There is a deep unmet need for therapies in addition to insulin for glucose control in people with T1D. This is especially true for those with additional complications like CKD. Today, a U.S. Food and Drug Administration (FDA) advisory committee recommended against the agency approving Lexicon’s sotagliflozin for blood glucose control in individuals with T1D and CKD. Breakthrough T1D believes this drug has benefits for people with T1D and those benefits outweigh the risks.
The case for more therapies
For over 100 years, insulin therapy has been the main treatment for T1D. Better insulin options and new technologies, like continuous glucose monitors and automated insulin delivery systems, have improved health and quality of life for many people with T1D. There is nothing that people with T1D cannot accomplish. But, by nearly every health-related quality of life metric, people with T1D score lower than individuals without T1D. This includes general health, mental health, vitality, physical functioning, social functioning, and others.
If you look specifically at T1D metrics, a similar picture appears. Only 26% of individuals with T1D achieve an HbA1c level under 7%, the American Diabetes Association’s recommended HbA1c target to reduce the risk of long-term diabetes-related complications like cardiovascular and renal disease and diabetic retinopathy.
Despite the significant advances that Breakthrough T1D has been instrumental in realizing, people with T1D are not doing well enough. We need tools that make it easier to do better.
What is sotagliflozin?
Sotagliflozin is an SGLT (sodium-glucose co-transporter) inhibitor. SGLT inhibitors are oral medications originally developed for people with type 2 diabetes (T2D). They lower blood sugar by preventing the kidneys from reabsorbing glucose, leading to the excretion of sugar through the urine.
In addition to improving blood sugar, this class of drugs provides transformative benefits and have been approved for heart and kidney health in people with T2D and people without diabetes. In addition, they promote weight loss and blood pressure reduction.
Benefits of sotagliflozin for people with Chronic Kidney Disease
It has long been recognized that maintaining tight glucose control is crucial for preventing chronic kidney disease (CKD) in individuals with T1D. Recent data indicate that for those with T1D who already have CKD, there is a significant correlation between high HbA1c levels and an accelerated loss of kidney function. Therefore, effective glucose management is vital for individuals with both T1D and CKD to avert serious health complications.
In addition to improving glucose control, sotagliflozin has shown improvement in CKD outcomes in large trials of people with T2D. It is reasonable to expect these benefits would also be seen in those with T1D who also have CKD. While we do not yet have data on long-term kidney outcomes associated with sotagliflozin in T1D, we are encouraged by data demonstrating that sotagliflozin improves key biomarkers of kidney function in people with T1D.
The risk of diabetic ketoacidosis
There is one key consideration for the safe use of sotagliflozin: the risk of diabetic ketoacidosis (DKA).
Using SGLT inhibitors can increase the risk of DKA in people with T1D, so it’s important to monitor and manage this risk. In 2018, experts came together to address these concerns. Their findings led to an international agreement in 2019 on how to reduce the risk of DKA in people with T1D who are using SGLT inhibitors.
However, DKA is a risk for everyone with T1D, not just those taking SGLT inhibitors. It’s important to be aware of DKA as a regular part of managing T1D.
Breakthrough T1D has long supported research to advance safe, effective use of SGLT inhibitors in T1D
Breakthrough T1D’s Improving Lives program supports the development of SGLT inhibitors for T1D; this includes trials to assess benefits and risks of this drug class in T1D, as well as device-based and other strategies for DKA risk mitigation. SGLT inhibitors are FDA approved for T2D and certain non-diabetic populations such as those with CKD or heart failure, and they are used by some people with T1D off-label. Our work supports studies to build a body of evidence that will allow people with T1D to improve health outcomes through safe and effective use of SGLT inhibitors.
What comes next?
Breakthrough T1D believes the benefits outweigh the risks for people with CKD and T1D and sotagliflozin should be approved. That’s why Sanjoy Dutta, Ph.D., Breakthrough T1D Chief Scientific Officer, delivered public comments in support of the drug’s approval today.
As the formal review process moves forward, Breakthrough T1D will continue to invest in research to develop therapies for kidney disease in T1D that can help people live longer and healthier lives. While the advisory committee’s recommendation plays a critical role, it is not the only consideration in the final decision of approval (or not). The overwhelming majority of people with diabetes and world-renowned healthcare providers who commented were in agreement with Breakthrough T1D that the drug should receive approval.
The FDA are required to make a decision by December 20, 2024.
