TIRTLE1 published: the first randomized trial of tirzepatide in type 1 diabetes

A phase 2 trial known as TIRTLE1 has become the first randomized, placebo-controlled study of tirzepatide in adults with type 1 diabetes, and the results were published this month in Diabetes Care ^[1]. The 12-week trial enrolled 24 adults with type 1 diabetes and a body mass index above 30, randomizing them to low-dose tirzepatide or placebo ^[1]. Tirzepatide, sold as Mounjaro and Zepbound for other conditions, has not previously been tested in people with type 1 diabetes because they were excluded from the drug's original approval studies ^[2].

Participants on tirzepatide received 2.5 mg weekly for four weeks, then 5 mg weekly for eight weeks, doses lower than those typically used for weight loss or type 2 diabetes ^[1]. Of the 24 people enrolled, 22 completed the study ^[1]. Average weight loss was 10.3 kg in the tirzepatide group compared with 0.7 kg on placebo, a treatment difference of 8.7 kg, or about 8.8% of body weight ^[1]. Every person on tirzepatide lost at least 5% of their body weight, compared with 9% of those on placebo, and 45% of the tirzepatide group lost 10% or more, versus none on placebo ^[1].

Blood sugar control also improved. HbA1c, a measure of average blood sugar over about three months, fell 0.4 percentage points more on tirzepatide than placebo, a result researchers describe as at the edge of statistical significance ^[1]. Total daily insulin dose dropped by 24.2 units per day in the tirzepatide group compared with a 0.3 unit drop on placebo, amounting to a 35% relative reduction ^[1]. The study authors reported no significant adverse events in either group during the 12 weeks ^[1].

A separate systematic review published in 2026 looked at this trial alongside seven observational studies of tirzepatide added to insulin in adults with type 1 diabetes ^[2]. The review's authors said body weight reduction was the most consistent finding across studies, but they rated the overall certainty of evidence as low to very low, citing the small size of the randomized trial and serious risk of bias in most of the observational data ^[2]. They also noted that gastrointestinal side effects were the most common safety issue reported across the broader evidence base, even though the randomized trial itself did not report significant adverse events ^[2].

Why it matters for patients

Type 1 diabetes was once seen as a condition affecting mostly lean people, but excess weight has become common among adults living with it, and extra weight is linked to higher insulin resistance and greater cardiovascular risk ^[2]. Because people with type 1 diabetes were left out of the trials that led to tirzepatide's approval, this drug is not currently approved for that use, and TIRTLE1's results come from a study designed to test safety and short-term effects, not to establish a new use ^{[1] [2]}. The size of the weight and insulin-dose changes may be of interest to patients and doctors managing type 1 diabetes and obesity together, but the review's low-certainty rating reflects real limits: 12 weeks is short, the sample was small, and most other evidence is observational and prone to bias ^{[1] [2]}.

What happens next

The systematic review's authors say larger, dedicated randomized trials are needed to establish durable glucose benefits and long-term safety ^[2]. Two sponsor-led trials, listed in public registries as NCT06914895 and NCT06962280, are already underway to test tirzepatide in type 1 diabetes on a larger scale ^[2].