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Not yet recruiting NCT06820281

Acute Metabolic Effects of Tirzepatide in Type 1 Diabetes

Phase II Interventional Type 1 Diabetes Mellitus

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: Tirzepatide 2.5mg weekly, Placebo injection (normal saline).
Who it may be relevant to
Registry conditions: Type 1 Diabetes Mellitus. Basic parameters: 18 years — 65 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
Australia
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Official title

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

Overview

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.

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.

Interventions

  • Drug Tirzepatide 2.5mg weekly
    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.
  • Drug Placebo injection (normal saline)
    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.

Primary outcome measures

  • Whole-body insulin sensitivity [Time frame: 6 weeks]
Secondary outcome measures (12)
  • Prandial glucagon secretion [Time frame: 6 weeks]
  • Glucagon response to hypoglycemia [Time frame: 6 weeks]
  • % Time level 2 hypoglycemia [Time frame: 6 weeks]
  • % Time level 1 hypoglycemia [Time frame: 6 weeks]
  • Resting energy expenditure (REE) [Time frame: 6 weeks]
  • Overnight growth hormone curve [Time frame: 6 weeks]
  • Overnight free-fatty acids (FFA) curve [Time frame: 6 weeks]
  • Total daily insulin dose [Time frame: 6 weeks]
  • Total daily basal insulin dose [Time frame: 6 weeks]
  • Total daily bolus insulin dose [Time frame: 6 weeks]
  • % Time in Range (TIR) [Time frame: 6 weeks]
  • % Time Below Range (TBR) [Time frame: 6 weeks]

Eligibility criteria

Inclusion criteria

  • age 18-65 years
  • BMI ≥ 27 kg/m2
  • HbA1c ≤ 9.0%
  • insulin delivery using an automated insulin delivery system
  • at least 2 years since diagnosis of type 1 diabetes

Exclusion criteria

  • TZP or GLP-1 receptor agonist in last 3 months; metformin or sodium glucose co-transporter 2 (SGLT2) inhibitor in the last 6 weeks; steroids, antipsychotics, immunosuppressants 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).
  • Active malignancy.
  • Pregnant, breastfeeding, planning pregnancy within 6 months, or not using adequate contraception.
  • History of cardiovascular disease, or coronary event or stroke in last 3 months
  • Hemoglobin level < 13.5 g/dL in men, < 12.0 g/dL in women

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation
Randomized
Model
Parallel assignment
Masking
Quadruple blind
Primary purpose
Treatment

Study locations

Australia · 1 center
  • Victor Chang Cardiac Research Institute — Sydney

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. PMID 41264593

Identifiers

NCT: NCT06820281 · U1111-1316-2752

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗