Dulaglutide

Origin and structure

Dulaglutide was developed by Eli Lilly under the code LY2189265 and is sold as Trulicity. Unlike semaglutide and liraglutide, which are small peptides carrying a fatty-acid chain, it is a large recombinant fusion protein, made in Chinese hamster ovary (CHO) cells. It consists of two identical chains held together by disulfide bridges. Each chain starts with a modified copy of human GLP-1 (positions 7 to 37), with glycine at position 8, glutamic acid at 22 and glycine at 36, followed by a linker of 16 amino acids and the Fc part of a human IgG4 antibody. The GLP-1 portion is about 90% identical to the natural hormone, and the whole molecule weighs about 63 kilodaltons.

Each change has its own job. Natural GLP-1 has a half-life of only 1.5 to 2 minutes, because the enzyme DPP-4 cuts off its first two amino acids and the kidneys clear it; the change at position 8, inside that stretch, makes dulaglutide resistant to DPP-4, and a further change was made in a stretch that could trigger an immune (T-cell) response. The antibody fragment makes the molecule too large for quick clearance by the kidneys and slows its uptake from under the skin, which gives a half-life of about five days. Dulaglutide was not designed to bind albumin, the mechanism semaglutide and liraglutide rely on. Lilly also modified the Fc fragment so that it binds less to the high-affinity Fc receptors of immune cells and does not fall apart into half-molecules; in the registration trials 1.6% of participants developed antibodies against dulaglutide.

Trulicity comes as single-use pre-filled pens holding 0.75, 1.5, 3 or 4.5 mg in 0.5 ml, for injection under the skin once a week.

How it works

Dulaglutide binds to the GLP-1 receptor and activates it. In the beta cells of the pancreas it raises cyclic AMP and so the release of insulin, but only when blood glucose is high, which is why on its own it seldom causes low blood sugar. In a pharmacodynamic study in people with type 2 diabetes it restored the first, rapid phase of insulin release after a glucose injection to a level above that of healthy volunteers on placebo. It also lowers glucagon, so the liver releases less glucose, and it slows the emptying of the stomach, most strongly after the first dose. Blood glucose falls from the first dose, and the effect holds through the whole week between injections.

Dulaglutide was developed and tested as a diabetes medicine, and its effect on weight is modest. In the main diabetes trials, body weight on 1.5 mg changed by between −0.35 and −2.90 kg from start to finish, and in AWARD-11 people lost 4.7 kg after 36 weeks on 4.5 mg. It is not authorised for weight management.

Is dulaglutide approved?

Yes, as a prescription medicine for type 2 diabetes in the EU and the US. It is not authorised for weight management or for type 1 diabetes.

In the Netherlands Trulicity is prescription-only, and the European marketing authorisation is held by Eli Lilly Nederland B.V. in Utrecht. Basic health insurance reimburses it only under the conditions in Annex 2 of the Regeling zorgverzekering. The Farmacotherapeutisch Kompas names dulaglutide, together with liraglutide and semaglutide, as the injectable GLP-1 agonists shown to work on hard cardiovascular and kidney end points in people at very high cardiovascular risk. For that group it advises starting with an SGLT2 inhibitor, or with a GLP-1 agonist when an SGLT2 inhibitor is contraindicated; if that is not enough, metformin is added first and then a GLP-1 agonist.

In June 2024 the EMA and the heads of the national medicines agencies issued recommendations to tackle shortages of four GLP-1 medicines, Trulicity among them. The shortages had affected EU countries since 2022 and were put down to higher demand and limited manufacturing capacity.

We do not sell dulaglutide. It is a recombinant protein made in mammalian cells, not a short synthetic peptide, and this article describes the licensed medicine Trulicity only.

• EU: Trulicity authorised throughout the EU on 21 November 2014 for adults with type 2 diabetes, on its own when metformin is unsuitable or added to other diabetes medicines. The REWIND results were added to the product information in October 2019; as with Ozempic, the cardiovascular benefit is described there rather than granted as a separate indication. The 3 and 4.5 mg pens followed in November 2020, and the indication was extended to children and adolescents from 10 years in March 2023.
• US: Trulicity approved on 18 September 2014 for adults with type 2 diabetes. In February 2020 the FDA added an indication to reduce major cardiovascular events in adults with type 2 diabetes who have established cardiovascular disease or multiple cardiovascular risk factors, in September 2020 the 3 and 4.5 mg doses, and in November 2022 children from 10 years. In March 2026 the label added that severe gastrointestinal reactions have also been reported with GLP-1 agonists after marketing, and listed intestinal obstruction and severe constipation with faecal impaction among its post-marketing reports.

What the research shows

The evidence comes from ten randomised phase 3 glucose trials with 8,035 adults, most of them part of Lilly's AWARD programme (Assessment of Weekly AdministRation of LY2189265 in Diabetes), from the REWIND cardiovascular outcomes trial and from a trial in young people. Dulaglutide was compared with placebo, metformin, sitagliptin, twice-daily exenatide, liraglutide and insulin glargine. In the five main studies assessed by the EMA, HbA1c fell after 26 weeks by 0.71 to 1.59 percentage points on 0.75 mg and by 0.78 to 1.64 points on 1.5 mg, depending on the trial. REWIND, AWARD-6 and AWARD-PEDS were funded by Eli Lilly. The headline results:

• REWIND (Lancet 2019): 9,901 people aged 50 or over with type 2 diabetes in 24 countries; only 31.5% had established cardiovascular disease, the others mostly had risk factors. Over a median 5.4 years, non-fatal heart attack, non-fatal stroke or cardiovascular death occurred in 12.0% on 1.5 mg weekly against 13.4% on placebo (hazard ratio 0.88, 95% CI 0.79 to 0.99). Death from any cause was 10.8% against 12.0%, not a significant difference (hazard ratio 0.90, 95% CI 0.80 to 1.01). Non-fatal stroke showed the clearest gap (2.7% against 3.5%; hazard ratio 0.76, 95% CI 0.61 to 0.95); non-fatal heart attack and cardiovascular death did not differ significantly.
• REWIND kidney analysis (Lancet 2019, exploratory): new heavy albumin loss in the urine, a sustained fall in eGFR of at least 30% or chronic kidney replacement therapy occurred in 17.1% against 19.6% (hazard ratio 0.85, 95% CI 0.77 to 0.93). The difference came mainly from fewer cases of new macroalbuminuria; the eGFR decline on its own was not significantly lower.
• AWARD-6 (Lancet 2014): 599 adults on metformin, head to head against daily liraglutide 1.8 mg; after 26 weeks HbA1c fell by 1.42 points on dulaglutide 1.5 mg against 1.36 on liraglutide, which met the test for non-inferiority. Weight fell by 2.90 kg against 3.61 kg.
• AWARD-11 (Diabetes Care 2021): 1,842 adults on metformin with a mean HbA1c of 8.6% and BMI of 34.2; after 36 weeks, counting only time on treatment, HbA1c fell by 1.53, 1.71 and 1.87 points and weight by 3.1, 4.0 and 4.7 kg on 1.5, 3 and 4.5 mg weekly. The 4.5 mg dose beat 1.5 mg on HbA1c and weight in both analyses; for 3 mg the HbA1c advantage held only when people who stopped treatment or needed rescue medication were left out.
• Chronic kidney disease: in a 52-week trial in adults with moderate to severe chronic kidney disease (eGFR 15 to 59), HbA1c fell as much on dulaglutide as on insulin glargine, with less than half the rate of documented low blood sugar (4.4 against 9.6 episodes per person per year).
• AWARD-PEDS (NEJM 2022): 154 young people aged 10 to 17 with type 2 diabetes; after 26 weeks HbA1c had risen by 0.6 points on placebo and fallen by 0.6 and 0.9 points on 0.75 and 1.5 mg. 51% on dulaglutide reached an HbA1c below 7%, against 14% on placebo; the change in BMI did not differ between the groups.

Side effects and warnings

The common side effects are gastrointestinal and rise with the dose. In the pooled placebo-controlled trials, nausea affected 12.4% on 0.75 mg and 21.1% on 1.5 mg against 5.3% on placebo, vomiting 6.0% and 12.7% against 2.3%, and diarrhoea 8.9% and 12.6% against 6.7%; decreased appetite, indigestion and fatigue were also more frequent. The complaints peak in the first two weeks and then fall off. In AWARD-11, nausea affected 13.4%, 15.6% and 16.4% on 1.5, 3 and 4.5 mg through 36 weeks, and 6.0%, 7.0% and 8.5% stopped because of side effects through 52 weeks. Over five years in REWIND, 47.4% on dulaglutide reported a gastrointestinal adverse event, against 34.1% on placebo.

The product information warns about acute pancreatitis (0.07% on dulaglutide against 0.14% on placebo in the registration trials), dehydration leading to kidney injury, severe gastrointestinal reactions including severe gastroparesis, gallstones and gallbladder inflammation, hypersensitivity reactions including rare anaphylaxis and angioedema, and low blood sugar when combined with insulin or a sulfonylurea: with a sulfonylurea plus metformin, about 40% had at least one documented episode. The resting heart rate rises by 2 to 4 beats per minute on average, and first-degree AV block was seen in 1.5 to 2.4%. Because dulaglutide slows stomach emptying, both labels warn about inhaling stomach contents under general anaesthesia or deep sedation. The US label adds that in REWIND, diabetic retinopathy complications were more frequent in people who already had retinopathy (8.5% against 6.2% on placebo).

Dulaglutide caused thyroid C-cell tumours in rats at three or more times the human exposure at 4.5 mg; a six-month study in transgenic mice found none, and whether it affects humans is unknown. The US label carries a boxed warning and rules out people with a personal or family history of medullary thyroid carcinoma and people with MEN 2; the EU product information describes the rat finding and lists only hypersensitivity as a contraindication. The EU product information advises against use in pregnancy and during breast-feeding, as does the Farmacotherapeutisch Kompas for pregnancy. Dulaglutide is not a substitute for insulin and is not for type 1 diabetes or diabetic ketoacidosis.

Dulaglutide versus semaglutide and tirzepatide

Semaglutide (Ozempic) is another weekly GLP-1 agonist for type 2 diabetes. In the head-to-head trial SUSTAIN 7, 1,201 adults on metformin were randomised to semaglutide 0.5 or 1 mg or dulaglutide 0.75 or 1.5 mg. After 40 weeks semaglutide 1 mg lowered HbA1c by 1.8 points against 1.4 for dulaglutide 1.5 mg, and weight by 6.5 kg against 3.0 kg. SUSTAIN 7 used the doses available at the time; dulaglutide 3 and 4.5 mg were added later.

Dulaglutide 1.5 mg has also served as the active comparator for newer drugs. SURPASS-CVOT chose it because it had been shown to reduce cardiovascular events: 13,299 adults with type 2 diabetes and atherosclerotic cardiovascular disease were randomised to tirzepatide or dulaglutide, with no placebo group; heart attack, stroke or cardiovascular death occurred in 12.2% against 13.1% (hazard ratio 0.92, 95.3% CI 0.83 to 1.01), so tirzepatide was non-inferior, not superior. Death from any cause, a secondary outcome, occurred in 8.6% against 10.2%. Mazdutide was also tested against dulaglutide, in DREAMS-2.

In REWIND, about two in three participants had cardiovascular risk factors but no established cardiovascular disease, so the trial also says something about people earlier in the course of the disease; the US indication covers both groups.

Frequently asked questions

What is the difference between Trulicity and Ozempic?

Both are weekly GLP-1 receptor agonist injections for type 2 diabetes, from different companies: Trulicity (dulaglutide) from Eli Lilly and Ozempic (semaglutide) from Novo Nordisk. Dulaglutide is a large protein built on an antibody fragment, semaglutide a peptide with a fatty-acid chain. In the head-to-head trial SUSTAIN 7, semaglutide 1 mg lowered HbA1c and weight more than dulaglutide 1.5 mg: 1.8 against 1.4 points, and 6.5 against 3.0 kg. Semaglutide is also authorised for weight management, as Wegovy; dulaglutide is not.

Do you lose weight on dulaglutide?

A little, but it is not a weight-loss medicine: Trulicity is authorised only for type 2 diabetes. In the main diabetes trials, people on 1.5 mg lost up to about 3 kg, and in AWARD-11 they lost 3.1 kg on 1.5 mg and 4.7 kg on 4.5 mg after 36 weeks. The medicines authorised for weight management produced far larger losses in their main obesity trials: 14.9% of body weight on Wegovy and up to 20.9% on Mounjaro.

Does Trulicity lower the risk of heart attack and stroke?

In people with type 2 diabetes, yes, modestly. In REWIND, 9,901 people aged 50 or over were followed for a median 5.4 years: a heart attack, stroke or cardiovascular death occurred in 12.0% on dulaglutide 1.5 mg against 13.4% on placebo, a 12% lower risk. Most participants had risk factors rather than established heart disease. The US label has a cardiovascular indication; in the EU the results are in the product information.

Is Trulicity available in the Netherlands, and is it reimbursed?

Yes, on prescription. Trulicity is registered in the Netherlands as pens of 0.75, 1.5, 3 and 4.5 mg, and basic health insurance reimburses it for type 2 diabetes under the conditions in Annex 2 of the Regeling zorgverzekering. It is not authorised for weight loss. We do not sell dulaglutide.

Is dulaglutide a peptide like semaglutide?

Only partly. Its active end is a modified GLP-1 peptide, but each of its two chains is fused to an antibody Fc fragment, which makes it a protein of about 63 kilodaltons, produced in hamster cells. Semaglutide and liraglutide are much smaller peptides that get their long action from a fatty-acid chain binding to albumin; dulaglutide gets it from the antibody fragment instead.

Is dulaglutide banned in sport?

No. GLP-1 receptor agonists, dulaglutide included, are not on the WADA Prohibited List, which the Dutch anti-doping rules also apply. WADA monitors the use of GLP-1 agonists such as semaglutide and tirzepatide, and when it published the 2027 List in September 2026 it left their status unchanged. Being monitored is not a ban. The Dopingautoriteit's Dopingwaaier shows the current status of individual medicines.

Storage and handling

Store according to product-label instructions and batch handling notes. Lyophilized research peptides are commonly kept dry, protected from light, and handled with clean laboratory technique.

References

Checked against these sources on 28 October 2026.

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