The TIRTLE 2 clinical trial is investigating whether a weekly injection of an existing drug called tirzepatide can help people with type 1 diabetes (T1D) keep their blood glucose in a healthy range and limit their risk of T1D complications.
The challenge of meeting target time in range
Despite science breakthroughs that help to relieve some of the burden of managing type 1 diabetes (T1D), including continuous glucose monitors (CGMs) and faster acting insulins, most people living with T1D don’t meet their target time in range.
Over time, having repeated high blood glucose (hyperglycaemia) can cause damage to other organs in the body, such as the kidneys, heart and eyes. This is known as the long-term complications of T1D. Meanwhile, extreme lows in blood glucose (hypoglycaemia) can be very dangerous, and even fatal.
The glucagon response
The hormone glucagon is normally released when blood levels fall too low and triggers the release of glucose stored in the liver into the blood, raising blood glucose levels. But people with T1D may have an impaired glucagon response, with too much glucagon being released after meals and overnight, and not enough released when blood glucose is too low. This increases the risk of both severe hypos and prolonged hypers.
Insulin resistance
Another challenge people with T1D face is insulin resistance, where cells don’t respond as well to insulin. This can lead to people requiring more insulin to try and stay in range, which can further increase the risk of complications. Increased insulin resistance (reduced insulin sensitivity) is associated with increased risk of cardiovascular (heart and blood vessels) complications of T1D and contributes to difficulties in managing blood glucose levels and weight.
Overall, there is a large unmet need for treatments that help reduce insulin resistance and lower blood glucose levels without causing hypos to help prevent long- and short-term complications of T1D.
Could tirzepatide be the answer?
This project will determine if tirzepatide can tackle this challenge by improving insulin sensitivity and restoring the normal glucagon response. Tirzepatide mimics the action of hormones naturally released when we eat that slows movement of food through the gut, decreasing appetite and reducing hunger.
It also helps lower blood glucose levels by suppressing glucagon release, helping glucose move out of the bloodstream into body tissue, which can improve insulin sensitivity.Â
Tirzepatide is currently used to help adults with type 2 diabetes manage their blood glucose levels and assist with weight loss. However, tirzepatide is not currently approved for adults with T1Dbecause if insulin doses are reduced too quickly, it could increase the risk of diabetic ketoacidosis (DKA), where acids build up in the blood.
Researchers like Dr Jennifer Snaith are running clinical trials of tirzepatide to find out if it is safe and beneficial for people living with T1D to take. Â
The TIRTLE 1 clinical trial
Early findings from the TIRTLE1 clinical trial suggest that tirzepatide can safely reduce the amount of insulin needed in people with T1D and obesity, helping them to keep their blood glucose within their target range and support weight loss. She now seeks to understand the biological mechanisms behind these results through the TIRTLE2 clinical trial.
The TIRTLE 2 clinical trial
In the TIRTLE2 clinical trial, 20 adults with T1D and excess weight will receive an injection of tirzepatide or placebo once a week alongside their usual insulin therapy for 4 weeks. The study will also include 10 people who are overweight but don’t have diabetes to compare their biological responses with the people who do have T1D.
Dr Snaith and her team will investigate how tirzepatide affects:
- insulin sensitivity
- glucagon response to low blood glucose
- hormonal responses to meals and overnight
- required insulin dose
- time in target blood glucose range
- blood vessel stiffness
- energy expenditure
Find out whether you might be eligible to take part in TIRTLE2 and how to sign up.
Treatments for T1D alongside insulin
In Australia, the only medication currently approved for T1D is insulin. This study will take a significant step towards developing personalised and effective treatments, with the potential to greatly improve health outcomes and quality of life for people living with T1D.
Treatments like tirzepatide can provide extensive benefits for people with type 2 diabetes, particularly protection against complications. TIRTLE2 will begin to address safety concerns associated with tirzepatide in T1D and shed light on how the therapy might provide benefits for people with T1D such as improving glucose regulation and reducing the need for insulin.
Insights from TIRTLE2 into how tirzepatide affects biological pathways could inform the development of more tailored treatments for T1D and refining existing therapies. Ultimately, this study is a crucial first step to pave the way for improved treatment options alongside insulin therapy to make living with T1D easier and safer.
About Dr Jennifer Snaith
Dr Jennifer Snaith is a researcher at the Garvan Institute of Medical Research where she conducts clinical trials in people with T1D. She is also an endocrinologist at St Vincent’s Hospital, where she sees patients and conducts research on insulin resistance, therapies to support blood glucose management, and cardiovascular risk.
Dr Snaith says she is motivated to improve the lives of people living with T1D through clinical service, advocacy and innovative research.
