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Type 1 Diabetes MellitusPhase 2TIRTLE2NCT06820281

Acute Metabolic Effects of Tirzepatide in Type 1 Diabetes

A Phase 2 study testing Tirzepatide 2.5mg weekly in people with Type 1 Diabetes Mellitus, run by Victor Chang Cardiac Research Institute at 1 site in Australia.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

This study will examine the effects of Tirzepatide (TZP), a glucagon-like peptide 1 (GLP1) - gastric inhibitory peptide (GIP) co-agonist, on metabolism in type 1 diabetes (T1D). Research participants with T1D will undergo measures of insulin sensitivity, and hormone levels post-meal, post-hypoglycemia and during the… Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Type 1 Diabetes Mellitus
What is being tested?
Tirzepatide 2.5mg weekly
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
44 participants
Where
1 siteAustralia
Study dates
7 Jul 2026to 31 Dec 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • age 18-70 years
  • BMI ≥ 25 kg/m2
  • HbA1c ≤ 9.0%
  • insulin delivery using an automated insulin delivery system
  • at least 2 years since diagnosis of type 1 diabetes

Who cannot join

  • TZP or GLP-1 receptor agonist in last 3 months; metformin or sodium glucose co-transporter 2 (SGLT2) inhibitor in the last 6 weeks; systemic steroids, antipsychotics, in the last 6 weeks.
  • Hypoglycemic unawareness or severe hypoglycemia last 6 months.
  • History of seizure disorder.
  • History of weight loss surgery.
  • eGFR <60 mL/min/1.73 m2.
  • Liver disease (known cirrhosis, LFTs > 3x upper limit of normal).
Show all 11Show fewer
  • Active malignancy.
  • Pregnant, breastfeeding, planning pregnancy within 6 months, or not using adequate contraception.
  • Coronary event or stroke in last 6 months
  • Active or untreated proliferative diabetic retinopathy
  • Hemoglobin level < 13.5 g/dL in men, < 12.0 g/dL in women

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Jennifer R Snaith, MD PHD contact

+61 2 9295 8600

j.snaith@victorchang.edu.au

Jerry R Greenfield, MD PHD contact

j.greenfield@victorchang.edu.au

Australia1 site, 1 recruiting

  • Victor Chang Cardiac Research Institute

    Sydney, New South Wales, 2010

    Jennifer R Snaith, MD/PhD, 61 2 9295 8600, j.snaith@victorchang.edu.au

    Jennifer R Snaith, MD PHD

    Recruiting

Other trials in Australia

About this study

Official title: Acute Metabolic Effects of Tirzepatide in Type 1 Diabetes: a Phase 2 Double Blinded Placebo Controlled Clinical Trial (TIRTLE2)

This study will examine the effects of Tirzepatide (TZP), a glucagon-like peptide 1 (GLP1) - gastric inhibitory peptide (GIP) co-agonist, on metabolism in type 1 diabetes (T1D). Research participants with T1D will undergo measures of insulin sensitivity, and hormone levels post-meal, post-hypoglycemia and during the overnight period. These measures will be performed prior to, and after 6 weeks of treatment with TZP or placebo.

Read the detailed description

TIRTLE2 is a phase 2 double-blinded placebo-controlled mechanistic clinical trial that extends upon the findings of TIRTLE1, a phase 2 double-blinded placebo-controlled trial (TZP 5.0mg vs placebo over 12 weeks) in T1D (trial registration: ACTRN12624000111572).

TIRTLE2 is a designed to determine whether TZP can 1) improve whole body insulin sensitivity, 2) reduce prandial glucagon secretion, 3) impacts lipolysis and growth hormone secretion overnight, and 4) determine if TZP can maintain the glucagon response to hypoglycemia. The acute effects of TZP on metabolism will be assessed after 6 weeks, to limit the degree of weight loss (indicating a role for TZP on improving metabolic physiology in T1D, beyond weight management in T1D).

To address these research aims, a single comprehensive clinical trial will be performed in 44 participants with T1D, who will receive a weekly injection of TZP 2.5mg or placebo for 6 weeks. A short treatment duration was chosen to assess if TZP offers T1D-specific benefits prior to significant weight loss.

TIRTLE2 will employ the 'gold standard' hyperinsulinemic-euglycemic and hypoglycemic clamps, in conjunction with complementary analyses of the effects of TZP on metabolism across multiple physiological states. This mechanistic study will define mechanisms by which GLP1-GIP co-agonism may uniquely provide clinical benefits in T1D during the fasting and fed states, and during hypoglycemia.

Being tested
Tirzepatide 2.5mg weekly, Placebo injection (normal saline)
Keywords
Diabetes Mellitus, Type 1, Diabetes Mellitus, Autoimmune Diseases, Incretins, Physiological Effects of Drugs, Tirzepatide, Glucose Metabolism Disorders, Metabolic Diseases, Endocrine System Diseases, Overnutrition, Insulin Resistance
Medical subject headings
Diabetes Mellitus, Type 1, Diabetes Mellitus, Autoimmune Diseases, Glucose Metabolism Disorders, Metabolic Diseases, Endocrine System Diseases, Overnutrition, Insulin Resistance

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Tirzepatide 2.5mg weeklyDrug

    Tirzepatide 2.5 mg/0.5 mL solution for injection vial or pre-filled pen. Each vial/ pre-filled pen contains tirzepatide 2.5 mg in 0.5 mL solution (2.5mg in 0.6mL if Kwikpen)

    Tirzepatide will be administered by drawing up into a syringe, then administering by subcutaneous injection weekly by study nurses.

  • Placebo injection (normal saline)Drug

    Placebo will be given as 0.5mL normal saline (if comparator against vial or pre-filled pen), or 0.6mL (if comparator against Mounjaro Kwikpen), drawn up into a syringe and administered by subcutaneous injection weekly by study nurses.

Study groups in NCT06820281
Study groupRoleWhat they receive
Tirzepatide 2.5mg weeklyExperimentalAdministered subcutaneously.
Receives: Drug: Tirzepatide 2.5mg weekly
PlaceboPlacebo comparatorAdministered subcutaneously.
Receives: Drug: Placebo injection (normal saline)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Whole-body insulin sensitivity

    Change in insulin sensitivity from baseline, assessed using the hyperinsulinemic-euglycemic clamp (60 mU/m2/min)

    Measured: 6 weeks

Secondary outcomes (16)

  1. Prandial glucagon secretion

    Change from baseline glucagon area under the curve (AUC) during mixed meal tolerance test (MMTT)

    Measured: 6 weeks

  2. Glucagon response to hypoglycemia

    Change from baseline glucagon AUC after glucose nadir as measured during the hyperinsulinemic hypoglycemic clamp

    Measured: 6 weeks

  3. % Time level 2 hypoglycemia

    Change from baseline % time level 2 hypoglycemia (defined by glucose < 54 mg/dL [<3.0 mmol/L]) as measured by continuous glucose monitoring

    Measured: 6 weeks

  4. % Time level 1 hypoglycemia

    Change from baseline % time level 1 hypoglycemia (defined by glucose < 70 mg/dL [3.9 mmol/L] and ≥ 54 mg/dL [3.0 mmol/L]) as measured by continuous glucose monitoring

    Measured: 6 weeks

  5. Resting energy expenditure (REE)

    Change from baseline REE as measured by indirect calorimetry

    Measured: 6 weeks

  6. Overnight growth hormone curve

    Change from baseline growth hormone area under the curve (AUC) as measured overnight blood samples

    Measured: 6 weeks

  7. Overnight free-fatty acids (FFA) curve

    Change from baseline FFA under the curve (AUC) as measured overnight blood samples

    Measured: 6 weeks

  8. Total daily insulin dose

    Change from baseline total daily insulin dose as measured by pump record

    Measured: 6 weeks

  9. Total daily basal insulin dose

    Change from baseline total daily basal insulin dose as measured by pump record

    Measured: 6 weeks

  10. Total daily bolus insulin dose

    Change from baseline total daily bolus insulin dose as measured by pump record

    Measured: 6 weeks

  11. % Time in Range (TIR)

    Change from baseline %TIR (defined by % readings between 70mg/dL - 180 mg/dL [3.9 - 10.0 mmol/L]) as measured by continuous glucose monitoring

    Measured: 6 weeks

  12. % Time Below Range (TBR)

    Change from baseline %TBR (defined by % readings below 70mg/dL [3.9mmol/L]) as measured by continuous glucose monitoring

    Measured: 6 weeks

  13. % Time level 1 hyperglycemia

    Change from baseline % time level 1 hyperglycemia (defined by glucose > 180 mg/dL [10 mmol/L] and glucose ≤ 250 mg/dL [13.9 mmol/L]) as measured by continuous glucose monitoring

    Measured: 6 weeks

  14. % Time level 2 hyperglycemia

    Change from baseline % time level 1 hyperglycemia (defined by glucose > 250 mg/dL [13.9 mmol/L])) as measured by continuous glucose monitoring

    Measured: 6 weeks

  15. Glycemic variability

    Change from glycemic variability as measured by continuous glucose monitoring

    Measured: 6 weeks

  16. Gastric emptying

    Change from baseline gastric emptying during the mixed meal tolerance test (MMTT) assessed using radiolabelled isotope and breath sampling

    Measured: 6 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Feb 2025
  2. Study start7 Jul 2026
  3. Primary completion31 Dec 2027 (estimated)
  4. Study completion31 Dec 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Parallel assignment, 1:1 randomization
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
44 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06820281
Sponsor's protocol ID
U1111-1316-2752
Acronym
TIRTLE2
Status last verified
Sep 2026
First submitted
6 Feb 2025
Last updated
16 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Data from these analyses can be made available upon the condition of compliance with institutional review board restrictions and a data sharing agreement with the project sponsor. We encourage researchers who propose use of study data to contact the study PI.

Publications

  • Snaith JR, Frampton R, Samocha-Bonet D, Greenfield JR. Tirzepatide in Adults With Type 1 Diabetes: A Phase 2 Randomized Placebo-Controlled Clinical Trial. Diabetes Care. 2026 Jan 1;49(1):161-170. doi: 10.2337/dc25-2379.

    PubMed 41264593

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Tirzepatide 2.5mg weekly in people with Type 1 Diabetes Mellitus, run by Victor Chang Cardiac Research Institute at 1 site in Australia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 16 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Jennifer R Snaith, MD PHD (+61 2 9295 8600, j.snaith@victorchang.edu.au), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Whole-body insulin sensitivity (time frame: 6 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06820281, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Sep 2026.

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