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Evidence: HighProtein, not a peptideFDA ApprovedGLP-1 receptor agonist (Fc fusion)FDA-Approved since 2014Type 2 Diabetes · Cardiovascular

Dulaglutide

Two GLP-1 analogues joined to the tail of an antibody, so that one injection lasts a week. It lowered major cardiovascular events in a trial of 9,901 people with and without previous heart disease, and lost head-to-head to semaglutide.

Dulaglutide (Trulicity) is a once-weekly GLP-1 receptor agonist for type 2 diabetes, labelled for adults and children 10 and older and for cutting cardiovascular risk. In REWIND it reduced major cardiovascular events by 12% over five years; nausea, vomiting and diarrhoea are its commonest costs.

View Dosing Data Read Research →
Overview

What is it?

Dulaglutide is a GLP-1 receptor agonist built on an antibody scaffold. Each molecule has two identical, disulfide-linked chains, and each chain carries a GLP-1 analogue at its tip, joined by a short linker to the Fc part of a modified human IgG4 heavy chain. The GLP-1 portion is 90% homologous to the natural hormone, with changes that stop the enzyme DPP-4 from cutting it, and the Fc portion was altered to avoid binding the high-affinity Fc receptors. The result is a protein of about 63 kilodaltons with an elimination half-life of about five days, which is why it is injected once a week. A 2014 review of its first approval described the same design: a DPP-IV-protected GLP-1 analogue covalently linked to a human IgG4-Fc heavy chain.

Eli Lilly developed it, and FDA approved Trulicity on September 18, 2014 (BLA 125469). Drugs@FDA lists later efficacy supplements, and the current label, published August 10, 2026, covers three things: glycaemic control with diet and exercise in adults and in children 10 years and older with type 2 diabetes, and reducing the risk of major adverse cardiovascular events in adults with type 2 diabetes who have established cardiovascular disease or multiple risk factors. The dose starts at 0.75 mg a week and can rise in 1.5 mg steps, at least four weeks apart, to a maximum of 4.5 mg.

Its defining trial is REWIND. From 2011 to 2013 it enrolled 9,901 people with type 2 diabetes, mean age 66 and 46% women, with a median HbA1c of 7.2%, with and without previous cardiovascular disease. Over a median 5.4 years, the composite of cardiovascular death, heart attack or stroke occurred in 12.0% on dulaglutide 1.5 mg and 13.4% on placebo (hazard ratio 0.88, 95% CI 0.79 to 0.99). All-cause death did not differ significantly (HR 0.90, 0.80 to 1.01), and gastrointestinal adverse events were more common (47.4% against 34.1%). Exploratory analyses of the same trial found fewer renal events, mainly less new macroalbuminuria (HR 0.77), and a possible reduction in cognitive impairment that reached significance only after post-hoc adjustment.

Against other drugs it is the benchmark more often than the winner. In SUSTAIN 7, 1,201 people were randomised to semaglutide or dulaglutide at low and high doses: semaglutide lowered HbA1c more (1.8 against 1.4 points at the higher doses) and weight more (6.5 against 3.0 kg). In SURPASS-CVOT, 13,165 people with atherosclerotic disease received tirzepatide or dulaglutide, and major cardiovascular events occurred in 12.2% and 13.1% (HR 0.92), non-inferior but not superior. Newer agents, among them mazdutide in a Chinese phase III trial, have used dulaglutide 1.5 mg as the comparator and beaten it on weight.

Its own dose trials and special populations fill in the rest. Raising the dose to 4.5 mg lowered HbA1c by 1.77 points against 1.54 on 1.5 mg and weight by 4.6 against 3.0 kg at 36 weeks, at the cost of more nausea (16.4% against 13.4%) and vomiting (9.3% against 5.6%). In 577 people with moderate-to-severe chronic kidney disease it controlled glucose as well as insulin glargine, with less symptomatic hypoglycaemia and a slower fall in kidney function. In 154 young people aged 10 to 17, it lowered HbA1c against placebo and 51% reached an HbA1c under 7%, against 14%, without changing BMI.

Outside diabetes the evidence is early. In a Swiss trial of people trying to stop smoking, those who drank at the start and received dulaglutide drank 29% less over 12 weeks than those on placebo. Observational studies of large insurance and veterans' databases suggest broadly similar gastrointestinal, kidney and cardiovascular risks to semaglutide and liraglutide, with differences that such designs cannot settle.

The label carries the class warnings: a boxed warning about thyroid C-cell tumours in rats, with contraindication in people with a personal or family history of medullary thyroid carcinoma or MEN 2; pancreatitis; hypoglycaemia with insulin or sulfonylureas; serious hypersensitivity; kidney injury from dehydration; severe gastrointestinal reactions, added to the warnings in March 2026, with a recommendation against use in severe gastroparesis; complications of diabetic retinopathy; gallbladder disease; and aspiration during anaesthesia. In REWIND, retinopathy complications occurred in 1.9% on dulaglutide and 1.5% on placebo, and in 8.5% against 6.2% of those with retinopathy at the start. In sport, dulaglutide is not on WADA's Prohibited List.

HR 0.88
major cardiovascular events
REWIND, 9,901 people, 5.4 years
~5 days
half-life
one injection a week (label)
−1.4 vs −1.8
HbA1c points against semaglutide
SUSTAIN 7, higher doses
4.5 mg
maximum weekly dose
from 0.75 mg, in 1.5 mg steps (label)
Science

Mechanism of Action

Dulaglutide activates the GLP-1 receptor the way the gut hormone does after a meal, but it is built to last a week instead of minutes. What it does to glucose, appetite and the stomach follows from that receptor; how long it does it follows from the antibody fragment.

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Insulin when glucose is high

Dulaglutide raises cyclic AMP in pancreatic beta cells, which releases insulin in a glucose-dependent way, and it lowers glucagon (label); with insulin or a sulfonylurea it can cause low blood sugar.

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A slower stomach

It slows gastric emptying (label). Weight falls modestly, 3.0 kg on 1.5 mg in SUSTAIN 7, and nausea, vomiting and diarrhoea are its commonest side effects.

🛡

Built to resist breakdown

Changes in the GLP-1 portion stop DPP-4, the enzyme that breaks native GLP-1 down, from cutting it, and the IgG4-Fc fusion makes the molecule large; together they give a half-life of about 5 days (label).

♥

Cardiovascular and kidney outcomes

Over 5.4 years in REWIND it reduced major cardiovascular events (HR 0.88) and, in an exploratory analysis, new macroalbuminuria (HR 0.77).

Evidence

Published Research

PubMed returns about 1,300 records for dulaglutide. Our evidence set holds 43 papers; 34 name it in their titles and have an abstract, and 16 are carded below: 15 studies in people and 1 review. As a widely used approved drug, its evidence runs from registration trials and a five-year outcomes trial to head-to-head comparisons and large observational studies.

Review2014

First global approval

Eli Lilly's long-acting GLP-1 receptor agonist consists of a DPP-IV-protected GLP-1 analogue covalently linked to a human IgG4-Fc heavy chain by a small peptide linker. At the time of writing it was approved for type 2 diabetes in the US, recommended for approval in the EU and under review elsewhere.

PMID: 25367716
Human2019

REWIND: cardiovascular outcomes, 9,901 people

Over a median 5.4 years, cardiovascular death, heart attack or stroke occurred in 12.0% on dulaglutide 1.5 mg and 13.4% on placebo (HR 0.88, 95% CI 0.79 to 0.99). All-cause death was 10.8% against 12.0% (HR 0.90, 0.80 to 1.01). Gastrointestinal adverse events were reported by 47.4% against 34.1%. Median baseline HbA1c was 7.2% and 46% were women.

PMID: 31189511
Human2019

REWIND: kidney outcomes

In an exploratory analysis, the composite renal outcome occurred in 17.1% on dulaglutide and 19.6% on placebo (HR 0.85, 0.77 to 0.93). The clearest effect was on new macroalbuminuria (HR 0.77); a sustained eGFR decline of 30% or more (HR 0.89, 0.78 to 1.01) and chronic dialysis or transplant (HR 0.75, 0.39 to 1.44) were not significantly reduced.

PMID: 31189509
Human2020

REWIND: cognitive impairment

Among 8,828 participants with cognitive testing, substantive cognitive impairment occurred at 4.05 against 4.35 per 100 patient-years (HR 0.93, 0.85 to 1.02). After post-hoc adjustment for baseline scores the hazard was 14% lower (HR 0.86); the authors call for trials focused on brain health.

PMID: 32562683
Human2018

SUSTAIN 7: against semaglutide, 1,201 people

HbA1c fell 1.5 points on semaglutide 0.5 mg against 1.1 on dulaglutide 0.75 mg, and 1.8 against 1.4 at 1.0 and 1.5 mg; weight fell 4.6 against 2.3 kg and 6.5 against 3.0 kg. Gastrointestinal disorders affected 43%, 44%, 33% and 48% of the four groups.

PMID: 29397376
Human2021

AWARD-11: 3.0 and 4.5 mg against 1.5 mg

In metformin-treated adults over 52 weeks, 4.5 mg lowered HbA1c by 1.77 points against 1.54 on 1.5 mg at 36 weeks and weight by 4.6 against 3.0 kg; 3.0 mg was superior on one analysis only. Nausea rose from 13.4% to 16.4% and vomiting from 5.6% to 9.3% with the higher dose.

PMID: 33397768
Human2018

AWARD-7: moderate-to-severe kidney disease, 577 people

Against insulin glargine, HbA1c fell 1.2 and 1.1 points on dulaglutide 1.5 and 0.75 mg and 1.1 on glargine (non-inferior), with less symptomatic hypoglycaemia (4.4 and 4.3 against 9.6 events per patient-year) and a slower eGFR decline; nausea was 20% and 14% against 5%. End-stage kidney disease: 4%, 7% and 8%.

PMID: 29910024
Human2018

AWARD-10: added to SGLT2 inhibitors, 424 people

Added to an SGLT2 inhibitor, with or without metformin, dulaglutide gave significant and clinically relevant improvements in glycaemic control against placebo. Nausea affected 15% on 1.5 mg, 5% on 0.75 mg and 4% on placebo; one severe hypoglycaemia occurred on 0.75 mg.

PMID: 29483060
Human2022

AWARD-PEDS: youths with type 2 diabetes, 154 people

In 10- to 17-year-olds over 26 weeks, HbA1c rose 0.6 points on placebo and fell 0.6 and 0.9 on 0.75 and 1.5 mg; 51% on dulaglutide reached an HbA1c under 7.0% against 14%. BMI did not change differently, and gastrointestinal adverse events were more frequent, consistent with adults.

PMID: 35658022
Human2025

SURPASS-CVOT: against tirzepatide, 13,165 people

In type 2 diabetes with atherosclerotic cardiovascular disease, cardiovascular death, heart attack or stroke occurred in 12.2% on tirzepatide and 13.1% on dulaglutide (HR 0.92, 95.3% CI 0.83 to 1.01): tirzepatide was non-inferior, not superior. Gastrointestinal adverse events were more common with tirzepatide.

PMID: 41406444
Human2026

Against mazdutide in China

In a phase III trial in Chinese adults with type 2 diabetes, mazdutide 4 and 6 mg lowered HbA1c and body weight more than dulaglutide 1.5 mg over 28 weeks (weight differences -3.78% and -5.76%), with more gastrointestinal adverse events.

PMID: 41407860
Human2023

Alcohol during smoking cessation

In a secondary analysis of a trial in people trying to quit smoking, the 151 who drank alcohol at baseline and completed 12 weeks drank 29% less on dulaglutide than on placebo (relative effect 0.71, 95% CI 0.52 to 0.97), unrelated to whether they had stopped smoking.

PMID: 37991022
Human2026

Severe gastrointestinal events, US cohorts

Across propensity-matched cohorts of adults with type 2 diabetes (65,238 pairs for semaglutide against dulaglutide, 20,893 for tirzepatide against dulaglutide), the risk of severe gastrointestinal adverse events was similar (HR 0.96 in both comparisons); the authors note possible residual confounding.

PMID: 41183330
Human2025

Against liraglutide and semaglutide in veterans

In US veterans starting one of the three drugs, kidney and cardiovascular risks were similar. Liraglutide was associated with lower all-cause mortality than dulaglutide (HR 0.69), and dulaglutide with fewer gallstones than semaglutide (HR 0.72). The authors ask for head-to-head trials.

PMID: 41082229
Human2025

Against empagliflozin in routine care

In an observational comparison, death, heart attack or stroke risk was similar for dulaglutide and empagliflozin users (HR 1.03, 95% CI 0.90 to 1.16), while semaglutide showed some advantage over empagliflozin.

PMID: 40523289
Human2024

Dementia against SGLT2 inhibitors, Korea

In a population-based cohort, dementia risk did not clearly differ between people starting SGLT2 inhibitors and dulaglutide (risk ratio 0.81, 95% CI 0.56 to 1.16); the authors note residual confounding and that newer GLP-1 drugs were not studied.

PMID: 39186787
Dosing

Dosing Data

Dulaglutide is dosed by label from a single-dose pen, once a week on the same day, with or without food. The steps are set by glucose control and tolerance, not by weight.

Prescription medicine for type 2 diabetes and cardiovascular risk reduction. Do not use it with a personal or family history of medullary thyroid carcinoma or MEN 2; gastrointestinal effects, pancreatitis and hypoglycaemia with insulin or sulfonylureas are why dose changes are made with the prescriber.
ProtocolDoseFrequencyDurationRoute
Adults: start Approved labelTrulicity (dulaglutide) injection US prescribing information (DailyMed version 62, effective June 16, 2026)0.75 mgOnce weeklyAt least 4 weeksSubcutaneous pen
Adults: step up if needed Approved labelTrulicity (dulaglutide) injection US prescribing information (DailyMed version 62, effective June 16, 2026)1.5 mg, then 3 mg, then 4.5 mgOnce weeklyAt least 4 weeks per stepSubcutaneous pen
Children 10 years and older Approved labelTrulicity (dulaglutide) injection US prescribing information (DailyMed version 62, effective June 16, 2026)0.75 mg, may increase to 1.5 mgOnce weeklyPer labelSubcutaneous pen
REWIND (cardiovascular trial) Human studyPMID 311895111.5 mgOnce weeklyMedian 5.4 yearsSubcutaneous

Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.

A pre-dosed pen
Trulicity comes in single-dose pens of 0.75, 1.5, 3 and 4.5 mg, so no reconstitution calculation applies.
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Safety

Side Effects & Contraindications

Reported Side Effects

From the label and the studies above.

● Nausea, vomiting and diarrhoea: gastrointestinal events in 47.4% against 34.1% on placebo in REWIND, rising with dose (nausea 16.4% at 4.5 mg)
● Severe gastrointestinal reactions (label warning added March 2026); not recommended in severe gastroparesis
● Hypoglycaemia when combined with insulin or a sulfonylurea
● Acute pancreatitis, gallbladder disease and kidney injury from dehydration (label)
● Diabetic retinopathy complications: 1.9% against 1.5% in REWIND, 8.5% against 6.2% with prior retinopathy
● Serious hypersensitivity, and aspiration during anaesthesia or deep sedation (label)

Contraindications & Cautions

From the label; a clinician decides.

● Personal or family history of medullary thyroid carcinoma, or MEN 2
● Previous serious hypersensitivity to dulaglutide
● Severe gastroparesis: not recommended
● History of diabetic retinopathy: monitored
● Planned surgery or sedation: tell the team, because of aspiration risk
Questions

Frequently Asked Questions

?What is dulaglutide approved for?

In the US, Trulicity is approved to improve blood sugar control, with diet and exercise, in adults and children 10 years and older with type 2 diabetes, and to reduce the risk of major cardiovascular events in adults with type 2 diabetes who have heart disease or several risk factors. It is not approved for weight loss.

?Does dulaglutide protect the heart?

In REWIND, 9,901 people with type 2 diabetes, with and without previous heart disease, had fewer cardiovascular deaths, heart attacks or strokes on dulaglutide over 5.4 years: 12.0% against 13.4% (HR 0.88). All-cause death did not differ significantly.

?How does it compare with semaglutide and tirzepatide?

In SUSTAIN 7, semaglutide lowered HbA1c and weight more than dulaglutide at matched dose levels. In SURPASS-CVOT, tirzepatide was non-inferior to dulaglutide for cardiovascular events (12.2% against 13.1%), not superior.

?How much weight do people lose on dulaglutide?

Less than on newer drugs: about 3.0 kg on 1.5 mg in SUSTAIN 7 and 4.6 kg on 4.5 mg at 36 weeks in AWARD-11. It has no weight-management indication.

?Is dulaglutide banned in sport?

No. GLP-1 receptor agonists are not on WADA's 2026 or 2027 Prohibited Lists; the Legal table below gives the dataset's entry.

Bibliography

References

  1. [fda-pi] Trulicity (dulaglutide) injection Prescribing Information. Eli Lilly and Company (DailyMed version published 2026-08-10, read 2026-09-28).
  2. [fda-pi] US FDA, Drugs@FDA: Trulicity (dulaglutide), BLA 125469, approved 2014-09-18; efficacy supplements approved 2017-01-27, 2018-06-29, 2019-01-15, 2020-02-21, 2020-09-03 and 2022-11-17 (read 2026-09-28).
  3. [pubmed] Sanford M. "Dulaglutide: first global approval." Drugs, 2014;74(17):2097-103. PMID: 25367716.
  4. [pubmed] Gerstein HC, et al. "Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial." Lancet, 2019;394(10193):121-130. PMID: 31189511.
  5. [pubmed] Gerstein HC, et al. "Dulaglutide and renal outcomes in type 2 diabetes: an exploratory analysis of the REWIND randomised, placebo-controlled trial." Lancet, 2019;394(10193):131-138. PMID: 31189509.
  6. [pubmed] Cukierman-Yaffe T, et al. "Effect of dulaglutide on cognitive impairment in type 2 diabetes: an exploratory analysis of the REWIND trial." Lancet Neurol, 2020;19(7):582-590. PMID: 32562683.
  7. [pubmed] Pratley RE, et al. "Semaglutide versus dulaglutide once weekly in patients with type 2 diabetes (SUSTAIN 7): a randomised, open-label, phase 3b trial." Lancet Diabetes Endocrinol, 2018;6(4):275-286. PMID: 29397376.
  8. [pubmed] Frias JP, et al. "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, 2021;44(3):765-773. PMID: 33397768.
  9. [pubmed] Tuttle KR, et al. "Dulaglutide versus insulin glargine in patients with type 2 diabetes and moderate-to-severe chronic kidney disease (AWARD-7): a multicentre, open-label, randomised trial." Lancet Diabetes Endocrinol, 2018;6(8):605-617. PMID: 29910024.
  10. [pubmed] Ludvik B, et al. "Dulaglutide as add-on therapy to SGLT2 inhibitors in patients with inadequately controlled type 2 diabetes (AWARD-10): a 24-week, randomised, double-blind, placebo-controlled trial." Lancet Diabetes Endocrinol, 2018;6(5):370-381. PMID: 29483060.
  11. [pubmed] Arslanian SA, et al. "Once-Weekly Dulaglutide for the Treatment of Youths with Type 2 Diabetes." N Engl J Med, 2022;387(5):433-443. PMID: 35658022.
  12. [pubmed] Nicholls SJ, et al. "Cardiovascular Outcomes with Tirzepatide versus Dulaglutide in Type 2 Diabetes." N Engl J Med, 2025;393(24):2409-2420. PMID: 41406444.
  13. [pubmed] Guo L, et al. "Mazdutide versus dulaglutide in Chinese adults with type 2 diabetes." Nature, 2026;652(8108):181-188. PMID: 41407860.
  14. [pubmed] Probst L, et al. "Effects of dulaglutide on alcohol consumption during smoking cessation." JCI Insight, 2023;8(22). PMID: 37991022.
  15. [pubmed] Crisafulli S, et al. "Comparative Gastrointestinal Safety of Dulaglutide, Semaglutide, and Tirzepatide in Adults With Type 2 Diabetes." Ann Intern Med, 2026;179(1):1-11. PMID: 41183330.
  16. [pubmed] Derington CG, et al. "Liraglutide vs Semaglutide vs Dulaglutide in Veterans With Type 2 Diabetes." JAMA Netw Open, 2025;8(10):e2537297. PMID: 41082229.
  17. [pubmed] Saeed A, et al. "Comparison of Semaglutide or Dulaglutide Versus Empagliflozin for Risk for Death and Cardiovascular Outcomes Among Patients With Type 2 Diabetes : Two Target Trial Emulation Studies." Ann Intern Med, 2025;178(7):930-939. PMID: 40523289.
  18. [pubmed] Hong B, et al. "Sodium-Glucose Cotransporter-2 Inhibitors, Dulaglutide, and Risk for Dementia : A Population-Based Cohort Study." Ann Intern Med, 2024;177(10):1319-1329. PMID: 39186787.

Sources & Citations

Every PubMed citation on this page has been checked against its record. The Trulicity label (DailyMed, published August 10, 2026) and Drugs@FDA were read on September 28, 2026. Grey Peptides sells nothing and links to no vendor.

Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.

Last reviewed: 2026-09-28