# Dulaglutide

> Once-weekly GLP-1 receptor agonist built as an Fc-fusion protein (Trulicity) — FDA-approved for type 2 diabetes since 2014, with cardiovascular-outcomes data from REWIND.

- Also known as: Trulicity, LY2189265
- Class: Metabolic, Peptide Hormones
- FDA approved: Yes
- Canonical page: https://americanpeptide.com/catalog/dulaglutide

## Overview

Dulaglutide solves the half-life problem a different way from semaglutide. Instead of attaching a fatty acid to a synthetic peptide, it fuses two copies of a DPP-4-resistant GLP-1 analog to a modified human IgG4 Fc fragment, producing a ~59.7 kDa recombinant protein with a half-life of about five days. Eli Lilly’s Trulicity was approved by the FDA in September 2014 for type 2 diabetes; the REWIND trial (Lancet 2019) later showed a 12% reduction in major adverse cardiovascular events, extending the label to cardiovascular risk reduction.

Native GLP-1 lasts about two minutes in circulation — cleaved by DPP-4 and cleared by the kidney. The incretin field found three engineering answers. Liraglutide and semaglutide attach a fatty acid so the peptide rides on albumin. Albiglutide fused GLP-1 to albumin directly. Dulaglutide fuses it to an antibody fragment: each of its two identical chains is a GLP-1(7–37) analog with substitutions that block DPP-4 cleavage, joined by a short peptide linker to a modified IgG4 Fc domain engineered to minimize immune effector function.

That makes it a biologic rather than a synthetic peptide — expressed in mammalian cell culture, glycosylated, and far too large for solid-phase synthesis. The AWARD Phase 3 program established its glycemic efficacy at 0.75 mg and 1.5 mg weekly, and AWARD-11 added 3.0 mg and 4.5 mg doses (approved 2020). Weight loss is modest by current standards — a few kilograms on average — which is why it is positioned as a diabetes drug and has no obesity indication.

Its landmark is REWIND (Gerstein et al., Lancet 2019): 9,901 adults with type 2 diabetes followed for a median 5.4 years, most of them without established cardiovascular disease. Dulaglutide reduced major adverse cardiovascular events by 12% (hazard ratio 0.88, 95% CI 0.79–0.99), supporting an indication that covers primary as well as secondary prevention. It is also approved for type 2 diabetes in patients aged 10 and older. Dulaglutide now serves as the active comparator the newer agents are measured against — including tirzepatide’s cardiovascular-outcomes trial, SURPASS-CVOT.

## Mechanism

GLP-1 receptor agonism → glucose-dependent insulin secretion, glucagon suppression, slowed gastric emptying and reduced appetite. The Fc domain enlarges the molecule beyond renal filtration and recycles it through the neonatal Fc receptor, extending exposure to once-weekly.

## Chemistry

| Property | Value |
| --- | --- |
| Molecular weight | 59700 Da |
| CAS number | 923950-08-7 |

## Research areas

Studied in: Type 2 diabetes, Cardiovascular risk reduction, Pediatric type 2 diabetes, Obesity.

Guides on this site:

- [Weight Loss & Metabolic Health](https://americanpeptide.com/research-areas/weight-loss): Incretin and metabolic peptides studied for glycemic control and fat loss.

## Key research

- Fc-fusion half-life extension — two GLP-1 analog chains fused to a modified IgG4 Fc; ~59.7 kDa, half-life ~5 days, once-weekly dosing.
- Cardiovascular outcomes — REWIND (Lancet 2019, n=9,901, median 5.4 years) reported a 12% MACE reduction (HR 0.88), largely in a primary-prevention population.
- Glycemic control — the AWARD program supports doses from 0.75 mg to 4.5 mg weekly in type 2 diabetes.
- Pediatric use — approved for type 2 diabetes from age 10 (AWARD-PEDS).
- Benchmark comparator — the reference arm in later incretin trials, including tirzepatide’s SURPASS-CVOT.

## Storage, handling & synthesis

**Storage.** Supplied as a ready-to-use solution in a single-dose pen, stored refrigerated at 2–8 °C and protected from light; do not freeze.

**Handling.** A glycosylated fusion protein, not a lyophilized peptide — there is no reconstitution step. Sensitive to freezing, heat and agitation, which can cause aggregation.

## FAQs

### What is dulaglutide?

Dulaglutide (Trulicity) is a once-weekly GLP-1 receptor agonist from Eli Lilly, FDA-approved since 2014 for type 2 diabetes and for reducing cardiovascular risk in adults with type 2 diabetes.

### How is dulaglutide different from semaglutide?

Both are once-weekly GLP-1 agonists, but they are built differently. Semaglutide is a ~4.1 kDa synthetic peptide carrying a fatty-acid chain that binds albumin. Dulaglutide is a ~59.7 kDa recombinant protein — two GLP-1 analog chains fused to an antibody Fc fragment. Semaglutide produces substantially more weight loss and has an obesity indication; dulaglutide does not.

### Is dulaglutide a peptide?

It is a fusion protein rather than a synthetic peptide: the GLP-1-like portion is a peptide sequence, but it is expressed as part of a larger Fc-fusion in mammalian cells and cannot be made by solid-phase synthesis.

### Does dulaglutide cause weight loss?

Modestly — trials report average losses of a few kilograms, increasing with dose. It is not approved for weight management.

### What did the REWIND trial show?

In 9,901 adults with type 2 diabetes followed for a median 5.4 years, dulaglutide reduced major adverse cardiovascular events by 12% versus placebo (HR 0.88, 95% CI 0.79–0.99). Most participants had risk factors rather than established cardiovascular disease.

### What are the side effects of dulaglutide?

Mainly gastrointestinal — nausea, diarrhea, vomiting and reduced appetite. The label carries the class boxed warning about thyroid C-cell tumors seen in rodent studies. This page is a research reference, not medical advice.

## Latest research

Recent trials and publications mentioning Dulaglutide, pulled automatically from ClinicalTrials.gov and PubMed (unfiltered search results, refreshed daily).

### Recent trials

- [24-hour Clear Liquid Diet vs. Standard Fasting for Upper Gastrointestinal Endoscopy in Patients Taking Agonists of the GLP-1 Receptor](https://clinicaltrials.gov/study/NCT07929233) — NOT_YET_RECRUITING · NA · NCT07929233
- [A Study of Orforglipron (LY3502970) Compared With Dulaglutide in Pediatric Participants With Type 2 Diabetes](https://clinicaltrials.gov/study/NCT07668336) — RECRUITING · PHASE3 · NCT07668336
- [A Real-world Study of Treatment Retention and Adherence to Secukinumab in Patients With Plaque Psoriasis (PsO) With or Without Glucagon-like Peptide-1 Receptor Agonist (GLP-1 RA) Co-therapy](https://clinicaltrials.gov/study/NCT07881783) — NOT_YET_RECRUITING · NCT07881783
- [Therapeutic Strategies for Microvascular Dysfunction in Type 1 Diabetes](https://clinicaltrials.gov/study/NCT05478707) — RECRUITING · PHASE2 · NCT05478707
- [Effect of Weekly GLP1 Agonist Treatment in "Double Diabetes"](https://clinicaltrials.gov/study/NCT05305794) — RECRUITING · PHASE3 · NCT05305794
- [Weekly GLP-1 Receptor Agonists in Obese Individuals Without Diabetes](https://clinicaltrials.gov/study/NCT07834398) — COMPLETED · PHASE3 · NCT07834398

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Source: AmericanPeptide.com — https://americanpeptide.com/catalog/dulaglutide
Data license: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Attribution: AmericanPeptide.com.
Research reference only — computational and educational content, not medical advice.