Dulaglutide

Trulicity, LY2189265

Metabolic & weight

Awaiting medical reviewEN ES DE FR PT ZH+ Follow for updates

Note on this profile. Dulaglutide is an approved prescription medicine for type 2 diabetes, not a research-only compound. This page explains the published science. Use outside a prescription — it is not approved for weight loss — carries real risks discussed below.

Summary

Class: GLP-1 receptor agonist; a fusion protein in which two modified GLP-1 analogues are linked to a modified human IgG4 antibody fragment (Fc). Much larger than other GLP-1 drugs (~60 kDa)
Mechanism: Activates the GLP-1 receptor: glucose-dependent insulin release, lower glucagon, slower gastric emptying, reduced appetite; the antibody fragment keeps it in the blood for days
Routes studied: Subcutaneous once weekly (abdomen, thigh or upper arm)
Dose range reported: Approved: 0.75 mg once weekly, increasing to 1.5 mg; may be increased in steps after ≥4 weeks to 3 mg and then 4.5 mg weekly for additional glucose control. Paediatric (10+): 0.75 mg, may increase to 1.5 mg
Half-life: ~5 days (~120 hours); steady state after 2–4 weeks
Storage: Refrigerate (2–8 °C); may be kept at room temperature (up to 30 °C) for a total of 14 days. Do not freeze. Protect from light
Regulatory status: Approved medicine for type 2 diabetes in adults and children aged 10+ (US, EU, UK, AU, ZA and others)

Doses are as reported in studies or by the community — never recommendations.

1What it is

Dulaglutide is Eli Lilly's once-weekly GLP-1 receptor , approved in the US and EU in 2014 and sold as Trulicity. Its design is different from semaglutide or liraglutide. Instead of adding a fatty-acid chain to make the peptide stick to albumin, Lilly fused two copies of a modified GLP-1 sequence onto the "tail" (Fc region) of a human IgG4 antibody. The antibody fragment is too large to be filtered by the kidneys and is recycled by the body's own antibody-salvage system, giving a of about five days. The GLP-1 portion is modified to resist the DPP-4 enzyme, and the Fc portion is engineered to avoid triggering immune cell activation.

It was the best-selling GLP-1 medicine globally for several years before semaglutide and tirzepatide overtook it. It produces less weight loss than those two and is approved for glucose control and cardiovascular risk reduction, not for weight management.

2How it's thought to work

Dulaglutide's mechanism is the standard GLP-1 receptor profile:

Pancreas. increases glucose-dependent insulin secretion, restores some first-phase insulin response and suppresses inappropriately high glucagon.

Stomach. slows gastric emptying, mostly early in treatment; the effect fades with continued weekly exposure (tachyphylaxis), which is one reason the weight effect is modest.

Brain. reduces appetite and food intake via central GLP-1 receptors, although the large fusion protein is thought to reach brain appetite centres less readily than smaller analogues — a possible explanation for smaller weight loss.

Cardiovascular. the REWIND trial's benefit is attributed to effects on blood pressure, lipids, weight, inflammation and vascular biology rather than glucose alone; the mechanism remains under study.

GLP-1 fused to an antibody fragment, giving once-weekly dosing. Lowers glucose and, in a cardiovascular outcomes trial, the rate of major cardiovascular events.Schematic — not to scale

3What the research shows

Glucose control in type 2 diabetes

The AWARD programme (AWARD-1 to AWARD-11) tested dulaglutide against placebo, metformin, sitagliptin, exenatide, insulin glargine and liraglutide. Typical HbA1c reductions were 0.8–1.6 percentage points. In AWARD-6, 1.5 mg weekly was non-inferior to liraglutide 1.8 mg daily (Dungan 2014, Lancet). AWARD-11 showed that the higher 3 mg and 4.5 mg doses add roughly 0.2–0.3 further percentage points of HbA1c reduction and an extra 1–2 kg of weight loss over 1.5 mg (Frias 2021, Diabetes Care), leading to approval of those doses in 2020. [1][4]

Cardiovascular outcomes

REWIND (n=9,901, type 2 diabetes, only ~31% with prior cardiovascular disease — a lower-risk population than most such trials) found a 12% relative reduction in major adverse cardiovascular events over a median 5.4 years (hazard ratio 0.88), driven mainly by fewer non-fatal strokes (Gerstein 2019, Lancet). This supports a label indication for reducing cardiovascular events in people with type 2 diabetes with or without established cardiovascular disease. [2][3]

Graded A (secondary)

Kidney outcomes

In a REWIND secondary analysis dulaglutide reduced a composite kidney outcome, mostly through less new-onset macroalbuminuria (Gerstein 2019, Lancet, exploratory analysis). [2][3]

Graded A (modest)

Weight

Weight change in the AWARD trials was typically −2 to −3 kg at 1.5 mg and about −4 to −4.7 kg at 4.5 mg over 36–52 weeks. There are no trials in obesity without diabetes, and the drug is not approved for weight management. Head-to-head with semaglutide (SUSTAIN-7), semaglutide produced greater HbA1c and weight reductions (Pratley 2018, Lancet Diabetes Endocrinol). [5]

Children and adolescents

AWARD-PEDS (n=154, aged 10–17 with type 2 diabetes) showed HbA1c reductions vs placebo at 26 weeks with no effect on BMI (Arslanian 2022, NEJM), supporting paediatric approval. [6]

4Reported side effects and interactions

Literature-reported

Literature (common). nausea (~12–29% depending on dose, mostly in the first weeks), diarrhoea, vomiting, abdominal pain, decreased appetite, dyspepsia, fatigue; injection-site reactions are uncommon. GI events increase with the 3 mg and 4.5 mg doses.

Serious / label warnings. boxed warning for thyroid C-cell tumours in rodents, contraindicated with personal or family history of medullary thyroid carcinoma or MEN2; pancreatitis (rare); hypoglycaemia with insulin or sulfonylureas; acute kidney injury from dehydration; serious hypersensitivity; gallbladder disease; diabetic retinopathy complications (a small numerical excess of retinopathy events in REWIND, mirroring the semaglutide signal); heart rate increase of 2–4 bpm and first-degree AV block/PR prolongation in trials; delayed gastric emptying with aspiration risk under anaesthesia; a class-wide regulatory review of suicidal ideation found no causal link. Not for type 1 diabetes or pregnancy.

Community-reported

little off-label community use; where discussed, it is as a "gentler" weekly with less weight loss.

Immunogenicity. anti-drug antibodies in ~1–2% of users, usually without effect on efficacy.

Interactions. slowed absorption of oral medicines (monitor narrow-therapeutic-index drugs); additive hypoglycaemia with insulin and sulfonylureas.

Markers researchers commonly monitor

Following the approved-label monitoring and trial protocols:

Marker	Why it's watched
HbA1c and fasting glucose	primary efficacy measure; hypoglycaemia screening when combined with insulin or sulfonylureas.
eGFR and creatinine	kidney injury after GI fluid loss is a labelled risk; eGFR and urine albumin also track the kidney benefit seen in REWIND.
Lipid panel and blood pressure	small improvements in trials; relevant to cardiovascular benefit.
Heart rate and ECG (PR interval)	dulaglutide raised heart rate and PR interval slightly in trials; relevant for anyone with conduction disease.
Retinal exam	for anyone with existing diabetic retinopathy, per the REWIND signal.
Lipase/amylase	only if abdominal pain occurs.
Calcitonin	only on clinician advice, relating to the rodent thyroid C-cell warning.

Free for everyone. Safety information is never behind a paywall.

5Reconstitution and handling

Supplied as a single-dose pre-filled autoinjector pen or syringe needing no and no priming; the needle is hidden and the dose is fixed. Refrigerate; a pen left at room temperature for more than 14 days in total is discarded. As a fusion protein it is more sensitive to shaking and freezing than small peptides. No grey-market form is in meaningful circulation and the calculator does not apply.

Open in calculator, pre-loaded →

6Commonly studied alongside

Metformin, basal insulin (AWARD-9), SGLT2 inhibitors (AWARD-10), sulfonylureas. Compared head-to-head with liraglutide, exenatide and semaglutide. Tirzepatide succeeded it in Lilly's pipeline (SURPASS trials used dulaglutide as a comparator in SURPASS-J and in observational work).

Informational cross-links. Not stack recommendations.

7Regulatory status by region

Region	Status (checked —)
United States	FDA-approved (Trulicity, 2014) for type 2 diabetes in adults and children ≥10 years, and for reducing major cardiovascular events in adults with type 2 diabetes. 3 mg and 4.5 mg doses approved 2020. Intermittent shortages reported 2022–2024
European Union	EMA-authorised (2014); paediatric extension granted 2022 †
United Kingdom	MHRA-licensed; prescription-only
Australia	TGA-approved; PBS-listed for type 2 diabetes
South Africa	SAHPRA-registered; prescription-only
Sport	Not prohibited by WADA (GLP-1 agonists not listed as of 2026 †)

8Open questions

Whether the stroke-dominated cardiovascular benefit reflects a dulaglutide-specific effect or a class effect seen through the lens of a lower-risk population.
Why weight loss is smaller than with semaglutide or tirzepatide despite similar glucose effects — size, brain penetration, or receptor pharmacology.
Long-term paediatric outcomes beyond 26 weeks.

9References

1Dungan KM et al. (2014). 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. Lancet. PubMed
2Gerstein HC et al. (2019). Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. Lancet. PubMed · DOI
3Gerstein HC et al. (2019). Dulaglutide and renal outcomes in type 2 diabetes: an exploratory analysis of the REWIND randomised, placebo-controlled trial. Lancet. PubMed · DOI
4Frias JP et al. (2021). 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. PubMed · DOI
5Pratley RE 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. PubMed
6Arslanian SA et al. (2022). Once-weekly dulaglutide for the treatment of youths with type 2 diabetes. NEJM. PubMed · DOI
7Glaesner W et al. (2010). Engineering and characterization of the long-acting glucagon-like peptide-1 analogue LY2189265, an Fc fusion protein. Diabetes Metab Res Rev. PubMed · DOI
8Eli Lilly. Trulicity prescribing information (current label). PubMed

References are being resolved to PubMed/DOI identifiers; links search PubMed for the citation until then.

† Being confirmed by our reviewers against current sources.

10Community

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Self-reported side effects Phase 2

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11Page history

26 Oct 2026Profile published — awaiting medical review

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