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Dulaglutide vs Liraglutide: What the AWARD-6 Trial Shows

Two FDA-approved GLP-1 receptor agonists that differ mainly in how often they are injected. The AWARD-6 trial compared them directly and found similar HbA1c lowering over 26 weeks.

FDA Approved FDA Approved Active Comparator RCT Available
Comparison banner for dulaglutide, a once-weekly GLP-1 receptor agonist, and liraglutide, a once-daily GLP-1 receptor agonist.
Once-weekly dulaglutide and once-daily liraglutide both activate the GLP-1 receptor; AWARD-6 compared them directly. Illustration © Inside Peptides.
Evidence-Based Short Answer

Evidence-Based Summary

In AWARD-6, a 26-week open-label trial in 599 adults with type 2 diabetes on metformin, once-weekly dulaglutide lowered HbA1c by 1.42 percentage points and once-daily liraglutide by 1.36, a difference of −0.06 points that met the trial's non-inferiority test. Gastrointestinal side effects and stopping for adverse events were similar. Both drugs reduced major cardiovascular events against placebo in separate trials (REWIND and LEADER), which cannot be compared with each other. Liraglutide is also approved for weight management (Saxenda) and is available as generic products; dulaglutide is approved for type 2 diabetes only.

Medical disclaimer: Inside Peptides provides educational, evidence-first scientific analysis. Decisions about any medicine depend on the approved indication, medical history and individual supervision by a licensed clinician. We do not provide treatment, dosing or sourcing recommendations.
At a Glance

Quick Comparison: Dulaglutide vs Liraglutide

A high-level comparison of molecule class, molecular receptor targets, FDA regulatory approvals, and verified clinical programs.

Table 1: Verified regulatory, pharmacological, and clinical comparison between Dulaglutide and Liraglutide.
Feature Dulaglutide Liraglutide
Drug class GLP-1 receptor agonist: GLP-1 analogue chains fused to an antibody Fc fragment GLP-1 receptor agonist: GLP-1 analogue with a fatty-acid side chain
Target receptor GLP-1 receptor GLP-1 receptor
How it is given Once-weekly injection under the skin Once-daily injection under the skin
U.S. regulatory status FDA-approved (Trulicity): type 2 diabetes in adults and children 10+, cardiovascular risk reduction FDA-approved: Victoza (type 2 diabetes, adults and children 10+; cardiovascular risk reduction) and Saxenda (weight management, adults and children 12+); generic products approved
Direct comparison AWARD-6: HbA1c −1.42 points AWARD-6: HbA1c −1.36 points (difference −0.06; non-inferior)
Cardiovascular outcomes trial REWIND vs placebo: HR 0.88 LEADER vs placebo: HR 0.87
Main safety concerns Gastrointestinal effects; thyroid C-cell tumor boxed warning (rodent data); pancreatitis Gastrointestinal effects; thyroid C-cell tumor boxed warning (rodent data); pancreatitis
WADA status (2026) Not named on the Prohibited List Not named on the Prohibited List
Receptor Biology

Same Receptor, Different Dosing Interval

Both drugs activate the GLP-1 receptor, which supports glucose-dependent insulin release, lowers glucagon and reduces appetite. Their structures differ in ways that set how often they must be injected.

Weekly Fc-fusion

Dulaglutide

Primary Target: GLP-1 receptor

Affinity Profile: Selective GLP-1 receptor agonist

Two identical GLP-1 analogue chains linked to a modified human IgG4 Fc fragment, forming a large (about 63 kDa) protein suited to once-weekly injection.

Daily acylated peptide

Liraglutide

Primary Targets: GLP-1 receptor

Affinity Profile: Selective GLP-1 receptor agonist

A GLP-1 analogue with one amino-acid substitution and a fatty-acid (palmitoyl) side chain, injected once daily.

Regulatory Status

FDA Approvals and Indications

Checked 11 October 2026 against Drugs@FDA and DailyMed. Each brand has its own indication and population.

FDA Approved

Dulaglutide Status & Formulations

Trulicity (BLA 125469, Eli Lilly) is approved as an adjunct to diet and exercise to improve glycemic control in adults and children aged 10 and older with type 2 diabetes, and to reduce major adverse cardiovascular events in adults with type 2 diabetes who have established cardiovascular disease or multiple cardiovascular risk factors.

FDA Approved

Liraglutide Status & Formulations

Victoza (NDA 022341, Novo Nordisk) is approved for glycemic control in adults and children aged 10 and older with type 2 diabetes, and to reduce major adverse cardiovascular events in adults with type 2 diabetes and established cardiovascular disease. Saxenda (NDA 206321) is approved, with diet and activity, for chronic weight management in adults and in children aged 12 and older with obesity and body weight above 60 kg. Generic liraglutide products are FDA-approved.

Critical Regulatory Distinction

Victoza and Saxenda contain the same molecule but are labelled for different uses and must not be combined. Dulaglutide has no weight-management indication.

Human Clinical Trials

Cardiovascular Outcomes Trials

REWIND and LEADER each compared one drug with placebo. They enrolled different populations (REWIND included many people without prior cardiovascular disease), so their hazard ratios cannot rank the drugs.

Dulaglutide: Clinical Evidence Overview

REWIND randomized 9,901 adults aged 50 and over with type 2 diabetes and either previous cardiovascular disease or risk factors. Over a median 5.4 years, a first major cardiovascular event occurred in 12.0% with dulaglutide versus 13.4% with placebo (HR 0.88, 95% CI 0.79–0.99). In AWARD-1, dulaglutide also lowered HbA1c more than twice-daily exenatide.

Liraglutide: Clinical Evidence Overview

LEADER randomized 9,340 adults with type 2 diabetes and high cardiovascular risk. Over a median 3.8 years, the primary cardiovascular outcome occurred in 13.0% with liraglutide versus 14.9% with placebo (HR 0.87, 95% CI 0.78–0.97). Cardiovascular death was lower (4.7% vs 6.0%; HR 0.78, 95% CI 0.66–0.93).

Active-Comparator RCT

AWARD-6: Once-Weekly Dulaglutide Versus Once-Daily Liraglutide in Type 2 Diabetes

AWARD-6 is the published randomized trial comparing these drugs directly. It was designed to test whether dulaglutide was no worse than liraglutide for HbA1c lowering (a non-inferiority margin of 0.4 points). Results are reported without dose amounts.

AWARD-6: Phase 3 Non-Inferiority Trial (Lancet, 2014)

Head-to-Head RCT

ClinicalTrials.gov: NCT01624259 · Study Design: Open-label, parallel-group, 26-week randomized trial at 62 sites in nine countries.

Participant Population: 599 adults with type 2 diabetes, HbA1c 7.0–10.0% and BMI 45 or lower, on metformin.

Assigned Interventions: Dulaglutide (the higher of its two original doses) once weekly versus liraglutide (its highest diabetes dose) once daily. Trial regimens are context, not prescribing guidance.

Primary Endpoint: Change in HbA1c from baseline at week 26 (non-inferiority).

Direct Head-to-Head Findings

Table 2: Primary and key secondary outcomes from the AWARD-6: Phase 3 Non-Inferiority Trial (Lancet, 2014) trial.
Outcome Measure Dulaglutide Liraglutide Statistical Significance & Findings
HbA1c change (percentage points) −1.42 (dulaglutide) −1.36 (liraglutide) Difference −0.06 points (95% CI −0.19 to 0.07); non-inferiority met (p<0.0001). Not shown to be superior.
Nausea 20% 18% Similar; no formal superiority test reported in the abstract.
Stopping study drug for adverse events 6% 6% Same rate in both groups.
Hypoglycaemia (events per patient-year) 0.34 0.52 Low in both; no severe hypoglycaemia reported.

Safety in AWARD-6: Phase 3 Non-Inferiority Trial (Lancet, 2014)

Gastrointestinal events were the most common: nausea 20% vs 18%, diarrhoea 12% vs 12%, dyspepsia 8% vs 6% and vomiting 7% vs 8% (dulaglutide vs liraglutide). Discontinuation for adverse events was 6% in each group.

Essential Methodological Limitations

  • Open-label: participants and investigators knew which drug was assigned.
  • Only 26 weeks; no cardiovascular or kidney outcomes measured.
  • Adults on metformin with BMI 45 or lower; results may differ in other groups.
  • Liraglutide was used at its diabetes dose, not as Saxenda for weight management.
  • Funded by Eli Lilly, the maker of dulaglutide.
Evidence Matrix

Curated Clinical Evidence Table

A curated selection of the primary studies behind each compound’s evidence profile. Results from different studies are not directly comparable.

Table 3: Key studies evaluating Dulaglutide and Liraglutide.
Study & Citation Population Comparison & Dosing Duration Main Endpoint Key Finding Methodological Limitations
AWARD-6 (Dungan et al., Lancet 2014) 599 adults with type 2 diabetes on metformin Weekly dulaglutide vs daily liraglutide 26 weeks Change in HbA1c −1.42 vs −1.36 points; difference −0.06 (95% CI −0.19 to 0.07); non-inferior. Open-label; short; industry-funded.
REWIND (Gerstein et al., Lancet 2019) 9,901 adults aged 50+ with type 2 diabetes Dulaglutide vs placebo Median 5.4 years Major cardiovascular events 12.0% vs 13.4%; HR 0.88 (95% CI 0.79–0.99). Placebo comparison; broader-risk population than LEADER.
LEADER (Marso et al., NEJM 2016) 9,340 adults with type 2 diabetes and high cardiovascular risk Liraglutide vs placebo Median 3.8 years Major cardiovascular events 13.0% vs 14.9%; HR 0.87 (95% CI 0.78–0.97). Placebo comparison; not comparable with REWIND.
AWARD-1 (Wysham et al., Diabetes Care 2014) 978 adults with type 2 diabetes on metformin and pioglitazone Dulaglutide vs exenatide vs placebo 52 weeks (placebo to 26) Change in HbA1c Both dulaglutide doses lowered HbA1c more than twice-daily exenatide and placebo at 26 weeks. Does not involve liraglutide.
Safety & Tolerability

Shared GLP-1 Label Warnings

Both drugs carry the class warnings for GLP-1 receptor agonists. In AWARD-6 their gastrointestinal side-effect rates were similar.

Boxed Warning

FDA Boxed Warning: Risk of Thyroid C-Cell Tumors

Trulicity, Victoza and Saxenda carry a boxed warning for thyroid C-cell tumors seen in rodents; whether these drugs cause such tumors in humans is unknown. All are contraindicated with a personal or family history of medullary thyroid carcinoma or MEN 2.

Table 4: Evidence-supported safety considerations and adverse-reaction frequency for Dulaglutide and Liraglutide.
Safety Consideration Dulaglutide Liraglutide
Most common adverse reactions Nausea, diarrhoea, vomiting, abdominal pain, decreased appetite Nausea, diarrhoea, vomiting, decreased appetite, dyspepsia, constipation (Victoza)
Gastrointestinal events in AWARD-6 Nausea 20%, diarrhoea 12%, vomiting 7% Nausea 18%, diarrhoea 12%, vomiting 8%
Hypoglycaemia Risk rises with insulin or insulin secretagogues Risk rises with insulin or secretagogues; higher in children regardless of other drugs (Victoza label)
Other label warnings Pancreatitis, hypersensitivity, kidney injury from dehydration, severe GI reactions, diabetic retinopathy complications, gallbladder disease Pancreatitis, kidney injury from dehydration, hypersensitivity, gallbladder disease, never sharing pens
Pharmacological Commonalities

What Dulaglutide and Liraglutide Have in Common

Where the two compounds overlap in biology, evidence or regulatory context.

Similar glucose lowering

AWARD-6 found no meaningful difference in HbA1c lowering over 26 weeks.

Cardiovascular benefit versus placebo

Each reduced major cardiovascular events in its own placebo-controlled trial and carries a cardiovascular indication.

Shared warnings

Both carry the thyroid C-cell boxed warning and GLP-1 class precautions.

Distinguishing Features

Key Scientific & Clinical Differences

Meaningful distinctions in mechanism, strength of evidence, safety and regulatory status.

Injection frequency

Dulaglutide is injected once a week; liraglutide once a day.

Weight-management approval

Liraglutide is approved for weight management as Saxenda; dulaglutide is not.

Generic availability

FDA has approved generic liraglutide products referencing Victoza; Trulicity is the only dulaglutide product listed in Drugs@FDA.

Inside Peptides Editorial Policy

Scientific Comparison vs Clinical Recommendations

Inside Peptides compares scientific evidence, receptor pharmacology, and official regulatory documents to advance public and professional understanding. We do not determine which compound is appropriate for an individual patient, rank medications with arbitrary scores, or recommend initiating or switching treatments.

Decisions about any medicine require a licensed healthcare professional who can weigh personal medical history, contraindications, interactions and monitoring needs. Unapproved peptides have no established safe use, and products sold as “research chemicals” are not the preparations studied in clinical research.

Evidence Verification

Approved Uses vs Online Claims

A critical scientific distinction between verified, FDA-approved clinical uses and unverified claims circulating on social media and vendor platforms.

Weekly dulaglutide works better than daily liraglutide

Not supported
Regulatory Context:

Both are FDA-approved for type 2 diabetes.

Scientific Reality:

AWARD-6 showed dulaglutide was non-inferior, not superior, for HbA1c (difference −0.06 points). Convenience differs; average glucose lowering was similar.

Dulaglutide is approved for weight loss like liraglutide

Not supported
Regulatory Context:

Approved uses belong to specific products and populations.

Scientific Reality:

Only liraglutide (as Saxenda) has a weight-management indication; Trulicity does not.

Claim-Level Certainty

Evidence Strength Across Clinical Domains

Inside Peptides evaluates scientific certainty at the claim level. Because clinical evidence varies significantly depending on the therapeutic endpoint evaluated, each domain is assessed independently.

Blood glucose in type 2 diabetes

Both have large randomized programs; AWARD-6 found similar HbA1c lowering.

Dulaglutide: Strong Evidence
Liraglutide: Strong Evidence

Cardiovascular outcomes

REWIND and LEADER each showed fewer events than placebo; not compared with each other.

Dulaglutide: Strong Evidence
Liraglutide: Strong Evidence

Weight management

Liraglutide has dedicated weight trials and an approved indication; dulaglutide does not.

Dulaglutide: Insufficient Evidence
Liraglutide: Strong Evidence

Direct comparison on outcomes

No trial has compared them on cardiovascular, kidney or death outcomes.

Dulaglutide: Insufficient Evidence
Liraglutide: Insufficient Evidence
Unresolved Questions

What Research Still Doesn’t Tell Us

Identifying open scientific questions, pending active-comparator trials, and areas where long-term clinical data remain incomplete.

Long-term direct comparison

AWARD-6 lasted 26 weeks; there is no long-term head-to-head trial on outcomes.

Current dose ranges

AWARD-6 did not test the higher dulaglutide regimens that the current Trulicity label allows.

Adherence in real life

Whether weekly injection improves adherence and outcomes compared with daily injection needs evidence outside short trials.

Related Compound Profiles

Individual profiles provide full molecular datasheets, CAS numbers, preclinical histories, and compound monographs.

Bibliography & Sources

Scientific & Regulatory References

Every pharmacological mechanism, clinical trial result, and regulatory approval cited on this page is traceable to official FDA prescribing documentation, ClinicalTrials.gov registries, or peer-reviewed medical publications.

  1. Randomized controlled trial · Head-to-head
    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
    Dungan KM et al. (2014) · Lancet.
    Open-label, 26 weeks, 599 adults on metformin; funded by Eli Lilly.
    Direct Source DOI: 10.1016/S0140-6736(14)60976-4 PubMed: 25018121
  2. Trial registry record
    A Study Comparing the Effect of Dulaglutide With Liraglutide in Type 2 Diabetes
    ClinicalTrials.gov (2014).
    AWARD-6 registry record; completed, 599 enrolled; sponsor Eli Lilly.
    Direct Source
  3. Cardiovascular outcomes trial
    Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial
    Gerstein HC et al. (2019) · Lancet.
    9,901 adults aged 50 and over; median follow-up 5.4 years; funded by Eli Lilly.
    Direct Source DOI: 10.1016/S0140-6736(19)31149-3 PubMed: 31189511
  4. Cardiovascular outcomes trial
    Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes
    Marso SP et al. (2016) · New England Journal of Medicine.
    9,340 adults with type 2 diabetes and high cardiovascular risk; median 3.8 years; funded by Novo Nordisk and NIH.
    Direct Source DOI: 10.1056/NEJMoa1603827 PubMed: 27295427
  5. Randomized controlled trial · Active comparator
    Efficacy and safety of dulaglutide added onto pioglitazone and metformin versus exenatide in type 2 diabetes in a randomized controlled trial (AWARD-1)
    Wysham C et al. (2014) · Diabetes Care.
    Direct Source DOI: 10.2337/dc13-2760 PubMed: 24879836
  6. Official U.S. prescribing information
    Trulicity (dulaglutide) injection, current U.S. label
    DailyMed / National Library of Medicine (2026).
    Checked 11 October 2026.
    Direct Source
  7. FDA approval record
    Drugs@FDA: Trulicity, BLA 125469
    U.S. FDA (2026).
    Direct Source
  8. Official U.S. prescribing information
    Victoza (liraglutide) injection, current U.S. label
    DailyMed / National Library of Medicine (2025).
    Checked 11 October 2026.
    Direct Source
  9. Official U.S. prescribing information
    Saxenda (liraglutide) injection, current U.S. label
    DailyMed / National Library of Medicine (2026).
    Checked 11 October 2026.
    Direct Source
  10. FDA approval record
    Drugs@FDA: Victoza, NDA 022341
    U.S. FDA (2026).
    Victoza approval record; generic liraglutide ANDAs are listed separately in Drugs@FDA (checked 11 October 2026).
    Direct Source