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 immunoglobulin G4 (IgG4) Fc fragment. This structure 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 receptor-mediated clearance, while the DPP-4-resistant GLP-1 sequence ensures sustained activity. **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 2–4 kg. Cardiovascular outcome trials (REWIND) showed a 12% reduction in major adverse cardiovascular events (MACE) in patients with or without established CVD. Safety profiles include mild-to-moderate gastrointestinal effects (nausea, diarrhea) and a low risk of hypoglycemia. Long-term data indicate potential benefits on renal outcomes and non-alcoholic steatohepatitis (NASH) biomarkers. **Clinical Relevance** Approved for type 2 diabetes (monotherapy or combination) and for reducing cardiovascular risk in adults with type 2 diabetes and established CVD or multiple risk factors. Dulaglutide is contraindicated in patients with medullary thyroid carcinoma or multiple endocrine neoplasia type 2. Its once-weekly dosing improves adherence, and its cardiovascular benefits position it as a preferred agent in high-risk populations. Ongoing research explores its role in obesity and neurodegenerative diseases. For research purposes only — not medical advice.

Key data

Category
Metabolic & Weight
Half-life
~5 days
Administration
subcutaneous
Research status
approved
References
1,278
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

Primary endpoint occurred in 12.2% of tirzepatide group vs 13.1% of dulaglutide group (HR 0.92; 95.3% CI 0.83–1.01; P=0.003 for noninferiority).; Superiority of tirzepatide was not established (P=0.09).; Adverse events were similar between groups, though more gastrointestinal events occurred with tirzepatide.

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

Switching to tirzepatide led to a significantly greater HbA1c reduction than escalating dulaglutide (estimated treatment difference -0.77%).; Weight loss was significantly greater with tirzepatide (-10.5 kg) versus dulaglutide (-3.6 kg).; Serious adverse event rates were similar between groups (7.2% tirzepatide vs 7.0% dulaglutide).; Most common adverse events were nausea and diarrhea in both groups.

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

GLP-1RAs (liraglutide and dulaglutide) reduce binge eating frequency and comorbidities.; GLP-1RAs have a favorable psychiatric side effect profile compared to current options.; Large-scale, blinded placebo-controlled trials are lacking.; Rigorous clinical trials are needed to establish efficacy, dosing, safety, and comparative effectiveness.

Effects of dulaglutide on alcohol consumption during smoking cessation
JCI insight · 2023 · PubMed

Participants receiving dulaglutide drank 29% less alcohol at week 12 than those on placebo (relative effect = 0.71, 95% CI 0.52-0.97, P = 0.04).; Changes in alcohol consumption were not correlated with smoking status at week 12.; The study included 151 participants who reported drinking at baseline and completed 12 weeks of treatment (76 dulaglutide, 75 placebo).; Results support the potential of GLP-1 agonists for treating substance use disorders.

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 at doses ≥12 mg produced statistically superior HbA1c reductions versus placebo (treatment difference -0.8% to -1.7%).; Maximum body weight loss with orforglipron was -10.1 kg (placebo-adjusted -7.9 kg), compared to -2.2 kg with placebo and -3.9 kg with dulaglutide.; Treatment-emergent adverse events occurred in 61.8% to 88.9% of orforglipron groups, mostly mild-to-moderate gastrointestinal events.; Clinically significant hypoglycemia occurred in 3 orforglipron participants and 1 dulaglutide participant; no severe hypoglycemia or treatment-related deaths were reported.

Weight-dependent and weight-independent effects of dulaglutide on blood pressure in patients with type 2 diabetes
Cardiovascular diabetology · 2023 · PubMed

Dulaglutide 1.5 mg reduced SBP by -2.6 mmHg (95% CI: -3.8, -1.5) after placebo adjustment, with 36% weight-dependent and 64% weight-independent effects.; Pulse pressure reduction was -2.5 mmHg (95% CI: -3.5, -1.5), with 14% weight-dependent and 86% weight-independent effects.; Dulaglutide had limited impact on diastolic blood pressure, with only a small weight-mediated effect.; Dulaglutide 4.5 mg showed additional SBP and pulse pressure reductions beyond 1.5 mg, primarily weight-mediated.

Metabolic remodeling of glycerophospholipids acts as a signature of dulaglutide and liraglutide treatment in recent-onset type 2 diabetes mellitus
Frontiers in endocrinology · 2023 · 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 immunoglobulin G4 (IgG4) Fc fragment. This structure extends its half-life to approximately 5 days, enabling once-weekly subcutaneous administration.

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 1,278 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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