Tirzepatide produced significant weight loss, reduced insulin requirements, and improved glucose control without increasing hypoglycemia when used off-label in adults with type 1 diabetes (T1D), new observational data showed.

The findings, from a retrospective study of 57 adults with T1D and obesity, will be presented on September 16, 2025, in a poster at the European Association for the Study of Diabetes (EASD) Annual Meeting by Ahmed Iqbal, MBBS, senior clinical lecturer in diabetes and honorary consultant physician in diabetes and Simon Berry, MBChB, clinical research fellow in diabetes, both of the University of Sheffield and Sheffield Teaching Hospitals NHS Foundation Trust in Sheffield, England, and colleagues.

“Insulin resistance is problematic in the management of T1D, making it even harder for people with type 1 diabetes to match insulin accurately to carbohydrates and activity. The exact mechanisms of tirzepatide in T1D have not yet been established but we believe that there is both a direct effect on insulin sensitivity and an indirect effect through weight loss,” Berry and Iqbal told Medscape Medical News in an email.

They added that addressing cardiovascular risk in people with T1D and insulin resistance is an “urgent unmet need,” including addressing risk factors such as hypertension, microalbuminuria, and dyslipidemia with standard care. “The goal of treatment in our patients was to reduce insulin resistance and address cardiovascular risk factors rather than solely focusing on BMI,” they said.

There are currently no professional recommendations for the use of GLP-1 receptor agonist (RA)-based medication in T1D, and its use isn’t licensed for that patient population. However, electronic health data show that off-label use is common. “Fully powered randomized controlled trials [RCTs] are required to give us definitive data to inform future prescribing but at present, we believe tirzepatide should be considered on a case-by-case basis, particularly in those with problematic insulin resistance,” Berry and Iqbal noted.

Eli Lilly is conducting a large RCT of tirzepatide in people with T1D and obesity, with results expected in 2027. But, prior to that, results from the first RCT of tirzepatide in T1D will also be presented at the EASD meeting. Those data aren’t being released early, but the results are along the same lines, lead author, Jerry Greenfield, MD, told Medscape Medical News.

Greenfield, who is head of the Department of Endocrinology, director of Diabetes Services, at St Vincent’s Hospital, Sydney, Australia, said that the UK study and findings “are impressive and very similar to what has been reported in previous retrospective studies. It’s not an RCT, but nonetheless, the data do reflect real world practice in so in many respects, so they’re very informative.”

Tirzepatide Benefits in T1D Seen at 6 Months

Berry, Iqbal, and colleagues included 57 adults with T1D who had been started on tirzepatide at Sheffield Teaching Hospitals. The principal goal of therapy in all patients was to improve glycemia by addressing insulin resistance in those with obesity and T1D, with weight loss seen as an added benefit.

Prior to starting tirzepatide, the 57 had a mean age of 39 years, diabetes duration 20 years, BMI 36.3, and A1c 7.7%. At 6 months, the once weekly tirzepatide doses were 2.5 mg in nine participants (18%), 5 mg in 37 (74%), 7.5 mg in two, and one each taking 10 mg and 15 mg.

At 6 months, the mean weight reduction among the 42 participants who remained in the study was 9.8 kg (9.3%; P < .001). The mean insulin dose reduction was 25.2%, from 74.4 to 57.3 units per day (P < .001).

The mean A1c decreased from 61 mmol/mol (7.7%) at baseline to 57.3 mmol/mol (7.3%), a significant drop (0.4 percentage points; P = .008). Time in range (3.9-10.00 mmol/mol, 70-180mg/dL) rose from 55.1% at baseline to 62.3% at 6 months (P = .022), with a corresponding drop in time above range and no difference in time below range (1.1% both time points). There was no significant correlation between percentage weight change and increase in time in range.

Side effects were reported by 21 participants (36.8%), most commonly nausea/vomiting (26.3%, n = 15) and abdominal pain (14.0%, n = 8) but only seven participants (12.3%) discontinued taking tirzepatide due to side effects. There were three unplanned hospital admissions for abdominal pain related to tirzepatide, although gallstones were found in one. There were no cases of pancreatitis.

Greenfield, who is also professor of medicine at the University of New South Wales, Sydney, Australia, told Medscape Medical News that there is no physiological reason why the GLP-1 RAs should not be effective in T1D, but that safety needs to be established, particularly regarding hypoglycemia and diabetic ketoacidosis. “That’s where the major hurdle will be in getting these drugs approved for T1D.” 

In the meantime, he advised that clinicians be prepared to discuss this, given that increasing numbers of patients with T1D are asking for the drugs. “I think this is the way of the future, that people with T1D will be on insulin plus an adjunct. The question is which one. We look forward to reporting our RCT of tirzepatide in type 1 because obviously that is the best level of evidence.”

Berry declared no conflict of interest related to this study. Iqbal and another senior author reported receiving speaker fees from Eli Lilly. Greenfield reported receiving study drug and placebo from Novo Nordisk, but not Eli Lilly.

Miriam E. Tucker is a freelance journalist based in the Washington, DC, area. She is a regular contributor to Medscape, with other work appearing in the Washington Post, NPR’s Shots blog, and Diatribe. She is on X @MiriamETucker and BlueSky @miriametucker.bsky.social.