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Dulaglutide vs Semaglutide: What the SUSTAIN 7 Trial Shows

Two once-weekly GLP-1 receptor agonists for type 2 diabetes. One randomized trial, SUSTAIN 7, compared them directly on blood glucose and body weight. Their cardiovascular trials used placebo, not each other.

FDA Approved FDA Approved Active Comparator RCT Available
Comparison banner for dulaglutide and semaglutide, two once-weekly GLP-1 receptor agonists compared in the SUSTAIN 7 trial.
Dulaglutide and semaglutide both activate the GLP-1 receptor; SUSTAIN 7 compared them directly in type 2 diabetes. Illustration © Inside Peptides.
Evidence-Based Short Answer

Evidence-Based Summary

In SUSTAIN 7, a 40-week open-label trial in 1,201 adults with type 2 diabetes on metformin, semaglutide lowered HbA1c by about 0.4 percentage points more than dulaglutide at both dose levels tested, and reduced body weight by about 2.3 to 3.6 kg more. Gastrointestinal side effects were common with both. The trial tested the regimens available at the time, was funded by Novo Nordisk, and did not measure heart attacks or strokes. Both drugs reduced major cardiovascular events against placebo in separate trials (REWIND for dulaglutide; SELECT and others for semaglutide), but no trial has compared them on cardiovascular outcomes. Semaglutide also has approved weight-management and oral forms; 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 Semaglutide

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 Semaglutide.
Feature Dulaglutide Semaglutide
Drug class GLP-1 receptor agonist: two GLP-1 analogue chains fused to an antibody Fc fragment GLP-1 receptor agonist: GLP-1 analogue peptide 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-weekly injection (Ozempic, Wegovy) or once-daily tablet (Rybelsus, Ozempic and Wegovy tablets)
U.S. regulatory status FDA-approved (Trulicity): type 2 diabetes in adults and children 10+, cardiovascular risk reduction in type 2 diabetes FDA-approved: type 2 diabetes, cardiovascular and kidney risk reduction, and weight management, depending on product
Direct comparison SUSTAIN 7 comparator (40 weeks, type 2 diabetes) SUSTAIN 7: greater HbA1c and weight reduction than dulaglutide
Strongest outcomes evidence REWIND: fewer major cardiovascular events than placebo (HR 0.88) SELECT (no diabetes) and FLOW (type 2 diabetes with kidney disease) versus placebo
Main safety concerns Gastrointestinal effects; thyroid C-cell tumor boxed warning (rodent data); pancreatitis; diabetic retinopathy complications Gastrointestinal effects; thyroid C-cell tumor boxed warning (rodent data); pancreatitis; diabetic retinopathy complications
WADA status (2026) Not named on the Prohibited List Not named on the Prohibited List
Receptor Biology

Same Receptor, Different Molecular Designs

Both drugs activate the GLP-1 receptor, which helps glucose-dependent insulin release, lowers glucagon and reduces appetite. They differ in how they are built to last a week in the body, not in which receptor they target.

GLP-1 (Fc-fusion)

Dulaglutide

Primary Target: GLP-1 receptor

Affinity Profile: Selective GLP-1 receptor agonist

Two identical GLP-1 analogue chains are joined by a linker to a modified human IgG4 Fc fragment, giving a large (about 63 kDa) protein that lasts long enough for weekly injection.

GLP-1 (acylated peptide)

Semaglutide

Primary Targets: GLP-1 receptor

Affinity Profile: Selective GLP-1 receptor agonist

A modified GLP-1 peptide carrying a fatty-acid side chain, designed for once-weekly injection. Oral tablets contain the same molecule but are separate products with their own labels.

Regulatory Status

FDA Approvals and Indications

Checked 11 October 2026 against Drugs@FDA and DailyMed. An approval belongs to a named product, formulation 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 the risk of major adverse cardiovascular events in adults with type 2 diabetes who have established cardiovascular disease or multiple cardiovascular risk factors. It is not approved for weight management or type 1 diabetes.

FDA Approved

Semaglutide Status & Formulations

Ozempic injection is approved for glycemic control in adults with type 2 diabetes, to reduce major cardiovascular events in adults with type 2 diabetes and established cardiovascular disease, and to reduce kidney and cardiovascular-death risk in adults with type 2 diabetes and chronic kidney disease. Oral Rybelsus/Ozempic tablets have their own diabetes and cardiovascular indications. Wegovy injection and tablets cover defined weight-management and cardiovascular indications.

Critical Regulatory Distinction

Dulaglutide is not approved for weight management. Products sharing an ingredient are not interchangeable: Ozempic, Rybelsus and Wegovy each have their own indications. Compounded or online "research" semaglutide is not an FDA-approved equivalent.

Human Clinical Trials

Outcomes Trials for Each Medicine

Apart from SUSTAIN 7, the major trials compared each drug with placebo in different populations. These results cannot be used to rank the two drugs on heart or kidney outcomes.

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). All-cause death did not differ significantly (HR 0.90, 95% CI 0.80–1.01). Gastrointestinal adverse events were reported by 47.4% versus 34.1%.

Semaglutide: Clinical Evidence Overview

FLOW randomized 3,533 adults with type 2 diabetes and chronic kidney disease; its kidney and cardiovascular-death composite favoured semaglutide (HR 0.76, 95% CI 0.66–0.88). SELECT randomized 17,604 adults with cardiovascular disease and overweight or obesity but no diabetes: events occurred in 6.5% versus 8.0% with placebo (HR 0.80, 95% CI 0.72–0.90). STEP 1 showed −14.9% versus −2.4% weight change over 68 weeks in adults without diabetes.

Active-Comparator RCT

SUSTAIN 7: Semaglutide Versus Dulaglutide Added to Metformin in Type 2 Diabetes

SUSTAIN 7 is the only published randomized trial comparing these two drugs directly. It paired a lower dose of each drug and a higher dose of each drug. Results are reported here without dose amounts.

SUSTAIN 7: Phase 3b Head-to-Head Trial (Lancet Diabetes & Endocrinology, 2018)

Head-to-Head RCT

ClinicalTrials.gov: NCT02648204 · Study Design: Open-label, parallel-group, 40-week randomized trial at 194 sites in 16 countries.

Participant Population: 1,201 adults with type 2 diabetes and HbA1c 7.0–10.5% on metformin alone.

Assigned Interventions: Four arms, randomized 1:1:1:1: semaglutide (lower dose), dulaglutide (lower dose), semaglutide (higher dose), dulaglutide (higher dose), each once weekly. Trial regimens are context, not prescribing guidance.

Primary Endpoint: Change in HbA1c from baseline at week 40; body-weight change was the confirmatory secondary endpoint.

Direct Head-to-Head Findings

Table 2: Primary and key secondary outcomes from the SUSTAIN 7: Phase 3b Head-to-Head Trial (Lancet Diabetes & Endocrinology, 2018) trial.
Outcome Measure Dulaglutide Semaglutide Statistical Significance & Findings
HbA1c change, lower-dose pairing (percentage points) −1.1 (dulaglutide, lower dose) −1.5 (semaglutide, lower dose) Estimated treatment difference −0.40 points (95% CI −0.55 to −0.25); p<0.0001, favouring semaglutide.
HbA1c change, higher-dose pairing (percentage points) −1.4 (dulaglutide, higher dose) −1.8 (semaglutide, higher dose) Estimated treatment difference −0.41 points (95% CI −0.57 to −0.25); p<0.0001, favouring semaglutide.
Body-weight change, lower-dose pairing −2.3 kg (dulaglutide, lower dose) −4.6 kg (semaglutide, lower dose) Estimated treatment difference −2.26 kg (95% CI −3.02 to −1.51); p<0.0001.
Body-weight change, higher-dose pairing −3.0 kg (dulaglutide, higher dose) −6.5 kg (semaglutide, higher dose) Estimated treatment difference −3.55 kg (95% CI −4.32 to −2.78); p<0.0001.

Safety in SUSTAIN 7: Phase 3b Head-to-Head Trial (Lancet Diabetes & Endocrinology, 2018)

Gastrointestinal disorders were the most common adverse events: 33% (dulaglutide, lower dose), 48% (dulaglutide, higher dose), 43% (semaglutide, lower dose) and 44% (semaglutide, higher dose). They were also the most common reason for stopping treatment. Six deaths occurred: one in each semaglutide group and two in each dulaglutide group.

Essential Methodological Limitations

  • Open-label: participants and investigators knew which drug was assigned.
  • The primary analysis used on-treatment data before any rescue medication, which can differ from an intention-to-treat estimate.
  • Only the regimens available at the time were tested; the trial does not cover every dose now on either label or oral semaglutide.
  • Adults on metformin alone with type 2 diabetes; 40 weeks; no cardiovascular or kidney outcomes measured.
  • Funded by Novo Nordisk, the maker of semaglutide.
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 Semaglutide.
Study & Citation Population Comparison & Dosing Duration Main Endpoint Key Finding Methodological Limitations
SUSTAIN 7 (Pratley et al., Lancet Diabetes Endocrinol 2018) 1,201 adults with type 2 diabetes on metformin Semaglutide vs dulaglutide (lower and higher dose pairings) 40 weeks HbA1c and body weight HbA1c differences −0.40 and −0.41 points; weight differences −2.26 and −3.55 kg, favouring semaglutide. Open-label; industry-funded; no outcomes data.
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; does not compare with semaglutide.
FLOW (Perkovic et al., NEJM 2024) 3,533 adults with type 2 diabetes and chronic kidney disease Semaglutide vs placebo Median 3.4 years Kidney events or kidney/cardiovascular death HR 0.76 (95% CI 0.66–0.88). Stopped early after a prespecified interim analysis; placebo comparison.
SELECT (Lincoff et al., NEJM 2023) 17,604 adults with cardiovascular disease and overweight or obesity, no diabetes Semaglutide vs placebo Mean 39.8 months Major cardiovascular events 6.5% vs 8.0%; HR 0.80 (95% CI 0.72–0.90). No diabetes; different population from REWIND.
Safety & Tolerability

Shared GLP-1 Label Warnings

Both drugs carry the class warnings of GLP-1 receptor agonists. In SUSTAIN 7, overall gastrointestinal event rates overlapped between the two drugs.

Boxed Warning

FDA Boxed Warning: Risk of Thyroid C-Cell Tumors

Trulicity and the semaglutide labels carry a boxed warning for thyroid C-cell tumors seen in rodents; whether these drugs cause such tumors in humans is unknown. Both are contraindicated with a personal or family history of medullary thyroid carcinoma or MEN 2. This is a labelling warning, not a measured human cancer rate.

Table 4: Evidence-supported safety considerations and adverse-reaction frequency for Dulaglutide and Semaglutide.
Safety Consideration Dulaglutide Semaglutide
Most common adverse reactions Nausea, diarrhoea, vomiting, abdominal pain, decreased appetite Nausea, vomiting, diarrhoea, abdominal pain, constipation
Gastrointestinal disorders in SUSTAIN 7 33% (lower dose) and 48% (higher dose) 43% (lower dose) and 44% (higher dose)
Label warnings Pancreatitis, hypoglycemia with insulin or secretagogues, hypersensitivity, kidney injury from dehydration, severe GI reactions, diabetic retinopathy complications, gallbladder disease, aspiration under anaesthesia Pancreatitis, diabetic retinopathy complications, hypoglycemia with insulin or secretagogues, kidney injury from dehydration, severe GI reactions, hypersensitivity, gallbladder disease, aspiration under anaesthesia
Children Approved for type 2 diabetes from age 10 Ozempic is approved for adults; pediatric approvals differ by product
Pharmacological Commonalities

What Dulaglutide and Semaglutide Have in Common

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

Same receptor and class warnings

Both are selective GLP-1 receptor agonists with the same thyroid C-cell boxed warning and similar label precautions.

Cardiovascular benefit versus placebo

Each reduced major cardiovascular events against placebo in its own trial and has a cardiovascular indication in type 2 diabetes.

Once-weekly injection

Both are available as once-weekly injections for type 2 diabetes.

Distinguishing Features

Key Scientific & Clinical Differences

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

Direct glucose and weight results

In SUSTAIN 7, semaglutide lowered HbA1c and weight more than dulaglutide at both dose pairings tested.

Range of approved uses

Semaglutide has kidney-risk, weight-management and oral-tablet indications; dulaglutide is approved for type 2 diabetes (including children 10+) and cardiovascular risk reduction.

Molecular design

Dulaglutide is a large Fc-fusion protein; semaglutide is a fatty-acid-modified peptide.

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.

Semaglutide is better than dulaglutide at preventing heart attacks

Not established
Regulatory Context:

Both have FDA-approved cardiovascular indications in type 2 diabetes, based on separate placebo-controlled trials.

Scientific Reality:

SUSTAIN 7 measured HbA1c and weight, not cardiovascular events. REWIND, SELECT and FLOW each used placebo, in different populations.

Dulaglutide can be used for weight loss like semaglutide

Supported for approved use only
Regulatory Context:

Only specific semaglutide products (Wegovy) carry a weight-management indication.

Scientific Reality:

Dulaglutide lowered weight modestly in diabetes trials, but it is approved only for type 2 diabetes and cardiovascular risk reduction.

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; SUSTAIN 7 directly favoured semaglutide for HbA1c.

Dulaglutide: Strong Evidence
Semaglutide: Strong Evidence

Body weight

Dulaglutide's weight effects come from diabetes trials; semaglutide has dedicated obesity trials and a weight indication.

Dulaglutide: Moderate Evidence
Semaglutide: Strong Evidence

Cardiovascular outcomes

Each reduced events against placebo; they have not been compared on outcomes.

Dulaglutide: Strong Evidence
Semaglutide: Strong Evidence

Direct comparison on outcomes

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

Dulaglutide: Insufficient Evidence
Semaglutide: 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.

Outcome comparison

No randomized trial compares dulaglutide and semaglutide on cardiovascular, kidney or mortality outcomes.

Current dose ranges

SUSTAIN 7 tested the regimens available in 2016; it does not show how every currently labelled regimen compares.

Individual response

Average differences in HbA1c and weight do not predict how a particular person will respond or tolerate either drug.

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
    Semaglutide versus dulaglutide once weekly in patients with type 2 diabetes (SUSTAIN 7): a randomised, open-label, phase 3b trial
    Pratley RE et al. (2018) · Lancet Diabetes & Endocrinology.
    Open-label, 40 weeks, 1,201 adults on metformin; funded by Novo Nordisk.
    Direct Source DOI: 10.1016/S2213-8587(18)30024-X PubMed: 29397376
  2. Trial registry record
    Efficacy and Safety of Semaglutide Versus Dulaglutide as add-on to Metformin in Subjects With Type 2 Diabetes.
    ClinicalTrials.gov (2019).
    SUSTAIN 7 registry record; completed, 1,201 enrolled; sponsor Novo Nordisk.
    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. Kidney outcomes trial
    Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes
    Perkovic V et al. (2024) · New England Journal of Medicine.
    3,533 adults with type 2 diabetes and chronic kidney disease; funded by Novo Nordisk.
    Direct Source DOI: 10.1056/NEJMoa2403347 PubMed: 38785209
  5. Cardiovascular outcomes trial
    Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes
    Lincoff AM et al. (2023) · New England Journal of Medicine.
    17,604 adults with cardiovascular disease and overweight or obesity; funded by Novo Nordisk.
    Direct Source DOI: 10.1056/NEJMoa2307563 PubMed: 37952131
  6. Randomized controlled trial · Obesity
    Once-Weekly Semaglutide in Adults with Overweight or Obesity
    Wilding JPH et al. (2021) · New England Journal of Medicine.
    Double-blind, 68 weeks, 1,961 adults without diabetes; funded by Novo Nordisk.
    Direct Source DOI: 10.1056/NEJMoa2032183 PubMed: 33567185
  7. Official U.S. prescribing information
    Trulicity (dulaglutide) injection, current U.S. label
    DailyMed / National Library of Medicine (2026).
    Checked 11 October 2026.
    Direct Source
  8. FDA approval record
    Drugs@FDA: Trulicity, BLA 125469
    U.S. FDA (2026).
    Direct Source
  9. Official U.S. prescribing information
    Ozempic injection, current U.S. label
    DailyMed / National Library of Medicine (2026).
    Checked 11 October 2026.
    Direct Source
  10. Official U.S. prescribing information
    Rybelsus and Ozempic tablets, current U.S. label
    DailyMed / National Library of Medicine (2026).
    Checked 11 October 2026.
    Direct Source
  11. Official U.S. prescribing information
    Wegovy injection and tablets, current U.S. label
    DailyMed / National Library of Medicine (2026).
    Checked 11 October 2026.
    Direct Source