Heart and kidney complications remain a major concern for people living with type 1 diabetes (T1D). While there are some therapies available to reduce the risk of these complications, the T1D community urgently needs more options. SGLT inhibitors (SGLTi), which have proven effective in people with type 2 diabetes (T2D) and people without diabetes, are a potential solution, but there have been several roadblocks in their development. To overcome these challenges and accelerate SGLTi for people with T1D, Breakthrough T1D spearheaded a publication laying out the path forward.
The Publication: A Roadmap for SGLTi
The publication, titled “SGLT Inhibitors for Heart and Kidney Disease in Type 1 Diabetes,” was published in Diabetes Care in September 2026. Jonathan Rosen, Ph.D., Senior Director of Research and lead of our Improving Lives program, led the charge with several Breakthrough T1D collaborators including experts in endocrinology, nephrology, and cardiology. The goal of this work is to give researchers a roadmap for advancing safe and effective use of SGLTi in the T1D population, including expected benefits and risks based on the data we have available, clinical trial design considerations, and diabetic ketoacidosis (DKA) risk mitigation strategies.
Key Takeaways
- People with T1D urgently need more heart and kidney therapies.
- SGLTi works in people with T2D and people without diabetes, and we expect people with T1D to experience similar heart and kidney benefits; however, these benefits have not been demonstrated yet.
- DKA is a real risk of SGLTi, but strategies to reduce this risk—including continuous ketone monitoring—have the potential to enable safer use of these therapies in the T1D population.
- Smart design of pivotal clinical trials for SGLTi will make them smaller, less expensive, and quicker without cutting corners on safety.
Heart and Kidney Complications: An Unsolved Problem in T1D
People living with T1D are at a heightened risk of developing both heart and kidney disease in their lifetimes. Chronic kidney disease (CKD) can progress to kidney failure, in which a transplant or dialysis is needed to survive. Kidney disease also amplifies the risk of heart disease, which includes heart failure, atherosclerotic cardiovascular disease, and more.
~30%
Estimated lifetime risk of developing CKD in people with T1D
18%
Prevalence of heart failure in people with T1D and CKD
1.5%
Prevalence of heart failure in people with T1D and no kidney disease
3-5x
Increased incidence rate of hospitalization and mortality from heart failure in people living with T1D compared to those without diabetes
While some therapies exist to help slow the progression of heart and kidney disease, there are simply not enough available—and no treatments exist to prevent them altogether.
What are SGLT Inhibitors?
SGLTi, or sodium-glucose cotransporter inhibitors, are a class of medications that block glucose transport in the kidneys. This allows for excretion of excess sugar through the urine, which ultimately lowers pressure inside the kidney’s filtration system. These drugs also ease strain on the heart.
SGLTi were originally developed for blood-sugar management in people with T1D, but they were not approved due to an increased risk for DKA (more on that later). Yet, SGLTi have shown tremendous benefits for heart and kidney protection in people with T2D and without diabetes, independent of their effects on lowering blood sugar. People with T1D were not included in these clinical trials, even though we expect similar benefits. That’s why Breakthrough T1D is taking the lead to advance SGLTi to treat heart and kidney disease in the T1D community.
What We Know about SGLTi from Clinical Trials
We have extensive data on the benefits of SGLTi in people with T2D and people without diabetes. In fact, these medications are the frontline therapy for treating heart failure and kidney disease. Based on an analysis of several clinical trials in these populations treated with SGLTi:
40%
Reduced risk of CKD onset or progression
~30%
Reduced risk of heart failure hospitalization or urgent visits
People with T1D have historically been excluded from larger SGLTi clinical trials studying heart and kidney benefits, which explains why we don’t have as much information on its effectiveness in T1D. Yet, we can extrapolate some of the expected benefits based on available data from smaller trials.
20-50%
Reduction in a marker of kidney damage (pooled data from several trials)
5-15%
Projected reductions in 5-year kidney failure risk and 10-year heart disease risk
Based on the proven heart and kidney benefits of SGLTi, researchers think that SGLTi will work in T1D, too. But we haven’t proven that yet. The bottom line is that we need more data around use of SGLTi in T1D—and thoughtfully designed clinical trials will help us achieve that sooner.
The Path to Approval: Surrogate Endpoints
For clinical trials looking at heart and kidney outcomes, traditional endpoints are often progression to kidney failure or death from heart or kidney complications. These endpoints are difficult to study, especially in T1D, because these trials require lots of participants and may take a very long time.
One solution: surrogate endpoints. These are biomarkers, or biological markers, that serve as a proxy for how an individual feels, functions, or survives and can be used in place of traditional endpoints in a clinical trial if they are recognized by regulatory agencies as clinically meaningful. One example is HbA1c, which can assess the risk of complications, or C-peptide, which is often used to assess whether disease-modifying therapies can preserve insulin-producing beta cells. There are also bridging biomarkers, which are endpoints that can be used to extrapolate the effectiveness of a treatment from one indication or population to another, like from T2D to T1D. Clinical trials in T1D that use these kinds of endpoints can often be smaller, less expensive, and quicker, while still providing critical information on safety.
Bridging Biomarker Example: Finerenone
Finerenone (brand name Kerendia) was recently approved for CKD in people with T1D. The endpoint of this clinical trial was urinary albumin-to-creatinine ratio (UACR), a measure of kidney damage that can be detected much sooner than traditional endpoints that clinical trials in CKD have relied upon. In studies testing finerenone in T2D, the improvements in UACR correlated with long-term kidney benefits. Based on this and the fact that finerenone was ultimately approved for people with T2D and CKD, the U.S. Food and Drug Administration (FDA) authorized use of UACR as a bridging biomarker to accelerate finerenone for T1D.
Because the benefits of SGLTi are already so well understood in other populations, large scale clinical trials with traditional endpoints may not be needed to establish their benefit in T1D, especially for kidney disease. In cases like this, bridging biomarkers can be a more strategic approach to clinical trial design that can accelerate SGLTi therapies for the T1D community.
Enabling Safe SGLTi Use with DKA Risk Mitigation
The major drawback of SGLTi use in T1D is that there is about a 3-fold increase in DKA risk. DKA is a life-threatening complication that occurs when the body doesn’t have enough insulin, leading to the breakdown of fat for energy instead of sugar and eventually ketone buildup in the blood. In people with T1D, SGLTi increases DKA risk partly because it reduces blood-sugar levels, which may lower insulin doses.
Ongoing SGLTi trials in T1D have protocols in place to monitor ketones and empower participants to act when levels start rising. Recently, the first continuous ketone monitor (CKM) for T1D was approved, and CKM has tremendous promise to be another tool that can help people with T1D safely achieve the benefits of SGLTi. Breakthrough T1D is funding several studies to uncover how CKM can most effectively reduce DKA risk, so we’ll continue amassing important safety data as SGLTi move through the clinical pipeline.
SGLTi Clinical Trials in T1D
| Clinical Trial | Identifier | Drug(s) | Population | Primary Endpoint |
|---|---|---|---|---|
| SUGARNSALT | NCT06217302 | Sotagliflozin | T1D and CKD | eGFR |
| SOPHIST | NCT06435156 | Sotagliflozin | T1D and heart failure | Heart failure symptoms |
| Steno 1 | NCT06082063 | Sotagliflozin, semaglutide, finerenone | T1D and high risk of heart disease | Incidence of cardiovascular events |
| PLUTO | NCT06147232 | Sotagliflozin | T1D and CKD | Kidney oxygenation |
The Future of SGLTi in T1D
Technically speaking, there have been no SGLTi approved specifically for use in T1D in the U.S. Yet, multiple SGLTi are approved for adults with heart failure or CKD with or without diabetes, and this does not exclude people with T1D—but clinical use remains low. More trials and more data are needed to aid in the clinical adoption of SGLTi in T1D, and decisions around SGLTi use ultimately lie with individuals and their care teams.
The phase 3 SUGARNSALT trial (which includes DKA risk mitigation) will provide critical evidence around the SGLTi sotagliflozin in people with T1D and CKD and, if favorable, could lead to consideration for regulatory approval. Going forward, thoughtfully designed clinical trials will help get the data needed for future regulatory decisions and clinical adoption of SGLTi. Along with current strategies to prevent DKA, continuous advancements in CKM promise to improve the benefit-to-risk ratio of SGLTi for people with T1D.
In collaboration with researchers, clinicians, regulators, and companies around the world, Breakthrough T1D will keep advancing safe, effective use of SGLTi so that people with T1D will have another tool for healthier hearts and kidneys—and longer, healthier lives.
