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GLP-1 built as an antibody fragment: at about 59,700 Da it is the largest molecule in the incretin class, dosed once a week without any lipid.
Also known as: Trulicity · LY2189265
Part of the Metabolic & GLP-1 peptides cluster
Overview
Dulaglutide (Trulicity) is a once-weekly GLP-1 receptor agonist built as a fusion protein: two DPP-4-resistant GLP-1 analogue chains linked to a modified human IgG4 Fc fragment, with a molecular weight of about 59,669 Da. It is approved for type 2 diabetes in adults and in youths aged 10 and over, and it is the active comparator against which tirzepatide (SURPASS-CVOT, SURPASS-SWITCH), semaglutide (SUSTAIN 7) and orforglipron were tested.
Source & context
Biological / chemical source: Recombinant GLP-1 analog fused to a human IgG4 Fc fragment
Primary research or clinical context: Approved for type 2 diabetes in adults (Canada, US, EU) and — since 2022 trial data — in youths aged 10 and over; the most-used comparator in the tirzepatide and orforglipron programmes
What dulaglutide is
Dulaglutide is a GLP-1 receptor agonist that reaches once-weekly dosing by a different route from every other molecule in the class: instead of a fatty acid that binds albumin, it fuses two GLP-1 analogue chains to a modified human IgG4 Fc fragment, producing a 59,669-dalton protein that is too large for the kidney to filter and is recycled like an antibody (LactMed 2026; IUPHAR). IUPHAR describes it as a GLP-1 mimetic whose in-vivo immunoreactivity remains detectable for more than six days after administration, hence weekly injection. It is marketed by Eli Lilly as Trulicity.
Structure: peptide or protein?
Strictly, dulaglutide is a recombinant protein containing peptide hormone analogues. The GLP-1 portions are modified to resist DPP-4 cleavage, and the Fc portion is engineered to reduce immune effector activity; the whole assembly is produced in mammalian cells rather than by chemical synthesis. That is why this profile carries no one-letter sequence chips and why the pipeline could not resolve a PubChem entry for it — it is beyond the size and complexity that small-molecule registries cover. In the half-life comparison guide it is the example of the Fc-fusion strategy, alongside the lipidation strategy of semaglutide and tirzepatide.
Mechanism
The GLP-1 chains activate the GLP-1 receptor exactly as the native hormone does: glucose-dependent insulin secretion, glucagon suppression, slower gastric emptying and reduced appetite. Dulaglutide is a single-receptor agonist and does not act at the GIP or glucagon receptors, which is the mechanistic reason the dual agonist tirzepatide out-performs it head-to-head. Because it is dosed as a fixed protein rather than a titratable small peptide, its labelled doses run from 0.75 mg to 4.5 mg weekly.
Head-to-head evidence
Dulaglutide is the comparator of record for the newer incretins. In SUSTAIN 7 (Pratley et al., Lancet Diabetes & Endocrinology 2018), 1,201 patients with type 2 diabetes were randomised to semaglutide or dulaglutide once weekly. In SURPASS-SWITCH (Billings et al., Annals of Internal Medicine 2025), 282 adults inadequately controlled on lower-dose dulaglutide were randomised to switch to tirzepatide or escalate dulaglutide: at 40 weeks HbA1c fell 1.44 points with tirzepatide versus 0.67 with dulaglutide 4.5 mg, and weight fell 10.5 kg versus 3.6 kg, with serious adverse events in about 7% of each group. SURPASS-CVOT (Nicholls et al., NEJM 2025) randomised 13,299 patients with type 2 diabetes and cardiovascular disease to tirzepatide or dulaglutide for cardiovascular outcomes. Orforglipron's phase 2 also used dulaglutide as the active comparator (Frias et al., Lancet 2023).
| Trial | Versus | Population | Key result |
|---|---|---|---|
| SUSTAIN 7 (2018) | Semaglutide | 1,201 adults, T2D | Semaglutide vs dulaglutide once weekly, phase 3b |
| SURPASS-SWITCH (2025) | Tirzepatide | 282 adults, T2D on dulaglutide | HbA1c −1.44 vs −0.67 pts; weight −10.5 vs −3.6 kg at 40 wk |
| SURPASS-CVOT (2025) | Tirzepatide | 13,299 adults, T2D + CVD | Cardiovascular outcomes; mean age 64, HbA1c 8.4% |
| Orforglipron phase 2 (2023) | Orforglipron | Adults, T2D | Dulaglutide as active control |
Paediatric approval and safety
In a 26-week randomised trial of 154 youths with type 2 diabetes, HbA1c rose 0.6 points on placebo and fell 0.6 and 0.9 points on dulaglutide 0.75 mg and 1.5 mg respectively, with a higher proportion reaching an HbA1c below 7% (Arslanian et al., NEJM 2022) — the basis of the paediatric indication. A 2026 cohort study of over 130,000 matched pairs found the hazard of gastrointestinal events with semaglutide or tirzepatide versus dulaglutide to be close to 1.0, i.e. the three drugs have similar gastrointestinal safety (Crisafulli et al., Annals of Internal Medicine 2026). Dulaglutide has also been tested for alcohol consumption during smoking cessation (Probst et al., JCI Insight 2023).
Dulaglutide vs semaglutide vs tirzepatide
All three are once-weekly incretin injections approved for type 2 diabetes. Semaglutide and tirzepatide are lipidated peptides (about 4–5 kDa); dulaglutide is an Fc-fusion protein (about 60 kDa). In head-to-head trials, tirzepatide produced larger HbA1c and weight reductions than dulaglutide, and gastrointestinal safety across the three appears similar in real-world data. Dulaglutide has no obesity indication; its role is glycaemic control, where its fixed-dose weekly pen and long safety record keep it in wide use. This profile is educational; it is not guidance on obtaining or using any product and it is not medical advice.
Structure & chemistry
Molecular identity & reference confidence
Reference mass unavailable
Reference values are taken from the cited molecular record or curated profile. A database match is not independent laboratory verification; modifications, counter-ions, and formulations can change the measured mass.
- Molecular form
- Two GLP-1 analogue chains covalently linked to a modified human IgG4 Fc fragment; a recombinant protein, not a synthetic peptide
- Species
- Not established by this molecular identity audit
- Termini (N / C)
- Not specified / Not specified
Average reference mass
Reference policy updated: 2026-10-05
- IUPHAR/BPS source snapshot · 2026-09-06
- Plasma half-life
- Immunoreactivity detectable for more than 6 days after a dose (IUPHAR); supports once-weekly administration
- Receptors
- GLP-1 receptor (GLP-1R)
- Backbone
- Two GLP-1 analogue chains covalently linked to a modified human IgG4 Fc fragment; a recombinant protein, not a synthetic peptide
- Status
- Approved (Trulicity): type 2 diabetes in adults and, following the 2022 AWARD-PEDS trial, youths aged 10+
- IUPHAR ligand: 7638
- CAS RN: 923950-08-7
Chemistry values: curated profile, IUPHAR/BPS Guide to Pharmacology · fetched 2026-09-06.
Clinical development snapshot
ClinicalTrials.gov lists 142 registered studies with “Dulaglutide” as an intervention (snapshot 2026-10-01). A registry footprint is not evidence of efficacy or approval.
| NCT | Title | Phase | Status | Updated |
|---|---|---|---|---|
| NCT07668336 | A Study of Orforglipron (LY3502970) Compared With Dulaglutide in Pediatric Participants With Type 2 Diabetes | Phase 3 | not yet recruiting | 2026-09-25 |
| NCT07834398 | Weekly GLP-1 Receptor Agonists in Obese Individuals Without Diabetes | Phase 3 | completed | 2026-09-22 |
| NCT06779929 | Comparative Study of Tirzepatide Versus Dulaglutide (SURPASS CVOT) or Semaglutide on Major Cardiovascular Even | — | completed | 2026-09-18 |
| NCT07820111 | Comparative Study of Different Weekly GLP-1 Receptor Agonists Among Diabetic and Non-Diabetic Patients: Clinic | Phase 3 | completed | 2026-09-15 |
| NCT06851962 | Impact of Pharmacogenetic-Guided Treatment on Type 2 Diabetes. | Phase 4 | completed | 2026-09-04 |
| NCT07787936 | GLP-1/GIP Receptor Agonists in Obesity-Related HFpEF: The GLIDE-HF Registry | — | not yet recruiting | 2026-08-26 |
Change log
Dated observations from the data pipeline (registry flags, trial footprints, identifiers) and editorial reviews of this profile.
- Trials2 registered studies added on ClinicalTrials.gov (now 142).
- EditorialProfile content reviewed and updated by the editorial team.
FAQ about Dulaglutide
What is Dulaglutide?+
Dulaglutide (Trulicity) is a once-weekly GLP-1 receptor agonist built as a fusion protein: two DPP-4-resistant GLP-1 analogue chains linked to a modified human IgG4 Fc fragment, with a molecular weight of about 59,669 Da. It is approved for type 2 diabetes in adults and in youths aged 10 and over, and it is the active comparator against which tirzepatide (SURPASS-CVOT, SURPASS-SWITCH), semaglutide (SUSTAIN 7) and orforglipron were tested.
What Canadian product status is recorded for Dulaglutide?+
Canadian product status for Dulaglutide has not been verified in this profile. No verified record here does not mean no authorization exists. Status depends on the product, formulation and use; consult Health Canada's product records.
What is the typical length of Dulaglutide?+
Dulaglutide is not a classic amino-acid chain peptide in the same sense; see the profile for classification details.
Is dulaglutide a peptide?+
It is a fusion protein: two GLP-1 peptide analogues joined to an IgG4 Fc fragment, about 59,669 Da. It behaves pharmacologically as a GLP-1 receptor agonist.
What is dulaglutide's half-life?+
IUPHAR records immunoreactivity detectable for more than six days after a dose, which supports once-weekly dosing.
Dulaglutide vs tirzepatide — which lowered HbA1c more?+
Tirzepatide: in SURPASS-SWITCH, −1.44 points versus −0.67 with dulaglutide 4.5 mg at 40 weeks, and −10.5 kg versus −3.6 kg in weight.
Is dulaglutide approved for children?+
For youths aged 10 and over with type 2 diabetes, following the 2022 trial in 154 participants.
Is dulaglutide approved for weight loss?+
No. Its indication is type 2 diabetes; the obesity indications belong to semaglutide and tirzepatide.
Does dulaglutide have more gastrointestinal side effects than semaglutide?+
A 2026 matched cohort study found similar rates of gastrointestinal events across dulaglutide, semaglutide and tirzepatide.
Further reading
- Metabolic peptidesGLP-1 Peptides Explained: GLP-1, Semaglutide, Tirzepatide, RetatrutideFrom endogenous GLP-1 to dual and triple agonists—an educational map of incretin peptide science and metabolic drug design.
- PharmacologyGLP-1 and Incretin Peptide Half-Lives Compared: From 2 Minutes to 8 DaysA sourced table of the plasma half-lives of native GLP-1, exenatide, liraglutide, dulaglutide, semaglutide, tirzepatide, retatrutide, cagrilintide and the newer co-agonists — and the three engineering strategies (DPP-4 resistance, albumin binding, Fc fusion) that stretch minutes into a week.
- ComparisonSemaglutide vs Tirzepatide: Structure, Receptors, Half-Life and the SURMOUNT-5 Head-to-HeadA mechanistic comparison of semaglutide (single GLP-1 agonist) and tirzepatide (dual GIP/GLP-1 agonist): sequences, side chains, half-lives, and what the only head-to-head trial, SURMOUNT-5, actually showed.
- ComparisonOrforglipron vs Peptide GLP-1 Agonists: Small Molecule vs Peptide, ExplainedOrforglipron (Foundayo, FDA-approved in the US in April 2026) is the first non-peptide GLP-1 receptor agonist. This guide explains how a small molecule activates a peptide receptor, why that allows a pill without food or water restrictions, how ATTAIN-1 results compare with semaglutide and tirzepatide trials, and what the trade-offs are.
Related peptides
References & further reading
- 1.Nicholls et al. (2025). Cardiovascular Outcomes with Tirzepatide versus Dulaglutide in Type 2 Diabetes. N Engl J Med
- 2.Pratley et al. (2018). Semaglutide versus dulaglutide once weekly in patients with type 2 diabetes (SUSTAIN 7): a randomised, open-label, phase 3b trial. Lancet Diabetes Endocrinol
- 3.Karimi et al. (2025). Comparative effectiveness of semaglutide versus liraglutide, dulaglutide or tirzepatide: a systematic review and meta-analysis. Front Pharmacol
- 4.Inagaki et al. (2022). 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. Lancet Diabetes Endocrinol
- 5.Billings et al. (2025). 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. Ann Intern Med
- 6.Takahashi et al. (2023). Improvement of glycaemic control and treatment satisfaction by switching from liraglutide or dulaglutide to subcutaneous semaglutide in patients with type 2 diabetes: A multicentre, prospective, randomized, open-label, parallel-group comparison study (SWITCH-SEMA 1 study). Diabetes Obes Metab
- 7.Arslanian et al. (2022). Once-Weekly Dulaglutide for the Treatment of Youths with Type 2 Diabetes. N Engl J Med
- 8.Guo et al. (2026). Mazdutide versus dulaglutide in Chinese adults with type 2 diabetes. Nature
- 9.Frias JP et al. (2018). Efficacy and safety of LY3298176, a novel dual GIP and GLP-1 receptor agonist, in patients with type 2 diabetes. Lancet
- 10.Frias JP et al. (2023). Efficacy and safety of oral orforglipron in patients with type 2 diabetes: phase 2 study. Lancet
- 11.Crisafulli S et al. (2026). Comparative gastrointestinal safety of dulaglutide, semaglutide, and tirzepatide in adults with type 2 diabetes. Annals of Internal Medicine
- 12.LactMed (2026). Dulaglutide. Drugs and Lactation Database, NICHD