Objective
This study’s goal is to understand the long-term benefits and risks of GLP-1RAs, SGLT2i, and statins in people with T1D. Large randomized clinical trials are the gold standard to accomplish this goal, but such trials in T1D would be extremely costly and are unlikely to happen soon. To address this gap, our study will use an alternative approach called “target trial emulation.” This powerful method applies advanced statistical techniques to real-world data to closely mimic what a randomized trial would show. We will analyze electronic health records from the Optum Labs Data Warehouse, which includes data from over 300 million people in the United States. From this dataset, we have identified approximately 460,000 children and adults with T1D from more than 60 health systems, making this one of the largest and most diverse T1D populations ever studied.
Objective 1: Benefits and risks of newer versus older GLP-1RAs in T1D
We will compare newer GLP-1RAs (tirzepatide, semaglutide) with older GLP-1RAs (albiglutide, dulaglutide, exenatide, liraglutide, lixisenatide) to see how they affect long-term health in people with T1D. We will examine whether newer medications are linked to lower risks of cardiovascular events (heart attack, stroke), heart failure, and kidney failure. We will also assess side effects, including stomach-related symptoms, diabetic ketoacidosis (DKA), and severe low blood sugar, to understand whether newer drugs are as safe as older ones. Finally, we will compare results in people with T1D to those seen in people with type 2 diabetes to determine whether these treatments work similarly across diabetes types.
Objective 2: Benefits and risks of SGLT2i in T1D
We will evaluate whether people with T1D who use SGLT2i have lower risks of cardiovascular events (heart attack, stroke), heart failure, kidney failure, and vision-threatening eye disease compared with those who do not use these medications. At the same time, we will carefully examine potential side effects, including DKA and genitourinary infection, to better understand the overall safety of these drugs in T1D. We will compare findings in T1D with those in type 2 diabetes to assess whether benefits and risks are similar across diabetes types.
Objective 3: Benefits and risks of statins in children (6-17 years) and young adults (18-39 years) with T1D
We will study whether statins reduce the risk of cardiovascular events (heart attack, stroke) in children and young adults with T1D. Because these drugs are often started at a young age, we will also examine whether statin use affects growth in children or leads to side effects such as muscle or liver problems. Results will be compared between people with type 1 and type 2 diabetes to determine whether these treatments work similarly across diabetes types.
Background Rationale
People with type 1 diabetes (T1D) face a high risk of developing cardiovascular and kidney disease. However, there is limited evidence to guide the best ways to prevent cardiovascular and kidney complications in this high-risk population.
In people with type 2 diabetes, newer medications—glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2i)—have revolutionized care. These drugs reduce the risk of cardiovascular disease, kidney failure, and death, in addition to improving blood sugar control and promoting weight loss. Newer GLP-1RAs, such as tirzepatide and semaglutide, appear especially powerful. There is strong interest in using these medications in people with T1D, but their long-term risks and benefits in T1D are unknown. Most large cardiovascular and kidney outcome trials of GLP-1RAs and SGLT2i have excluded people with T1D. Smaller trials in T1D have mainly focused on short-term outcomes like blood sugar or weight, rather than serious clinical events such as heart attacks or kidney failure. Some studies have also raised safety concerns with these medications, including higher risks of diabetic ketoacidosis and low blood sugar. Because of these uncertainties, GLP-1RAs and SGLT2i are not currently approved for T1D by the United States Food and Drug Administration.
The 2026 American Diabetes Association Guidelines include a new recommendation stating that GLP-1RAs can be used for weight management in people with T1D and obesity. While this represents an important change, the narrow focus on weight loss is a limitation, given the potential cardiorenal benefits of GLP-1RAs. We need evidence on how GLP-1RAs and SGLT2i affect long-term cardiovascular and kidney outcomes in people with T1D before new recommendations can be made.
Similar evidence gaps exist for older therapies. The guidelines recommend starting statins in people with T1D who are at high cardiovascular risk as early as age 6 years. However, these recommendations are based largely on expert opinion rather than direct trial evidence in T1D, especially in children and young adults.
Large randomized clinical trials are the gold standard for answering these critical questions, but such trials in T1D would be extremely costly and are unlikely to happen soon. To address this gap, our study will use an alternative approach called “target trial emulation” analyzing “big data” collected during routine care. This powerful method applies advanced statistical techniques to real-world data to closely mimic what a randomized trial would show.
Description of Project
People with type 1 diabetes (T1D) face a very high risk of developing cardiovascular and kidney disease. However, there is limited evidence to guide the best ways to prevent cardiovascular and kidney complications in this high-risk population.
In people with type 2 diabetes, newer medications—glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2i)—have revolutionized diabetes care. These drugs reduce the risk of cardiovascular disease, kidney failure, and death, in addition to improving blood sugar control and promoting weight loss. Newer GLP-1RAs, such as tirzepatide and semaglutide, appear especially powerful. There is strong interest in using these medications in people with T1D, but their long-term risks and benefits in T1D are unknown. Most large cardiovascular and kidney outcome trials of GLP-1RAs and SGLT2i have excluded people with T1D. Smaller trials in T1D have mainly focused on short-term outcomes like blood sugar or weight, rather than clinical events such as heart attacks or kidney failure. Some studies have also raised safety concerns with these medications, including higher risks of diabetic ketoacidosis and low blood sugar. Because of these uncertainties, GLP-1RAs and SGLT2i are not currently approved for T1D by the United States Food and Drug Administration.
The 2026 American Diabetes Association Guidelines include a new recommendation stating that GLP-1RAs can be used for weight management in people with T1D and obesity. While this represents an important change, the narrow focus on weight loss is a limitation, given the potential cardiorenal benefits of GLP-1RAs. We need evidence on how GLP-1RAs and SGLT2i affect long-term cardiovascular and kidney outcomes in people with T1D before new recommendations can be made.
Similar evidence gaps exist for older therapies. The guidelines recommend starting statins in people with T1D who are at high cardiovascular risk as early as age 6 years. However, these recommendations are based on expert opinion rather than direct trial evidence in T1D, especially in children and young adults.
Large randomized clinical trials are the gold standard for answering these critical questions, but such trials in T1D would be extremely costly and are unlikely to happen soon. To address this gap, our study will use an alternative approach called “target trial emulation.” This powerful method applies advanced statistical techniques to real-world data to closely mimic what a randomized trial would show. We will analyze electronic health records from the Optum Labs Data Warehouse, which includes data from over 300 million people in the United States. From this dataset, we have identified approximately 460,000 children and adults with T1D from more than 60 health systems, making this one of the largest and most diverse T1D populations ever studied.
Our goal is to evaluate the long-term benefits and risks of GLP-1RAs, SGLT2i, and statins in people with T1D. By linking these treatments to clinical outcomes, such as heart disease, kidney failure, and safety events, this study will provide critical evidence to improve clinical guidelines, inform regulatory decisions, and ultimately reduce the burden of cardiovascular and kidney disease in people living with T1D.
Anticipated Outcome
Helping bring new treatments to people with type 1 diabetes (T1D)
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) are not currently approved for people with T1D because of limited efficacy and safety data. Our study will help fill this gap by using real-world data from ~460,000 children and adults with T1D to examine how these medications affect heart and kidney health, as well as their safety. This will be one of the largest study in T1D and will provide important information about the benefits and risks of these treatments. Together with results from smaller clinical trials of T1D, these findings can support efforts to make effective heart- and kidney-protective medications more widely available to people with T1D.
Expanding clinical recommendations on GLP-1RA and SGLT2i use in T1D
In 2026, the American Diabetes Association updated its guidelines to recommend GLP-1RAs for weight management in people with T1D and obesity, based in part on real-world evidence. While this was an important step forward, the recommendation focuses only on weight loss and does not address potential benefits for heart and kidney health. Our study will generate new real-world evidence on whether GLP-1RAs and SGLT2i can also help prevent heart and kidney diseases in people with T1D. This information could lead to broader treatment recommendations that better reflect the full range of benefits these medications may offer.
Improving guidance on early statin use in young people with T1D
Statins are recommended for young people with T1D who are at high risk for heart disease, but these recommendations are largely based on expert opinion rather than direct evidence in T1D. As a result, statins are used much less often than recommended in children and young adults with T1D. Our study will include more than 200,000 people with T1D under the age of 40 and will provide much-needed information on the long-term benefits and safety of statins in this group. These findings can help improve clinical guidelines and support earlier, more effective prevention of heart disease in young people living with T1D.
Relevance to T1D
People with type 1 diabetes (T1D) are at very high risk for cardiovascular and kidney disease, yet there is limited evidence to guide how best to prevent these serious complications. Effective new medications for protecting the heart and kidneys in people with type 2 diabetes—such as Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2i)—have not been adequately studied in people with T1D. As a result, people with T1D and their clinicians often lack clear information about whether these treatments are safe or beneficial. Evidence gaps also extend to established therapies. The guidelines recommend statin initiation in high-risk people with T1D beginning as early as age 6 years; however, these recommendations are based on expert opinion and extrapolation from non-T1D populations. The optimal timing and long-term effectiveness and safety of statin therapy in children and young adults with T1D remain uncertain, underscoring the need for additional research.
This study directly addresses this critical gap. By using real-world data from one of the largest and most diverse groups of people with T1D ever assembled, we will evaluate whether these medications reduce the risk of heart disease, kidney failure, and other serious outcomes in people with T1D, and whether they can be used safely. By providing long-term evidence on cardiorenal therapies in T1D, this research has the potential to improve clinical guidelines, support regulatory decisions, and expand access to effective treatments in T1D. Ultimately, this work aims to reduce the burden of cardiovascular and kidney disease and improve long-term health outcomes for people living with T1D.