Dulaglutide
Dulaglutide, a peptide. Modified GLP-1(7-37) analog fused via a small linker to a human IgG4 Fc fragment (C-terminus to N-terminus of Fc).… Subcutaneous half-life 5 d.
Modified GLP-1(7-37) analog fused via a small linker to a human IgG4 Fc fragment (C-terminus to N-terminus of Fc). Aib at position 8 blocks DPP-4 cleavage; four Gly-Gly-Gly-Gly-Ser linker repeats precede the Fc. Large MW (~63 kDa) + FcRn-mediated recycling extend plasma t½ to ~4.7 days — enabling once-weekly SC dosing. Activates GLP-1R at β-cells (insulin release), α-cells (glucagon suppression), hypothalamus (satiety), and gut (gastric emptying). REWIND trial: 12% MACE reduction in T2D with CV risk.
PK: Geiser 2016 (PMID:26507721), pooled population analysis in type 2 diabetes, verbatim "had a terminal elimination half-life of 5 days" = 120 h; the stored 113 h appears nowhere. Corroborated by Xu 2022 (PMID:34787823), "half-life of 4-5 days". V 21 L, F 0.55 and ka 0.02 /h dropped 2026-09-06: the cited abstract states none of them, and the approval document gives apparent volumes of 3.09 L central plus 5.98 L peripheral, roughly 9 L in total rather than 21. Bioavailability is also dose-dependent there — 65% at 0.75 mg against 47% at 1.5 mg — so a single scalar F is structurally wrong for this drug. PK: ABSORPTION RATE AUTHORED FROM A VERBATIM PEAK TIME. This row carried no ka, so the solver substituted 1.0/h and the modelled peak landed at 5.2 h — for a slowly-absorbed subcutaneous product that is wrong by design, not by a little. Source: "median time to Cmax (tmax) of approximately 48 h", single dose in healthy subjects. With the stored half-life fixing ke, Tmax solves uniquely for ka by inverting the model own definition, ln(ka/ke)/(ka-ke) = Tmax — ARITHMETIC, NOT AN ESTIMATE — giving 0.05126/h, which reproduces 48 h on substitution. EXPOSURE IS UNCHANGED: the absorption rate cancels out of AUC entirely, so only the shape moves.
Pharmacokinetics
- Subcutaneous — t½ 5.0 d · ka 0.05126 h⁻¹
Sources: PMID:26507721, PMID:34787823