Dulaglutide

approved

Also known as: Trulicity, LY2189265

**Mechanism of Action** Dulaglutide is a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist engineered by fusing two GLP-1 analog molecules to a modified human IgG4 Fc fragment. This design extends its half-life to approximately 5 days, enabling once-weekly subcutaneous administration. It activates GLP-1 receptors in pancreatic β-cells, enhancing glucose-dependent insulin secretion, suppressing glucagon release, and slowing gastric emptying. The IgG4 Fc domain reduces immunogenicity and renal clearance, while the DPP-4-resistant GLP-1 sequence ensures sustained receptor activation. **Key Research Findings** Clinical trials (e.g., AWARD series) demonstrate that dulaglutide significantly reduces HbA1c (by 1.0–1.5%) and fasting plasma glucose in type 2 diabetes, with weight loss of 2–3 kg. Cardiovascular outcome trials (REWIND) show a 12% reduction in major adverse cardiovascular events (MACE) in patients with or without established CVD. Comparative studies indicate non-inferiority or superiority to liraglutide and sitagliptin in glycemic control, with a lower risk of hypoglycemia than sulfonylureas. Gastrointestinal adverse events (nausea, vomiting) are common but transient. **Clinical Relevance** Approved for type 2 diabetes as monotherapy or add-on to metformin, sulfonylureas, or insulin, dulaglutide is also indicated for cardiovascular risk reduction in adults with type 2 diabetes and established CVD or multiple risk factors. Its once-weekly dosing improves adherence. Contraindications include personal/family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2. Ongoing research explores potential benefits in obesity and non-alcoholic steatohepatitis (NASH). For research purposes only — not medical advice.

Key data

Category
Metabolic & Weight
Half-life
~5 days
Administration
subcutaneous
Research status
approved
References
1,219
Tags
glp-1, approved

Research & studies

Dulaglutide
2026 · PubMed
Cardiovascular Outcomes with Tirzepatide versus Dulaglutide in Type 2 Diabetes
The New England journal of medicine · 2025 · PubMed

Tirzepatide was noninferior to dulaglutide for cardiovascular outcomes (HR 0.92; 95.3% CI 0.83–1.01).; Superiority of tirzepatide was not demonstrated (P=0.09).; Gastrointestinal adverse events were more common with tirzepatide.; Overall adverse event incidence was similar between groups.

Comparison of Dose Escalation Versus Switching to Tirzepatide Among People With Type 2 Diabetes Inadequately Controlled on Lower Doses of Dulaglutide : A Randomized Clinical Trial
Annals of internal medicine · 2025 · PubMed
GLP-1 receptor agonists: A novel pharmacotherapy for binge eating (Binge eating disorder and bulimia nervosa)? A systematic review
Journal of clinical & translational endocrinology · 2024 · PubMed
Effects of dulaglutide on alcohol consumption during smoking cessation
JCI insight · 2023 · PubMed
Efficacy and safety of oral orforglipron in patients with type 2 diabetes: a multicentre, randomised, dose-response, phase 2 study
Lancet (London, England) · 2023 · PubMed

Orforglipron reduced HbA1c by up to -2.10% at week 26, versus -0.43% with placebo and -1.10% with dulaglutide.; Bodyweight reduction with orforglipron was up to -10.1 kg, compared with -2.2 kg for placebo and -3.9 kg for dulaglutide.; Treatment-emergent adverse events occurred in 61.8% to 88.9% of orforglipron participants, mostly mild-to-moderate gastrointestinal events.; Clinically significant hypoglycemia occurred in three orforglipron participants and one dulaglutide participant; no severe hypoglycemia was reported.

Efficacy and safety of tirzepatide monotherapy compared with dulaglutide in Japanese patients with type 2 diabetes (SURPASS J-mono): a double-blind, multicentre, randomised, phase 3 trial
The lancet. Diabetes & endocrinology · 2022 · PubMed
Transitioning to active-controlled trials to evaluate cardiovascular safety and efficacy of medications for type 2 diabetes
Cardiovascular diabetology · 2022 · PubMed

Frequently asked questions

What is Dulaglutide?

**Mechanism of Action** Dulaglutide is a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist engineered by fusing two GLP-1 analog molecules to a modified human IgG4 Fc fragment. This design extends its half-life to approximately 5 days, enabling once-weekly subcutaneous administration. It activates GLP-1 rece

How does Dulaglutide work?

Once-weekly GLP-1 receptor agonist fused to an IgG4 Fc fragment for extended half-life.

What is the research status of Dulaglutide?

Dulaglutide is currently classified as approved, with 1,219 research references on record. This is for research purposes only and is not medical advice.

What is the half-life of Dulaglutide?

The reported half-life of Dulaglutide is ~5 days.

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