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.
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
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).
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- 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.
Jerry R Greenfield, MD PHD contact
Australia1 site, 1 recruiting
- 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
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.
- Conditions
- Type 1 Diabetes Mellitus
- 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 group | Role | What they receive |
|---|---|---|
| Tirzepatide 2.5mg weekly | Experimental | Administered subcutaneously. Receives: Drug: Tirzepatide 2.5mg weekly |
| Placebo | Placebo comparator | Administered subcutaneously. Receives: Drug: Placebo injection (normal saline) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Prandial glucagon secretion
Change from baseline glucagon area under the curve (AUC) during mixed meal tolerance test (MMTT)
Measured: 6 weeks
Glucagon response to hypoglycemia
Change from baseline glucagon AUC after glucose nadir as measured during the hyperinsulinemic hypoglycemic clamp
Measured: 6 weeks
% 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
% 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
Resting energy expenditure (REE)
Change from baseline REE as measured by indirect calorimetry
Measured: 6 weeks
Overnight growth hormone curve
Change from baseline growth hormone area under the curve (AUC) as measured overnight blood samples
Measured: 6 weeks
Overnight free-fatty acids (FFA) curve
Change from baseline FFA under the curve (AUC) as measured overnight blood samples
Measured: 6 weeks
Total daily insulin dose
Change from baseline total daily insulin dose as measured by pump record
Measured: 6 weeks
Total daily basal insulin dose
Change from baseline total daily basal insulin dose as measured by pump record
Measured: 6 weeks
Total daily bolus insulin dose
Change from baseline total daily bolus insulin dose as measured by pump record
Measured: 6 weeks
% 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
% 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
% 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
% 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
Glycemic variability
Change from glycemic variability as measured by continuous glucose monitoring
Measured: 6 weeks
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.
- First posted11 Feb 2025
- Study start7 Jul 2026
- Primary completion31 Dec 2027 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Type 1 Diabetes MellitusStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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)
Sponsor and investigators
- Lead sponsor
- Victor Chang Cardiac Research Institute
- Sponsor type
- Other government
- Responsible party
- Sponsor
- Investigators
- Jennifer R Snaith, MD PHD, Principal investigator, Victor Chang Cardiac Research InstituteJerry R Greenfield, MD PHD, Study director, Victor Chang Cardiac Research Institute
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