From insulin to immunotherapy: A century of discovery

The discovery of insulin 100 years ago transformed type 1 diabetes from a death sentence to a treatable condition. It ignited a century of discovery that has seen insulin and the way it’s delivered into the body dramatically improve, yet today, insulin remains the only treatment available for type 1 diabetes.

Insulin therapy can be frustrating and exhausting. People with type 1 diabetes need to work out the exact right amount of insulin to take multiple times every day, depending on what they eat, what they’re doing and how they’re feeling. Perfectly tiptoeing along this fine line day in, day out is near-impossible. As a result, only around 30% of people with type 1 diabetes get the sort of ideal blood glucose control that will reduce their risk of long-term diabetes complications(1). What’s clear is that we need a better alternative.

Immunotherapy flips the current approach to treating type 1 diabetes. Instead of replacing lost insulin, it works to protect what’s there by retraining the immune system to stop its attack on insulin-producing beta cells. Immunotherapies could help at three different stages of type 1 diabetes:

• Preventing or delaying an immune attack when given to people before a clinical diagnosis of type 1.
• Halting the immune attack in people newly diagnosed.
• Forming part of a cure for people already living with the condition. Research to replace or regenerate beta cells that have been destroyed is picking up pace. Once we can do this, immunotherapies could be used alongside beta cell therapy to protect these new cells in people who’ve lived with type 1 diabetes for many years.

Stopping type 1 in its tracks

At the time of clinical diagnosis, people with type 1 diabetes have up to 20% of their beta cells remaining. These surviving cells and the insulin they produce help to steady the ship, making blood glucose easier to manage. Even if we can’t preserve beta cells forever, evidence shows that preserving as many as possible for as long as possible can benefit blood glucose control for many years beyond the original treatment and is linked with long-lasting protection against future diabetes complications(2).

Several immunotherapies have now been shown to slow the progressive decline in beta-cell function in people newly diagnosed with type 1 diabetes(3), but more late-phase clinical trials are needed. The UK Type 1 Diabetes Immunotherapy Consortium, established by Diabetes UK and JDRF in 2014, is working to accelerate progress in this area so that treatments reach people with type 1 diabetes sooner.

This network of experts and research sites includes centres of excellence across the UK, where specialist teams are running immunotherapy trials, boosting recruitment to them, and attracting greater investment. Alongside this, scientists study and compare results from different trials to learn more about how the treatments work and who they work best for.

Turning a corner in type 1 prevention

Elsewhere, an enormous milestone was reached when, in 2019, TrialNet researchers revealed that it was possible to delay the onset of type 1 diabetes with immunotherapy.

The latest update from this trial shows the median time to a diagnosis of type 1 was two years in those receiving a placebo, but five years in those given the immunotherapy drug, teplizumab(4). That’s an average of three extra years free of type 1 diabetes and free of insulin therapy, the anxieties related to managing the condition or the worry of future complications.

Following these landmark findings, the Food and Drug Administration (FDA) in the U.S. is now considering whether to approve teplizumab for use in people at risk, with a decision expected as soon as July 2021. Not only would this be a major paradigm shift in the treatment of type 1 diabetes, but the approval of the first immunotherapy drug for type 1 diabetes will hopefully open the floodgates to more investment, more treatments, and – most importantly – more people with or at risk of type 1 diabetes benefitting from immunotherapies at different stages of the condition. We need to capitalise on this and help to smooth the path for approval in the UK and for other therapies to follow in the wake of teplizumab.

If teplizumab or other therapies that delay the onset of type 1 become available, it will also spark vital, a renewed focus on the next big question – how do you identify who to give the treatment to?

More than 85% of individuals with type 1 diabetes do not have a family history of the condition, so spotting everyone at risk will require a general population screening to detect genetic risk or autoantibodies. To get there, there will be important questions to answer on the feasibility of screening programmes, their cost-effectiveness and the psychological implications for individuals identified as being at high risk.

One hundred years after the discovery of insulin, we stand on the brink of the next treatment breakthrough for type 1 diabetes. But realising this potential requires research and healthcare communities, alongside people with diabetes, to pull together.

Curing or preventing type 1 diabetes is at the heart of our mission at Diabetes UK and despite the challenges ahead, the scene is now set for immunotherapy to transform the lives of people with or at risk of the condition.

References
1) NHS Digital, 2019. National Diabetes Audit Report 1: Care Processes and Treatment Targets 2018-19.
2) Steffes, M.W., Sibley, S., Jackson, M., Thomas, W. 2003. Beta-cell function and the development of diabetes-related complications in the diabetes control and complications trial. Diabetes Care, 26, 832–836.
3) Jacobsen, L.M., Bundy, B.N., Greco, M.N., Schatz, D.A., Atkinson, M.A., Brusko, T.M., Mathews, C.E., Herold, K.C., Gitelman, S.E., Krischer, J.P. and Haller, M.J., 2020. Comparing beta cell preservation across clinical trials in recent-onset type 1 diabetes. Diabetes Technology & Therapeutics, 22, 948-953.
4) Sims, E.K., Bundy, B.N., Stier, K., Serti, E., Lim, N., Long, A., Geyer, S.M., Moran, A., Greenbaum, C.J., Evans-Molina, C. and Herold, K.C. 2021. Teplizumab improves and stabilizes beta-cell function in antibody-positive high-risk individuals. Science Translational Medicine, 13, 583.