Dulaglutide: Weekly GLP-1 for Type 2 Diabetes (Trulicity)
GLP-1 agonist fused to an IgG4-Fc fragment. Once-weekly, FDA-approved for T2D and CV risk reduction.
✅ Approved
- Full name
- Dulaglutide
- Class
- GLP-1 receptor agonist (Fc-fusion)
- Half-life
- ~5 days
- Route
- Subcutaneous weekly
- Brand names
- Trulicity (Eli Lilly)
- Regulatory status
- FDA-approved 2014 (T2D), 2020 (CV risk reduction)
What it is
Dulaglutide is a recombinant fusion protein of two modified GLP-1 analogue peptides linked to a human IgG4-Fc fragment. The Fc component confers long half-life via FcRn recycling, enabling once-weekly dosing. Unlike semaglutide, it is not approved for obesity alone and produces smaller weight loss (~3 kg).
How it works
The GLP-1 arms activate β-cell receptors to drive glucose-dependent insulin secretion and suppress glucagon. Gastric-emptying and satiety effects are modest compared with semaglutide.
The IgG4-Fc design avoids CYP metabolism and renal clearance issues and produces a flat PK profile, but limits CNS penetration relative to albumin-bound analogues — partially explaining weaker weight effects.
What the research shows
The AWARD and REWIND programmes established efficacy in T2D and cardiovascular benefit.
Gerstein HC et al. (2019) — REWIND: CV outcomes in T2D
Gerstein H.C. et al., Lancet 2019;394:121–130. 👥 Human studies
9,901 T2D patients (50% without established CV disease) randomised to dulaglutide 1.5 mg weekly or placebo, median follow-up 5.4 years.
MACE reduced 12% (HR 0.88, p=0.026). Benefit in primary as well as secondary prevention — unusual for incretin trials.
Limitations: Modest absolute risk reduction; GI side effects 47%.
Frias JP et al. (2018) — AWARD-11: higher doses
Frias J.P. et al., Diabetes Care 2021;44:765–773. 👥 Human studies
1,842 T2D patients tested dulaglutide 3.0 and 4.5 mg vs 1.5 mg.
Higher doses produced additional HbA1c and weight reductions (−4.6 kg at 4.5 mg vs −3.0 kg at 1.5 mg).
Limitations: Still inferior to semaglutide 2.4 mg for weight endpoints.
Safety and limitations
GI effects (nausea 29%, diarrhoea 13%, vomiting 10%) common. Class risks: pancreatitis, gallbladder disease, rodent C-cell tumour warning. Renal safety favourable due to Fc-mediated clearance.
Injection-site reactions occasionally linked to anti-drug antibodies against the Fc portion; clinically mild.