Dulaglutide: Difference between revisions

| structure = '''Fc-fusion construct''': two identical GLP-1 analog peptides (each modified at positions 8, 22, 36 for DPP-4 resistance and reduced immunogenicity) linked to a human IgG4 Fc fragment via a small glycine-rich peptide linker. The Fc tail drives the long half-life through FcRn recycling.<ref name="glaesner2010">Glaesner W, Vick AM, Millican R et al. (2010). Engineering and characterization of the long-acting glucagon-like peptide-1 analogue LY2189265, an Fc fusion protein. ''Diabetes Metab Res Rev'' 26(4):287–96. doi:10.1002/dmrr.1080</ref>

| mechanism = Selective long-acting agonist of the [[GLP-1 receptor]]. The Fc-IgG4 structure differentiates it pharmacokinetically (large protein cleared by FcRn-mediated recycling rather than albumin binding) but the receptor pharmacology is the standard GLP-1 RA profile.<ref name="glaesner2010"/>

| intro = Dulaglutide is a weekly subcutaneous [[GLP-1 receptor agonist]] developed by Eli Lilly, marketed as '''[[Trulicity]]''' since September 2014.<ref name="trulicity-label"/> Structurally distinct from the acylated peptide GLP-1 RAs ([[semaglutide]], [[liraglutide]]), dulaglutide is an Fc-fusion biologic — its long half-life comes from FcRn-mediated recycling rather than albumin binding.<ref name="glaesner2010"/>

Dulaglutide's principal clinical distinction is the [[REWIND trial|REWIND trial]], in which dulaglutide reduced major adverse cardiovascular events by 12% in T2DM patients ''including a majority with no prior cardiovascular disease'' — making it the first GLP-1 RA to demonstrate cardiovascular benefit in ''primary'' prevention.<ref name="rewind">Gerstein HC et al. (2019). Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND). ''Lancet'' 394(10193):121–30. doi:10.1016/S0140-6736(19)31149-3</ref>

| pharmacokinetics = The Fc-IgG4 fusion confers protection from renal filtration (~63 kDa, well above the glomerular cutoff) and triggers FcRn-mediated recycling, producing a terminal half-life of ~120 hours.<ref name="glaesner2010"/><ref name="trulicity-label"/> Cleared by proteolytic catabolism; no CYP-mediated metabolism. No dose adjustment for renal or hepatic impairment.<ref name="trulicity-label"/>

The large molecular size limits both injection-site dispersion and oral bioavailability — dulaglutide cannot be formulated for oral use.

| pharmacodynamics = At maintenance doses:

| indications = <indication ref="diabetes-type-2" author="MDElliottMD"/>

<indication ref="cv-risk-t2dm" author="MDElliottMD"/>

| dosing = <titration slug="trulicity-standard" author="MDElliottMD" title="Trulicity — standard T2DM titration">

* '''Nausea''' — usually mild-to-moderate, peaks in first 2–4 weeks<ref name="trulicity-label"/>

* '''Injection-site reactions''' — uncommon, generally mild<ref name="trulicity-label"/>

| pregnancy_details = Avoid. Animal embryofetal toxicity is documented.<ref name="trulicity-label"/> Discontinue at least 1 month before planned conception due to the ~5-day half-life. The pen contains no preservatives — single-dose only.

* Personal or family history of MTC or [[MEN2]] — '''contraindicated''', do not start<ref name="trulicity-label"/>

| counseling = * Use the pre-filled pen as directed; the needle is hidden — patients do not see it. This is often the preferred GLP-1 RA for needle-averse patients.{{Citation needed}}