Off-label in type 1 diabetes, tirzepatide brought more low blood sugar reports

Neither tirzepatide nor semaglutide is approved for type 1 diabetes, but both are increasingly used off-label alongside insulin in adults with type 1 diabetes who are overweight or obese, for their effects on glucose control, weight, and insulin dose. A study published this month in Diabetes Technology & Therapeutics is among the first to systematically document adverse events specifically in this off-label population [s1].

The design

Researchers at the Barbara Davis Center for Diabetes surveyed 230 adults with type 1 diabetes who were using tirzepatide or semaglutide as an add-on to insulin therapy, collecting demographics, diabetes control metrics, details of drug use, and related adverse events at a single center [s1].

What it found

Male participants using either drug had a higher baseline body weight than female participants — 107.8 kg versus 89.6 kg (p < 0.01) — and were older on average, 44.2 years versus 40.4 years (p < 0.05) [s1].

The central finding: symptomatic hypoglycemia was reported by 29% of participants on tirzepatide compared with 13.4% on semaglutide (p < 0.001) — roughly double the rate [s1]. Gastrointestinal adverse events, the side effects most familiar from these drugs' use in type 2 diabetes and obesity, did not differ meaningfully between the two drugs in this survey, though younger adults and women were more likely to report them regardless of which drug they were on [s1]. The proportion of people who reduced their dose because of adverse events was similar between the tirzepatide and semaglutide groups [s1].

Why hypoglycemia risk is different in type 1 diabetes

The finding matters specifically because of what makes type 1 diabetes different from type 2: people with type 1 diabetes have no functioning insulin production of their own and rely entirely on injected or pumped insulin, dosed to match food and activity. A drug that improves insulin sensitivity or reduces insulin requirements, without a corresponding downward adjustment of insulin dose, can push blood sugar low. GLP-1 and dual GIP/GLP-1 drugs are not typically thought of as hypoglycemia risks on their own — in people without diabetes or with type 2 diabetes not on insulin, they rarely cause it — but layered onto exogenous insulin dosing in type 1 diabetes, the researchers' data suggests that risk becomes real, and more pronounced with tirzepatide than semaglutide in this sample [s1].

Reading the limits

This is a patient-reported, single-center survey of 230 people, not a randomized comparison — participants weren't assigned to tirzepatide or semaglutide, so any difference in who chose or was prescribed each drug (dose, insulin regimen, baseline control) could contribute to the hypoglycemia difference rather than the drugs alone. "Symptomatic hypoglycemia" as self-reported by survey is a softer endpoint than a continuous glucose monitor-confirmed low blood sugar event, and the study doesn't report the severity or frequency of episodes, only the proportion of people reporting them at least once. Both drugs remain off-label for type 1 diabetes; nothing in the study changes that regulatory status.

What the authors recommend

The study's authors call for individualized risk assessment and close monitoring of insulin dose changes when prescribing either drug off-label in adults with type 1 diabetes [s1] — a recommendation aimed at clinicians already prescribing these drugs in this population, not a suggestion that patients change medication or insulin doses on their own.

What to watch

Larger, ideally prospective studies using continuous glucose monitoring data rather than self-report, and clarity on whether the hypoglycemia difference tracks with dose, insulin regimen, or something else about how the two drugs are used in type 1 diabetes. This article describes off-label drug use and adverse event data; it is not medical advice, and changes to insulin or GLP-1 dosing in type 1 diabetes should not be made without a treating clinician.

Sources

1. Patient-Reported Adverse Events with Adjunctive Tirzepatide or Semaglutide Treatment in Adults with Type 1 Diabetes — Diabetes Technology & Therapeutics, 10 March 2026