl chain. The team tested four variants, each with a different modification to the phenylboronic acid group, on a mouse model of type 1 diabetes. The researchers administered glucose tolerance tests four hours, seven hours, and 10 hours after injecting one of the variants or native insulin. Only two of the variants continued working after 10 hours. The best one contained a fluoro-modified phenylboronic acid and worked better than the clinically available long-lasting insulin.