Acute Metabolic Effects of Tirzepatide in Type 1 Diabetes

NCT ID: NCT06820281

Last Updated: 2025-10-08

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-12-01
• Study Completion Date: 2027-12-31

Brief 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 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.

Conditions

Type 1 Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Tirzepatide 2.5mg weekly

Administered subcutaneously.

Group Type: EXPERIMENTAL

Tirzepatide 2.5mg weekly

Intervention Type: DRUG

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

Administered subcutaneously.

Group Type: PLACEBO_COMPARATOR

Placebo injection (normal saline)

Intervention Type: 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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Garvan Institute of Medical Research

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jennifer R Snaith, MD PHD

Role: PRINCIPAL_INVESTIGATOR

Victor Chang Cardiac Research Institute

Jerry R Greenfield, MD PHD

Role: STUDY_DIRECTOR

Victor Chang Cardiac Research Institute

Locations

Garvan Institute of Medical Research

Sydney, New South Wales, Australia

Countries

Australia

Central Contacts

Jennifer R Snaith, MD PHD

Role: CONTACT

j.snaith@victorchang.edu.au

+61 2 9295 8600

Jerry R Greenfield, MD PHD

Role: CONTACT

j.greenfield@victorchang.edu.au

Facility Contacts

Jennifer R Snaith

Role: primary

j.snaith@garvan.org.au

61 2 9295 8100

Other Identifiers

U1111-1316-2752

Identifier Type: -

Identifier Source: org_study_id