Tirzepatide as an adjunct in T1D
Eli Lilly and Company
Promising for obesity in T1D, not yet a licensed T1D therapy.
A weekly dual GIP/GLP-1 agonist being tested alongside insulin in adults with T1D and overweight or obesity. A 24-person randomized phase-2 trial found striking short-term weight and insulin-dose reductions, but no significant time-in-range improvement; large phase-3 trials are now underway. Tirzepatide is marketed for type 2 diabetes and obesity, not approved as a T1D treatment.
The scorecard
In TIRTLE1 the placebo-adjusted HbA1c difference was 0.4 percentage points at the statistical boundary (P=0.05), while time in range and time below range did not differ significantly. The phase-3 programme is needed to establish the glycemic effect.[1]
No diabetic ketoacidosis, severe hypoglycemia, or serious adverse events occurred in the 24-person, 12-week trial. But nonserious adverse events occurred in 75% on tirzepatide versus 8.3% on placebo, mostly gastrointestinal, and the sample is far too small to define rare harms.[1]
The phase-2 signal was large: an 8.8% placebo-adjusted weight reduction and a 35.1% relative reduction in total daily insulin dose over 12 weeks. No cardiovascular or kidney outcome benefit has been demonstrated in T1D.[1]
The T1D evidence includes one very small randomized phase-2 trial, but two Lilly phase-3 studies now enroll a combined planned 1,370 adults. The pivotal 905-person study has completed enrollment, with primary completion estimated in November 2026.[2]
Tirzepatide is marketed for other indications and is used off-label in some people with T1D, but no regulator has approved it as a T1D adjunct. Coverage, dosing, and liability therefore differ from licensed care.[2]
These are scored as add-ons to insulin in Type 1 diabetes, never on their Type 2 diabetes evidence — a drug with a large Type 2 trial base but only small Type 1 studies scores low on maturity. Safety carries heavy weight here because the best-known adjunct risk, diabetic ketoacidosis at normal glucose levels, is potentially fatal and specific to Type 1. Most of this class is used off-label; that is reflected in access, not hidden.
Editor’s take
The early signal is too large to ignore and too small to trust without phase 3. TIRTLE1 was 24 people for 12 weeks: excellent evidence that weight and insulin needs can move quickly, weak evidence about durable glucose benefit or uncommon harm. The right use-case is T1D plus obesity or insulin resistance, not replacing insulin and not relabelling type-2 evidence as type-1 evidence.
The full picture
Tirzepatide activates both the GIP and GLP-1 receptors. It is sold for type 2 diabetes and obesity, but those approvals do not cover type 1 diabetes. In T1D it is being studied alongside insulin, mainly for adults who also have overweight, obesity, or high insulin requirements.
The first randomized T1D result
TIRTLE1 randomized 24 adults with T1D and obesity to low-dose tirzepatide or placebo for 12 weeks; 22 completed the study. Weight fell 10.3 kg with tirzepatide and 0.7 kg with placebo, an adjusted difference of 8.7 kg or 8.8% of body weight. Total daily insulin dose fell by about 35% relative to placebo.1
The glucose result was less decisive. HbA1c improved by 0.4 percentage points versus placebo, with P=0.05, while continuous-glucose time in range did not change significantly. This was a weight-loss trial, not a definitive glycemic trial, and the confidence intervals were not adjusted for multiple secondary comparisons.1
No participant had diabetic ketoacidosis, severe hypoglycemia, or a serious adverse event, but nonserious events occurred in 75% of the tirzepatide group and 8.3% of placebo, most often gastrointestinal symptoms. That is reassuring for 12 weeks and 24 people, not a rare-event safety database.
What phase 3 is testing
Lilly's SURPASS-T1D-1 study plans 905 adults with T1D and overweight or obesity. The sponsor says enrollment is complete; the registry lists it active but not recruiting, with primary completion estimated in November 2026.2 A 465-person longer-term companion study follows through July 2027.3 Other investigator studies are testing tirzepatide with automated insulin delivery, including whether it can reduce the burden of meal announcements.
Until those results and a regulatory decision arrive, tirzepatide remains an off-label adjunct in T1D. Its rapid reduction in food intake and insulin need is also why this is not a drug to layer onto an unchanged insulin plan casually; insulin remains life-sustaining, and the phase-2 study included active insulin adjustment and ketone-safety support.
References
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Snaith JR, et al. Tirzepatide in Adults With Type 1 Diabetes: A Phase 2 Randomized Placebo-Controlled Clinical Trial. Diabetes Care (2026 issue; published online 20 November 2025). https://doi.org/10.2337/dc25-2379 ↩ ↩2
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Eli Lilly. SURPASS-T1D-1 (NCT06914895). https://trials.lilly.com/en-US/trial/589916 ↩
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ClinicalTrials.gov. Long-term tirzepatide safety and efficacy in adults with T1D and obesity or overweight (NCT06962280). https://clinicaltrials.gov/study/NCT06962280 ↩
Coming soon
ETA · SURPASS-T1D-1 primary completion is estimated in November 2026, with study completion in December; SURPASS-T1D-2 follows participants through July 2027.
- →SURPASS-T1D-1 phase-3 HbA1c, weight, insulin-dose, and safety results · primary completion estimated November 2026
- →SURPASS-T1D-2 longer-term phase-3 results · study completion estimated July 2027
- →Investigator trials pairing tirzepatide with automated insulin delivery, including reduced meal-announcement strategies · recruiting
Sources
- [1]Tirzepatide in Adults With Type 1 Diabetes: A Phase 2 Randomized Placebo-Controlled Clinical Trial · peer-reviewed · 2025-11-20 — Twenty-four adults with T1D and obesity were randomized and 22 completed 12 weeks. The study was powered for weight, not glycemic or safety outcomes; its journal issue is Diabetes Care 2026;49:161-170.
- [2]SURPASS-T1D-1: tirzepatide versus placebo in adults with T1D and obesity or overweight · manufacturer — Lilly lists phase 3, enrollment goal 905, trial dates 25 April 2025 to December 2026, and status COMPLETED ENROLLMENT. ClinicalTrials.gov NCT06914895 remains ACTIVE_NOT_RECRUITING.
- [3]Long-term tirzepatide safety and efficacy in adults with T1D and obesity or overweight · registry · 2026-02-17 — ACTIVE_NOT_RECRUITING phase 3; estimated n=465; primary completion November 2026 and full completion July 2027.