TIRTLE1 low-dose tirzepatide in adults with T1D and obesity
What this study tests
Completed Australian phase-2 trial of weekly tirzepatide versus placebo alongside insulin in adults with T1D and obesity. Twenty-four were randomized and 22 completed 12 weeks. Weight fell, but time in range did not improve significantly; uncommon and long-term harms remain uncertain.
Editorial review: .
Registry checked: 2026-09-17. Registry’s own update: 2025-04-27.
Most recent recorded citation date: 2025-11-20. Only explicit date metadata is included; an undated citation may be newer. This does not mean every claim was reviewed on that date.
Trial status, labels and access can change between reviews. How we review the evidence · How to read the evidence
Evidence at a glance
- Who can enter the study?
- Adults aged 18-60 with T1D for at least two years and BMI at least 30 kg/m2. Exclusions included DKA or severe hypoglycemia within three months, gastroparesis, pancreatitis, proliferative retinopathy or macular edema, and pregnancy or breastfeeding. See the registry and paper for complete criteria. Registered eligibility ↗Enrollment criteria describe who may enter. They do not establish who was analyzed or the denominator for a reported result.
- Reported benefit and results
- The primary weight analysis included all 24 randomized participants with imputation; secondary analyses used 22 completers. At 12 weeks, the baseline-adjusted weight difference was −8.7 kg (95% CI −12.0 to −5.5; P<0.0001), described as an 8.8% placebo-adjusted reduction. Total daily insulin requirements were approximately 35% lower relative to placebo (adjusted geometric-mean ratio 0.65; 95% CI 0.53–0.79). HbA1c differed by −0.4 percentage points (95% CI −0.7 to 0.0; P=0.05); time in range differed by +8.4 points (95% CI −4.0 to 20.9; P=0.17), not significant. Time below range also did not differ significantly. No DKA, severe hypoglycemia or serious adverse events were reported. Nonserious events affected 9/12 versus 1/12 participants. The supplement lists possibly related depression and anxiety events and one discontinuation; the main paper associates the anxiety withdrawal with preexisting history and weekly facility-visit demands. The study was powered for weight and did not adjust secondary confidence intervals for multiple comparisons.Read the result sources and their limitations →
- Important harms
- Read the reported results, safety discussion and original sources. A separate harms summary is not available; this does not establish safety.
- Research access and approval
- Study regions: Australia. A trial listing does not establish product approval or current recruitment at a particular site. Check the study’s current entry requirements.
- What remains uncertain?
- Read the full discussion and original sources for study limitations. Planned endpoints and completion dates are not results.
Research status alone does not establish approval, clinical benefit or local availability. This record cites company or conference reports. Those sources may describe interim findings; their source type is shown in the source list.
Primary endpoints
- Change in body weight at 12 weeks
The full picture
The ANZCTR record lists this study as completed, with actual first enrollment on 14 May 2024, last enrollment on 1 August 2024 and last data collection on 31 December 2024. The registry's final enrollment of 24 differs from the paper's 22 completers: 12 were randomized per arm and 11 per arm completed. The trial took place in Australia; the registry lists New South Wales.123
The published protocol used a 12-week treatment period, with weekly facility visits and study-team insulin support. Its selected population excluded several higher-risk conditions. The paper reports preexisting symptoms/history around the depression and anxiety events; the supplement classifies them as possibly related, which does not establish causation. Zero serious events in this small trial do not establish uncommon-event safety. The insulin result is a group-level trial estimate, not an individual dose-adjustment rule.23
This trial investigates adjunctive treatment in T1D; it does not establish a licensed T1D glucose-control indication. The August 2026 US Zepbound label separately covers adult obesity, or overweight with a weight-related condition. An eligible adult with T1D may meet that obesity indication; trial enrollment criteria and obesity prescribing eligibility are different.4
Sources
- [1]Tirzepatide in Type 1 Diabetes — Cardiometabolic Effects (TIRTLE) · Trial registry · 2025-04-27 — ANZCTR checked 17 September 2026: prospectively registered 8 February 2024, last updated 27 April 2025, completed. Actual first enrollment 14 May 2024, last enrollment 1 August 2024 and last data collection 31 December 2024; final enrollment 24, not 24 completers.
ANZCTR ACTRN12624000111572, registration, eligibility and recruitment sections; checked 17 September 2026.
- [2]Tirzepatide in Adults With Type 1 Diabetes: A Phase 2 Randomized Placebo-Controlled Clinical Trial · Peer-reviewed study · 2025-11-20 — Snaith et al., Diabetes Care 2026;49:161-170. Reports the prospectively registered, double-blind trial conducted May-December 2024, with 24 randomized and 22 completing 12 weeks.
Snaith et al., original full trial report, Methods, Table 2 and Safety and Tolerability. Online 20 November 2025; January 2026 issue.
- [3]TIRTLE1 supplementary appendix: participant flow and safety · Peer-reviewed study — Figure S1 (page 6): 12 randomized per arm and 11 completers per arm. Table S2 (page 9): 14 versus 1 nonserious events in 9 versus 1 participants; possibly related depression/anxiety and one discontinuation.
Original supplementary appendix, Figure S1 and Table S2.
- [4]Zepbound US prescribing information, revised August 2026 · Manufacturer — Section 1 covers adult obesity/overweight weight management and obstructive sleep apnea in adults with obesity; these are separate from the investigational T1D glycemic use studied here.
Zepbound US prescribing information, revised August 2026, section 1.