Clinical trials are scientific studies that tell us if a new therapy or device works in humans and is safe. All new medical products must go through this process. Clinical trials are a necessary part of getting promising treatments from the lab and into clinics, so people can benefit—including those with type 1 diabetes (T1D).
The caveat: clinical trials don’t always work as expected for everyone. People with T1D might get the placebo instead of the actual treatment. Or, they might get the treatment, but it may not be effective for them. While this can be disappointing, it’s important to remember that clinical trials are an essential part of the process for arriving at new, effective therapies—and we can learn from them at every step of the way.
This Clinical Trials Awareness Day, we’re debunking some myths and misconceptions about clinical trials. What do researchers do when they don’t work? Why are placebos necessary? Why do they take so long?
Read on to find out.
When clinical trials “don’t work”
Assumption
A negative clinical trial—one that doesn't meet its primary endpoint or that yields inconclusive data—is a waste of time and money.
Reality
All data is good data, and we can learn lessons from clinical trials to design better studies that give us more information.
Clinical trials don’t always work the way researchers hope they will. For example, in T1D, a new therapy may not lower blood glucose, or it may increase the risk of severe hypoglycemic events. If the data from the trial isn’t positive, was it all a waste of time?
The answer is: absolutely not! The scientific method involves conducting an experiment or trial, analyzing the data, and using that data to figure out the next steps. Sometimes, researchers conclude that a drug might work better for a different indication. Other times, the trial design needs to be adjusted to make sure the right outcomes are being measured or the risk for serious side effects is reduced. Scientists and clinicians essentially use “negative” trial data to rule out what doesn’t work and craft a more informed plan going forward.
“The value of a clinical trial goes far beyond whether the drug ‘works.’ We can learn critical information from mechanistic studies that allow us to fine-tune our approaches, implement personalized and precision medicine, and ultimately improve outcomes for everyone living with T1D,” explained Joshua Vieth, Ph.D., Senior Director of Research at Breakthrough T1D. Here are some case studies that help explain this idea.
Diamyd® is a disease-modifying therapy that works by stopping the autoimmune destruction of insulin-producing beta cells. After demonstrating safety, Diamyd Medical initiated a phase 2 clinical trial for Diamyd® in Europe (DIAGNODE-2) in 2017. Initial readouts suggested that Diamyd® might be working—some people had lower blood sugar. However, at the end of the trial, there was not a clinically meaningful difference in C-peptide, a biomarker for insulin production.
The investigators didn’t give up. After taking a closer look at the data, they noticed that a portion of people achieved superior glycemic control compared to others. Going a step further, they found that the “responders” had a specific genetic marker (HLA DR3-DQ2). This marker is a risk factor for T1D that about 40% of the T1D population has.
Armed with this new knowledge, Diamyd Medical initiated a Breakthrough T1D-funded, global phase 3 trial for Diamyd® (DIAGNODE-3), targeted towards young adults and teens with the “responder” genetic marker and early stage T1D. The trial is currently progressing as planned.
Had the clinical researchers not done what they do best—ask questions and look for answers—Diamyd® would likely not have continued through the clinical pipeline.
Regulatory T cells help suppress immune responses. The Sanford Project T-Rex Trial, initiated in 2016, examined whether taking a person’s regulatory T cells, expanding them outside of the body, and putting them back in could help curb the autoimmune attack on beta cells. This was a phase 2 study in children eight to 17 years old with recent T1D onset.
In the end, the trial did not meet its primary endpoint as measured by C-peptide. Similar to the Diamyd® study, the researchers weren’t discouraged by this. They noticed that different people’s regulatory T cells grew at different rates outside of the body. Wondering why, they performed a genetic analysis of the cells and found something intriguing: regulatory T cells that grew more slowly correlated with better C-peptide when put back into the body.
Researchers concluded that it wasn’t the number of regulatory T cells that mattered, but rather the “quality.” This critical finding spurred follow-up investigations into designing new and innovative drugs that target these cells, pre-screening people to identify who might benefit from them, and incorporating mechanistic biological studies like this into clinical trial design.
SGLT (sodium-glucose cotransporter) is a protein that helps cells in the small intestine and kidney take up glucose from the blood. SGLT inhibitors that target kidney cells prevent them from absorbing glucose from the blood, so it gets excreted as waste. This class of drugs has shown benefits for glycemic control and reduced risk of complications in T2D, and researchers predicted that people with T1D could experience similar benefits.
In 2015, Lexicon Pharmaceuticals initiated three phase 3 clinical trials (inTandem1, inTandem2, and inTandem3) investigating the use of the SGLT inhibitor sotagliflozin (Zynquista™) in people with T1D and chronic kidney disease (CKD) as an adjunct therapy to insulin for blood glucose control. The results revealed clinically meaningful reductions in HbA1c—however, this was associated with a considerable risk for diabetic ketoacidosis (DKA). Lexicon tried their hand and submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) in 2024. In the end, the FDA rejected sotagliflozin for people with T1D and CKD, and Lexicon shut down their T1D program—a disappointing loss for the T1D community.
As these events were unfolding, researchers saw an opportunity: reduce the risk for DKA so people with T1D and CKD can experience the benefits of glucose control with sotagliflozin. In 2019, Breakthrough T1D helped publish international consensus guidelines for DKA risk mitigation for people with T1D treated with SGLT inhibitors. New SLGT inhibitor trials began to emerge with specific DKA risk reduction strategies, such as device-based ketone monitoring. This includes SUGARNSALT: a phase 3, Breakthrough T1D-funded trial that is currently enrolling (and one of many SLGT inhibitor trials that Breakthrough T1D is supporting).
These newer trials are paving the way for safe use of SGLT inhibitors in T1D to reduce kidney complications and improve blood glucose. Soon-to-be advancements in ketone monitoring, such as continuous ketone monitor (CKM) integration with continuous glucose monitors (CGMs) and consensus guidelines, will help people with T1D feel safe and confident using this class of drugs.
GLP-1 (glucagon-like peptide 1) is a naturally occurring hormone that the body releases in the gut after eating. It stimulates insulin production, blocks glucagon, reduces blood sugar, and induces the sensation of feeling full. GLP-1 receptor agonists mimic these effects and have shown incredible promise in T2D. One such example is liraglutide (Victoza®).
In 2013-2014, Novo Nordisk initiated two phase 3 clinical trials (ADJUNCT ONE and ADJUNCT TWO) for use of liraglutide as an adjunct therapy to insulin for people with T1D to lower blood sugar. Liraglutide improved HbA1c and bodyweight but also caused an increased rate of symptomatic hypoglycemia at higher doses. Based on these results, the company decided to terminate their pursuit of this therapy for T1D and did not submit an application to the FDA.
Knowing the potential benefits of GLP-1 receptor agonists for people with T1D, Breakthrough T1D continued to invest in this space to gather more clinical data and optimize trial design. This includes strategies for hypoglycemia risk reduction, especially since this class of drugs can increase insulin sensitivity.
Lo and behold, Eli Lilly recently initiated a recruiting phase 3 clinical trial (SURPASS-T1D-1) that will test whether tirzepatide (Mounjaro® or Zepbound®), a dual GLP-1/GIP receptor agonist, can improve blood glucose control in people with T1D who are obese or overweight, alongside insulin therapy. This is the first industry-sponsored clinical trial for tirzepatide in T1D.
While there are currently no GLP-1 receptor agonists approved for T1D, it’s hugely encouraging that companies are investing in this space. Between this and several Breakthrough T1D-funded trials, we are sure to see the future of GLP-1 receptor agonists for glucose control in T1D sooner rather than later.
The low-down on placebos
Assumption
It’s not fair for people with T1D to get a placebo instead of the study drug since it doesn’t do anything.
Reality
Placebos are required to know if a new therapy is working, and by participating in clinical trials you will receive top-tier care and contribute to medical breakthroughs that could help the entire T1D community.
Placebo
A placebo is a substance or procedure that does not contain any active ingredients and has no therapeutic effect. It usually looks similar and is given the same way as the therapy that it is being tested against.
Placebos are a necessary part of ethical, scientifically rigorous clinical trial design. Without them, researchers wouldn’t be able to tell if a new therapy has a clinically meaningful effect or not.
An important aspect of placebo-controlled trials is “blinding” participants, and usually clinicians, from knowing if they are giving or receiving the study drug or a placebo. This accounts for the placebo effect, which occurs when a person feels better, even though they received a placebo, because they believe that it’s having an effect. By separating the placebo effect from the actual biological effects of a new therapy, researchers can draw stronger conclusions about whether it will have a clinical benefit.
Clinical trials, especially at earlier stages, are also designed to test safety. A phase 1 trial is usually the first time that a new therapy is being put into humans. Without a placebo group, researchers wouldn’t have a clear picture of any side effects that a new treatment may have—which is critical for advancing to the next trial phases.
Clinical trials must be designed ethically: prioritizing safety, transparency, and clinical value. Placebos are a part of this, and they shouldn’t be a deterrent to enrolling in trials. People in the placebo group get state-of-the-art clinical care and are contributing to the body of knowledge that helps researchers and regulators make the right decisions about new therapies—which at the end of the day, benefits the entire T1D community.
The waiting game
Assumption
Clinical trials take too long and as such are not worth supporting.
Reality
Clinical trials take a long time because they thoroughly evaluate if a new therapy is safe and has a clinical effect before being available to everyone.
Clinical trials require coordination between lots of people: identifying study sites, making sure the clinics have the right personnel to administer a new treatment, making enough high-quality drug to conduct trials, and recruiting eligible participants. This also includes communication with regulatory agencies and extensive paperwork, data review and analysis by scientists and clinicians, writing up and publishing results, and ethics reviews.
It’s true: clinical trials take a long time. But, it’s all in the name of prioritizing people’s health, and most would agree that getting a new therapy that hasn’t been fully vetted wouldn’t be the best idea. Often, recruiting enough people is a major barrier to the advancement of trials. While many members of the T1D community participate in clinical trials, we need more people to accelerate the pace.
Conclusion: Clinical trials are thoughtfully designed—and essential to our health
Reality
Without clinical trials, we wouldn’t have access to the life-changing therapies that are available today.
Money, time, and energy spent on clinical trials is well worth the investment. Clinical trials, in essence, are the scientific process of making sure that a new therapy is safe and effective before it gets to people with T1D. Researchers learn from unexpected results to better decide on next steps, and each aspect of trial design is well thought out and has a specific purpose. While they often take many years, in the end it’s worth it.
In short: trust the process!
“Taking part in a clinical trial is such an important contribution to the T1D field. Beyond determining whether the treatment works, we are learning critical information about how the cells of the body respond. This opens the door for next generation approaches and allows us to take a giant step forward in the development of treatments and cures. Your participation in a trial provides long-term benefits to all those currently living with, or at risk of developing T1D.”
Joshua Vieth, Ph.D., Senior Director of Research at Breakthrough T1D
Participate in clinical trials
Contribute to scientific advancements and drive T1D breakthroughs by participating in clinical trials. With your help, we can move clinical trials along faster—and get the latest and greatest T1D therapies to people sooner!
