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Acute Metabolic Effects of Tirzepatide in Type 1 Diabetes

PHASE2RECRUITING

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.

Study details:

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.

Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

Inclusion criteria

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

Exclusion criteria

  1. 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.
  2. Hypoglycemic unawareness or severe hypoglycemia last 6 months.
  3. History of seizure disorder.
  4. History of weight loss surgery.
  5. eGFR <60 mL/min/1.73 m2.
  6. Liver disease (known cirrhosis, LFTs > 3x upper limit of normal).
  7. Active malignancy.
  8. Pregnant, breastfeeding, planning pregnancy within 6 months, or not using adequate contraception.
  9. History of cardiovascular disease, or coronary event or stroke in last 3 months
  10. Hemoglobin level < 13.5 g/dL in men, < 12.0 g/dL in women

Eligibility

Age eligible for study : NA

Healthy volunteers accepted : No

Gender eligible for study: ALL

Things to know

Study dates

Study start:

Primary completion:

Study completion finish:

study type

Study type

TREATMENT

phase

Phase

    PHASE2

trial

Study ID

NCT06820281

Intervention or treatment

DRUG: Tirzepatide 2.5mg weekly

DRUG: Placebo injection (normal saline)

Conditions

  • Type 1 Diabetes Mellitus

  • Condition: Type 1 Diabetes Mellitus

  • DRUG: Tirzepatide 2.5mg weekly and other drugs

  • Sydney, New South Wales, Australia

  • Sponsor: Garvan Institute of Medical Research

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Research sites nearby

Closest Location:

Garvan Institute of Medical Research

Select from list below to view details:

  • Garvan Institute of Medical Research

    Sydney, New South Wales, Australia

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Who is running the clinical trial?

GIoMR

Garvan Institute of Medical Research

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Participant Group/ArmIntervention/Treatment
EXPERIMENTAL: Tirzepatide 2.5mg weekly
  • Administered subcutaneously.
Drug: Tirzepatide 2.5mg weekly
    PLACEBO_COMPARATOR: Placebo
    • Administered subcutaneously.
    Drug: Placebo injection (normal saline)

      What is the study measuring?

      Primary Outcome

      MeasureDescriptionTime Frame
      Whole-body insulin sensitivityChange in insulin sensitivity from baseline, assessed using the hyperinsulinemic-euglycemic clamp (60 mU/m2/min)6 weeks

      Secondary Outcome

      MeasureDescriptionTime Frame
      Prandial glucagon secretionChange from baseline glucagon area under the curve (AUC) during mixed meal tolerance test (MMTT)6 weeks
      Glucagon response to hypoglycemiaChange from baseline glucagon AUC after glucose nadir as measured during the hyperinsulinemic hypoglycemic clamp6 weeks
      % Time level 2 hypoglycemiaChange from baseline % time level 2 hypoglycemia (defined by glucose \< 54 mg/dL \[\<3.0 mmol/L\]) as measured by continuous glucose monitoring6 weeks
      % Time level 1 hypoglycemiaChange 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 monitoring6 weeks
      Resting energy expenditure (REE)Change from baseline REE as measured by indirect calorimetry6 weeks
      Overnight growth hormone curveChange from baseline growth hormone area under the curve (AUC) as measured overnight blood samples6 weeks
      Overnight free-fatty acids (FFA) curveChange from baseline FFA under the curve (AUC) as measured overnight blood samples6 weeks
      Total daily insulin doseChange from baseline total daily insulin dose as measured by pump record6 weeks
      Total daily basal insulin doseChange from baseline total daily basal insulin dose as measured by pump record6 weeks
      Total daily bolus insulin doseChange from baseline total daily bolus insulin dose as measured by pump record6 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 monitoring6 weeks
      % Time Below Range (TBR)Change from baseline %TBR (defined by % readings below 70mg/dL \[3.9mmol/L\]) as measured by continuous glucose monitoring6 weeks
      % Time level 1 hyperglycemiaChange 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 monitoring6 weeks
      % Time level 2 hyperglycemiaChange from baseline % time level 1 hyperglycemia (defined by glucose \> 250 mg/dL \[13.9 mmol/L\])) as measured by continuous glucose monitoring6 weeks
      Glycemic variabilityChange from glycemic variability as measured by continuous glucose monitoring6 weeks
      Gastric emptyingChange from baseline gastric emptying during the mixed meal tolerance test (MMTT) assessed using radiolabelled isotope and breath sampling6 weeks
      Are you running this trial?If you're a clinic or sponsor, you can claim this study.
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      References

      Clinical Trials Gov: Acute Metabolic Effects of Tirzepatide in Type 1 Diabetes

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