Dulaglutide

At a Glance

Classification: Long-acting glucagon-like peptide-1 (GLP-1) receptor agonist; recombinant fusion protein of two GLP-1 analog chains linked to a modified human IgG4 Fc fragment; once-weekly incretin therapy

Dulaglutide is a once-weekly GLP-1 receptor agonist made by Eli Lilly and sold as Trulicity. It was approved by the FDA in 2014 for type 2 diabetes. It is built as a fusion protein: two modified GLP-1 peptides attached to part of an antibody (an IgG4 Fc fragment), which makes it last about a week in the body. Its human evidence is extensive: • The AWARD phase 3 program (head-to-head and placebo-controlled glucose trials) • The REWIND cardiovascular outcomes trial (about 9,900 people) • A trial in youths aged 10 to under 18. Its US label includes reducing the risk of major cardiovascular events in adults with type 2 diabetes who have established heart disease or multiple risk factors, and use in pediatric patients 10 years and older with type 2 diabetes. Dulaglutide is not approved for weight loss. Its label carries a boxed warning about thyroid C-cell tumors seen in rodents.

What Is Dulaglutide?

GLP-1 is a gut hormone released after meals. It increases glucose-dependent insulin release, lowers glucagon, slows stomach emptying and reduces appetite. Natural GLP-1 lasts only minutes. Liraglutide → fatty-acid-attached GLP-1 analog, once daily Semaglutide → fatty-acid-attached GLP-1 analog, once weekly (and oral) Dulaglutide → GLP-1 analog fused to an antibody Fc fragment, once weekly Tirzepatide → dual GIP/GLP-1 receptor agonist, once weekly All act on the GLP-1 receptor, but they are different molecules with different trial records.

What Are Researchers Studying?

How Does It Work?

Dulaglutide ↓ GLP-1 receptor (pancreatic beta cells, alpha cells, brain, gut) ↓ cAMP signaling ↓ more insulin when glucose is high, less glucagon, slower gastric emptying, reduced appetite ↓ lower HbA1c and modest weight loss. The Fc fusion makes the molecule too large to be filtered quickly by the kidneys and protects it from breakdown, giving a half-life of about five days and once-weekly dosing.

What Does the Research Show?

Notable Studies

What We Still Don't Know

• Long-term cardiovascular and safety outcomes at the higher 3.0 and 4.5 mg doses • How dulaglutide compares head-to-head on hard outcomes with semaglutide or tirzepatide • Effects in people without diabetes (no obesity indication) • Long-term outcomes of pediatric use • Human relevance of the rodent thyroid C-cell tumor findings

Related Compounds

Sources & References

1. Gerstein HC et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. The Lancet. 2019.
2. Dungan KM et al. Once-weekly dulaglutide versus once-daily liraglutide in metformin-treated patients with type 2 diabetes (AWARD-6): a randomised, open-label, phase 3, non-inferiority trial. The Lancet. 2014.
3. Frias JP et al. Efficacy and Safety of Dulaglutide 3.0 mg and 4.5 mg Versus Dulaglutide 1.5 mg in Metformin-Treated Patients With Type 2 Diabetes in a Randomized Controlled Trial (AWARD-11). Diabetes Care. 2021.
4. Arslanian SA et al. Once-Weekly Dulaglutide for the Treatment of Youths with Type 2 Diabetes. New England Journal of Medicine. 2022.
5. Umpierrez G, et al. Efficacy and safety of dulaglutide monotherapy versus metformin in type 2 diabetes in a randomized controlled trial (AWARD-3). Diabetes Care. 2014.