Dulaglutide

Dulaglutide (LY-2189265) is a novel, long-acting glucagon-like peptide 1 (GLP-1) analog for the treatment of type 2 diabetes mellitus (T2DM) ^[1].

Dulaglutide (LY2189265) significantly decreased hepatic lipid accumulation and reduced the expression of genes associated with lipid droplet binding proteins, de novo lipogenesis, and TG synthesis in PA-treated HepG2 cells. Dulaglutide (LY2189265) also increased the expression of proteins associated with lipolysis and fatty acid oxidation and FAM3A in PA-treated cells^[8].Dulaglutide (LY2189265) significantly promoted microglia to phagocytose and get rid of the Aβ plague. Additionally, Dulaglutide (LY2189265) treatment inhibited the production of pro-inflammatory factors, including tumor necrosis factor (TNF)-α, interleukin -1β, and IL-6, whereas increased the load of anti-inflammatory molecules such as IL-10 affected by Aβ1-42 exposure^[9].

Dulaglutide (LY2189265) administration attenuated muscle wasting and restored muscle strength by reducing inflammation through the OPA-1-TLR-9 signaling pathway in the tibialis anterior (TA) and quadriceps (QD) muscles of aged mice^[3]. Dulaglutide (LY2189265) may reduce the hyperandrogenemia of PCOS rats by regulating the content of serum SHBG and the expression of 3βHSD, CYP19α1, and StAR related genes and proteins, thereby inhibiting the excessive development of small follicles and the formation of cystic follicles in the ovaries of PCOS rats, thereby improving polycystic ovary in PCOS rats^[4]. Dulaglutide (LY2189265) improves learning and memory ability in 9-week-old male wild-type C57/BL6 mice (AD mice)^[2].

After subcutaneous injection, Dulaglutide (LY2189265) was slowly absorbed and tmax at steady state ranged from 24 to 72 h (median = 48 h) ^[5，6]. The absolute bioavailability was 47% and the half-life was estimated at 4.7 days. Steady state was achieved between 2 and 4 weeks of dosing and the accumulation ratio was approximately 1.56^[7].