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Unfortunately, currently available formulations require burdensome separate injections at mealtimes and have disparate pharmacokinetics that do not mimic endogenous co\u2010secretion. Here, amphiphilic acrylamide copolymers are used to create a stable co\u2010formulation of monomeric insulin and amylin analogues (lispro and pramlintide) with synchronous pharmacokinetics and ultra\u2010rapid action. The co\u2010formulation is stable for over 16 h under stressed aging conditions, whereas commercial insulin lispro (Humalog) aggregates in 8 h. The faster pharmacokinetics of monomeric insulin in this co\u2010formulation result in increased insulin\u2013pramlintide overlap of 75 \u00b1 6% compared to only 47 \u00b1 7% for separate injections. The co\u2010formulation results in similar delay in gastric emptying compared to pramlintide delivered separately. In a glucose challenge, in rats, the co\u2010formulation reduces deviation from baseline glucose compared to insulin only, or separate insulin and pramlintide administrations. Further, comparison of interspecies pharmacokinetics of monomeric pramlintide suggests that pharmacokinetics observed for the co\u2010formulation will be well preserved in future translation to humans. Together these results suggest that the co\u2010formulation has the potential to improve mealtime glucose management and reduce patient burden in the treatment of diabetes.<\/jats:p>","DOI":"10.1002\/advs.202101575","type":"journal-article","created":{"date-parts":[[2021,9,9]],"date-time":"2021-09-09T12:25:01Z","timestamp":1631190301000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Ultra\u2010Fast Insulin\u2013Pramlintide Co\u2010Formulation for Improved Glucose Management in Diabetic Rats"],"prefix":"10.1002","volume":"8","author":[{"given":"Caitlin L.","family":"Maikawa","sequence":"first","affiliation":[{"name":"Department of Bioengineering Stanford University  Stanford CA 94305 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peyton C.","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Bioengineering Stanford University  Stanford CA 94305 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric T.","family":"Vuong","sequence":"additional","affiliation":[{"name":"Department of Bioengineering Stanford University  Stanford CA 94305 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leslee T.","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Bioengineering Stanford University  Stanford CA 94305 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph L.","family":"Mann","sequence":"additional","affiliation":[{"name":"Department of Materials Science &amp; 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