Overview
Dulaglutide is a once-weekly injectable GLP-1 receptor agonist developed by Eli Lilly and FDA-approved in 2014. Structurally, it consists of two GLP-1 analog chains covalently linked to a modified human IgG4 Fc fragment, enabling its extended half-life. The REWIND cardiovascular outcomes trial established dulaglutide as one of the few GLP-1 agents with demonstrated reduction in major adverse cardiovascular events.
Mechanism of action
Dulaglutide activates GLP-1 receptors on pancreatic beta cells in a glucose-dependent manner, stimulating insulin secretion via cAMP/PKA signaling while suppressing glucagon release from alpha cells. The fusion to IgG4 Fc dramatically extends the half-life to approximately 90 hours by reducing renal clearance and conferring resistance to DPP-4 degradation. Gastric emptying is slowed, reducing postprandial glucose excursions. Central GLP-1R signaling in the hypothalamus and area postrema suppresses appetite and promotes satiety. The Fc domain also prevents neonatal Fc receptor (FcRn)-mediated degradation, enabling once-weekly subcutaneous dosing with stable plasma concentrations.
Dosing protocols
| Purpose | Route | Dosage | Frequency | Notes |
|---|---|---|---|---|
| type 2 diabetes glycemic control | subcutaneous | 0.75–1.5 mg | once weekly | Start at 0.75 mg once weekly. May increase to 1.5 mg once weekly for additional glycemic control after at least 4 weeks. Some patients titrate to 3 mg or 4.5 mg (higher approved doses). |
| cardiovascular risk reduction | subcutaneous | 0.75–1.5 mg | once weekly | Same dosing as glycemic control. REWIND trial used 1.5 mg/week. Inject on same day each week regardless of meals. |
Dosing information is for educational purposes only. Consult a qualified healthcare professional before using any peptide.
Research summary
The AWARD phase 3 program across 8 trials demonstrated HbA1c reductions of 0.7–1.6% and weight loss of 1.5–3.0 kg vs. placebo. The landmark REWIND trial (9,901 patients, median 5.4 years follow-up) showed a 12% reduction in major adverse cardiovascular events (MACE: CV death, nonfatal MI, nonfatal stroke) vs. placebo in patients with established or high CV risk. This MACE benefit was observed even in patients without prior cardiovascular disease at baseline — a distinguishing feature among GLP-1 agents.
Side effects
Side effects vary by individual. This is not an exhaustive list. Report unusual symptoms to a healthcare professional.
Common stacks
Peptides commonly paired with Dulaglutide for synergistic effects.
Legal status
FDA-approved September 2014. Indicated for type 2 diabetes mellitus glycemic control and cardiovascular risk reduction in adults with established cardiovascular disease or multiple CV risk factors. Available as prefilled auto-injector pen. Patent protection ongoing; biosimilar entry expected mid-2020s.
Where to get it
Prescription required
Dulaglutide is a prescription medication. Consult your healthcare provider or a licensed telehealth platform for access.