TIRTLE1
Tirzepatide in Adults With Type 1 Diabetes: A Phase 2 Randomized Placebo-Controlled Clinical Trial
Snaith JR, Frampton R, Samocha-Bonet D, Greenfield JR · Diabetes Care
Study record
- Population
24 adults with type 1 diabetes for at least two years and BMI ≥30, randomized 12 per group; 22 completed, 11 per group. Ages 18–60 were eligible. Recent ketoacidosis or severe hypoglycemia and several major medical conditions were excluded.
Read source · Full-text reportResearch Design and Methods; Table 1- Formulation
Research staff administered tirzepatide or identical-appearing, volume-matched saline placebo. The retrieved protocol names Mounjaro, but exact preparation and device details remain unresolved in the sections inspected.
Inspect extraction gap · Full-text reportMethods — Intervention- Route
Subcutaneous study injections; usual insulin therapy continued with investigator-supported adjustment.
Read source · Full-text reportMethods — Intervention- Dose & frequency
Tirzepatide 2.5 mg once weekly for four weeks, then 5 mg for eight weeks; a lower dose was permitted for tolerability. Insulin adjustments depended on glucose response and clinical judgment, not a fixed percentage reduction.
Read source · Full-text reportMethods — Intervention- Study design
Single-site phase 2 trial, randomized 1:1 and masked to participants, outcome assessors and data analysts. Baseline-adjusted ANCOVA; the primary weight analysis used multiple imputation under missing-at-random assumptions. Secondary outcomes were not imputed, and confidence intervals were not multiplicity-adjusted.
Read source · Full-text reportMethods — Intervention and Statistical Analysis- Duration
12 weeks of treatment. This short study does not establish long-term use, discontinuation effects or repeatable cycles.
Read source · Full-text reportResearch Design and Methods- Reported findings
Adjusted weight difference was −8.7 kg versus placebo (95% CI −12.0 to −5.5). Total daily insulin geometric-mean ratio was 0.65 (95% CI 0.53–0.79); this is an observed trial comparison, not a recommended dose reduction. No significant time-in-range difference was found. Pulse increased by 7.7 beats/min relative to placebo (95% CI 2.1–13.3).
Read source · Full-text reportTable 2; Methods — Statistical Analysis- Adverse events
Table S2 reports 14 nonserious events affecting 9/12 tirzepatide participants versus one event affecting 1/12 placebo participants. No serious events, severe hypoglycemia or ketoacidosis were reported. Listed symptoms include nausea, vomiting, diarrhea, reflux and constipation; depression and anxiety were considered possibly related, with one discontinuation. Gastroenteritis overlapped gastrointestinal symptom reporting, so the rows should not be added as independent events. This small, short trial cannot establish broad safety.
Read source · Full-text reportSupplementary appendix, Table S2 and footnotes, PDF page 9- Monitoring
Participants received education about insulin requirements, hypoglycemia and ketone risk; glucagon access was confirmed. Phone follow-up followed the first two doses after initiation and escalation, with additional study-team contact available. Blinded investigators supported insulin adjustment using glucose response.
Read source · Full-text reportMethods — Intervention
What it supports
Demonstrates short-term weight reduction when tirzepatide was added to insulin with study-team support in selected adults with type 1 diabetes and obesity.
What it does not establish
Insulin continued throughout; this is not insulin-replacement evidence. Primary weight results used 12 participants per group with imputation, while secondary outcomes generally used 11 per group. Small sample, short follow-up and unadjusted secondary comparisons limit certainty. Fat-free mass difference was −1.8 kg (95% CI −3.8 to 0.1), which does not prove absence of lean-mass loss. Table 1 and Figure 2 disagree on pump-user counts; the retrieved supplement has not yet resolved that discrepancy. Supplementary diet estimates contain unresolved confidence-interval inconsistencies. Satisfaction results come from eight respondents per group and do not establish cardiovascular protection. The supplied analysis plan is dated February 2025, after the reported May–December 2024 trial period; an amendment added the satisfaction survey during the trial. This does not establish that every analysis was specified before recruitment.
Funding
Sponsored by the Garvan Institute of Medical Research. Project funding: St. Vincent’s Clinic Foundation, Australian Diabetes Society Lindsey Baudinet Rising Star Award in Type 1 Diabetes Research, and Melissa and Jonathon Green; additional author support is disclosed in the report.
Literature search cutoff: 2026-09-08 · Not independently clinically reviewed
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