Peptide Evidence Index

Dulaglutide

Evidence last reviewed: September 2026

Quick answers

What is it?: Dulaglutide is a GLP-1 receptor agonist, sold as Trulicity, that fuses a modified GLP-1 peptide to an antibody fragment for once-weekly dosing without the multi-step titration other GLP-1 drugs need.
Why are people interested in it?: Its defining trial, REWIND, is the largest and longest cardiovascular-outcomes trial run on any GLP-1 drug, and showed benefit even in people without existing heart disease.
What has actually been studied?: A single very large, long randomized trial (REWIND) in adults with type 2 diabetes, most without pre-existing cardiovascular disease, followed for a median 5.4 years.
How strong is the evidence?: Solid for its approved uses — diabetes and cardiovascular risk reduction — but it has never been tested in a dedicated weight-loss trial, so its evidence there is thinner than semaglutide's or tirzepatide's.
What don't we know yet?: What happens after stopping dulaglutide, and how it performs in adults younger than 50, since REWIND only enrolled older adults.
Where can I read the original research?: Sources at the bottom of this page: REWIND (Gerstein et al., Lancet 2019) and its companion renal-outcomes analysis.

Plain-English overview

Dulaglutide is a GLP-1 receptor agonist built differently from semaglutide, liraglutide, or tirzepatide: instead of a fatty-acid chain, a modified GLP-1 peptide is fused to a fragment of human IgG4 antibody, which slows its clearance and gives it a roughly five-day half-life for once-weekly dosing without a multi-week titration for most patients. It is FDA-approved as Trulicity for type 2 diabetes, with a cardiovascular-risk-reduction indication added in 2020, but it is not approved for weight management — its own manufacturer, Eli Lilly, developed tirzepatide separately for that use. Its defining trial, REWIND, is the largest and longest cardiovascular-outcomes trial run on any GLP-1 drug, and unlike most such trials it enrolled a majority of participants without pre-existing cardiovascular disease. Its weight-loss effect in trials was consistently smaller than semaglutide's or tirzepatide's, and it has not been tested in a dedicated obesity trial.

What researchers are studying it for

Type 2 diabetes (glycemic control)
Cardiovascular risk reduction in type 2 diabetes, with or without pre-existing cardiovascular disease

Current evidence level

Randomized trials

Regulatory status: Approved medicine. Evidence strength and approval are scored separately; approval is a regulatory decision about a specific use, not a measure of how much research exists.

Human research

REWIND (Gerstein et al., Lancet 2019) randomized 9,901 adults age 50 and older with type 2 diabetes to weekly dulaglutide 1.5 mg or placebo. Unlike LEADER or SELECT, about 69% of REWIND participants had cardiovascular risk factors rather than established cardiovascular disease. Over a median 5.4 years, the composite of non-fatal heart attack, non-fatal stroke, or cardiovascular death occurred in 12.0% of the dulaglutide group versus 13.4% with placebo, a hazard ratio of 0.88 — a smaller but real reduction, notable for showing benefit in a broader, lower-risk population than most cardiovascular-outcomes trials enroll. A companion analysis of the same trial (Gerstein et al., Lancet 2019) found dulaglutide also reduced a composite renal outcome — new macroalbuminuria, sustained kidney-function decline, or need for renal replacement therapy — with a hazard ratio of 0.85, driven mainly by less new macroalbuminuria. REWIND used a fixed once-weekly dose without the multi-week escalation schedule semaglutide and tirzepatide require for most patients, and it was designed to measure cardiovascular outcomes during continuous treatment rather than withdrawal effects, so what happens after stopping dulaglutide specifically has not been directly measured in a comparable trial.

Animal and preclinical research

As with other drugs in this class, rodent studies found thyroid C-cell tumors, the basis for dulaglutide's boxed warning and its contraindication in people with a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2. The source material reviewed here does not describe other animal studies in detail.

Major findings

REWIND: 12% relative reduction in cardiovascular death, heart attack, or stroke over a median 5.4 years in 9,901 adults with type 2 diabetes.
REWIND is one of the few large GLP-1 outcomes trials in which most participants (about 69%) had no pre-existing cardiovascular disease, extending the class's cardiovascular benefit beyond people who already have heart disease.
A companion REWIND analysis found a reduced composite renal outcome (hazard ratio 0.85), driven mainly by less new macroalbuminuria.
140 studies registered on ClinicalTrials.gov, with well over a hundred completed and posted.
Weight-loss magnitude was consistently smaller than semaglutide's or tirzepatide's in trials that measured it.

What has not been established

What happens after stopping dulaglutide — REWIND measured continuous treatment, not withdrawal.
Weight-loss effectiveness at a scale comparable to STEP 1, SCALE, or SURMOUNT-1 — dulaglutide has not been tested in a dedicated obesity trial.
Whether the rodent thyroid C-cell tumor signal applies to humans.
Effects in adults younger than 50 — REWIND's enrollment criteria specified 50 and older.

Important limitations

The pivotal trial excluded people with a history of pancreatitis or a personal/family history of medullary thyroid carcinoma or MEN2, as is standard for the class.
REWIND enrolled adults 50 and older specifically, so it does not speak directly to younger patients.
The registered trial base (140 studies) is smaller than semaglutide's or liraglutide's, consistent with a narrower approved-use footprint.
No dedicated withdrawal trial exists for dulaglutide comparable to semaglutide's STEP 1 extension or tirzepatide's SURMOUNT-4.

Regulatory status

Approved by the FDA as Trulicity in September 2014 for type 2 diabetes, with an added indication in 2020 for reducing the risk of major adverse cardiovascular events in adults with type 2 diabetes, based on REWIND. Not approved for weight management. Not on the World Anti-Doping Agency's Prohibited List.

Primary research sources

Gerstein HC et al., REWIND: Dulaglutide and Cardiovascular Outcomes in Type 2 Diabetes: Lancet 2019; PMID 31189511; ClinicalTrials.gov NCT01394952
Gerstein HC et al., REWIND renal outcomes companion analysis: Lancet 2019; PMID 31189509; ClinicalTrials.gov NCT01394952

Full evidence entry (complete data, registry records, dosing evidence)

Approved medicine

Approved by a major regulator for a specific use

At a glance

Also known as: Trulicity
Class: GLP-1 receptor agonist (fusion protein)
Derived from: A modified GLP-1 peptide fused to a fragment of human immunoglobulin G4 (IgG4-Fc), a construction that slows its clearance and gives it a half-life of about five days, allowing once-weekly dosing
Registered human trials: 140
…with published results: well over a hundred, including the pivotal trial cited below (counted on ClinicalTrials.gov this session)
Largest human trial: 9,901 adults with type 2 diabetes and either established cardiovascular disease or cardiovascular risk factors (REWIND, 2019) — dulaglutide reduced the composite of non-fatal heart attack, non-fatal stroke, or cardiovascular death by 12% versus placebo over a median 5.4 years
Studied for: type 2 diabetes (glycemic control), cardiovascular risk reduction in type 2 diabetes, with or without pre-existing cardiovascular disease
Dosing evidence: Prescribed by a clinicianThe approved dose is a fixed once-weekly injection set by the trial protocol and, in practice, by a prescriber following the FDA-approved label; unlike semaglutide and tirzepatide, most patients do not need a multi-step titration.
Regulatory status: Approved by the FDA as Trulicity in September 2014 for type 2 diabetes, with an added indication in 2020 for reducing the risk of major adverse cardiovascular events in adults with type 2 diabetes, based on REWIND. Not approved for weight management — Eli Lilly developed tirzepatide, a separate molecule, for that indication instead.
Anti-doping status: Not on the World Anti-Doping Agency's Prohibited List

What it is

Dulaglutide is a GLP-1 receptor agonist built differently from semaglutide, liraglutide, or tirzepatide: instead of a fatty-acid chain, it fuses a modified GLP-1 peptide to a fragment of human IgG4 antibody. That fusion protein clears slowly, giving dulaglutide a roughly five-day half-life and allowing once-weekly dosing without the multi-week titration schedule semaglutide and tirzepatide require for most patients.

It is FDA-approved as Trulicity for type 2 diabetes, with a cardiovascular-risk-reduction indication added in 2020. It is not approved for weight management; its own manufacturer developed and marketed tirzepatide, a different molecule, for that use instead.

What the studies actually found

REWIND (Gerstein et al., Lancet 2019; PubMed PMID 31189511, DOI31149-3)) is the largest and longest cardiovascular-outcomes trial run on a GLP-1 drug: 9,901 adults age 50 and older with type 2 diabetes, randomized to weekly dulaglutide 1.5 mg or placebo. Unlike LEADER or SELECT, most REWIND participants (about 69%) had cardiovascular risk factors rather than established cardiovascular disease. Over a median 5.4 years, the composite of non-fatal heart attack, non-fatal stroke, or cardiovascular death occurred in 12.0% of the dulaglutide group versus 13.4% with placebo (hazard ratio 0.88) — a smaller but real reduction, notable for showing benefit in a broader, lower-risk population than most cardiovascular-outcomes trials enroll.

A companion analysis of the same trial (Gerstein et al., Lancet 2019; PubMed PMID 31189509, DOI31150-X)) found dulaglutide also reduced a composite renal outcome — new macroalbuminuria, sustained kidney-function decline, or need for renal replacement therapy — with a hazard ratio of 0.85, driven mainly by less new macroalbuminuria.

What exists in humans

140 studies listing dulaglutide as an intervention are registered on ClinicalTrials.gov as of this session — a smaller registry than semaglutide's or liraglutide's, consistent with a narrower approved-use footprint of diabetes and cardiovascular risk only, with no weight-management indication pursued.

REWIND is notable for what it did not require: it is one of the few large GLP-1 outcomes trials in which a majority of participants had no pre-existing cardiovascular disease, which is why its result is often cited as evidence that this drug class's cardiovascular benefit is not limited to people who already have heart disease. It still excluded, as is standard for the class, people with a history of pancreatitis or a personal/family history of medullary thyroid carcinoma or MEN2, and it enrolled adults 50 and older specifically — it does not speak directly to younger patients.

What doses have been studied in humans

REWIND gave 9,901 adults with type 2 diabetes a fixed once-weekly subcutaneous injection of 1.5 mg, added to their existing diabetes regimen, followed for a median 5.4 years; the primary endpoint was time to a cardiovascular event, assessed at least every six months. Unlike the multi-week escalation schedules used for semaglutide and tirzepatide, the REWIND protocol did not require a titration period for most participants.

As with any prescription medicine, the specific dose a given patient receives is set by a prescriber against the FDA-approved label for that patient's clinical picture, not read off a trial protocol. Nothing here describes what a reader should take.

What remains unknown

What happens after stopping was not a focus of REWIND, which was designed to measure cardiovascular outcomes during continuous treatment rather than withdrawal effects. Class-wide data from semaglutide and tirzepatide trials suggests discontinuation likely reverses much of the metabolic benefit, but this has not been directly measured for dulaglutide in a comparable withdrawal trial.
Weight-loss magnitude was consistently smaller for dulaglutide than for semaglutide or tirzepatide in trials that measured it. REWIND was not designed or powered as a weight-loss trial, and dulaglutide has not been tested in a dedicated obesity trial comparable to STEP 1, SCALE, or SURMOUNT-1.
Thyroid C-cell tumors, flagged in rodent studies, carry the same boxed warning and unresolved human-risk question as the rest of the GLP-1 class.
Populations under 50 are not directly represented in REWIND's enrollment criteria.

Registry and study records

REWIND: Dulaglutide and Cardiovascular Outcomes in Type 2 Diabetes: ClinicalTrials.gov NCT01394952 · n=9,901, completed 2018, results posted; Gerstein et al., Lancet 2019

See the full Evidence Index →

Evidence last reviewed: September 2026. Peptide Proof reports what studies found. We do not give medical advice, dosing guidance, or treatment recommendations.