Acute Metabolic Effects of Tirzepatide in Type 1 Diabetes

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат 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.
• Препарат 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.

Первичные конечные точки

• Whole-body insulin sensitivity [Срок оценки: 6 weeks]

Вторичные конечные точки (12)

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

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Австралия · 1 центр

• Victor Chang Cardiac Research Institute — Sydney

Публикации

• 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

Идентификаторы

NCT: NCT06820281 · U1111-1316-2752

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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