Objective
The goals of this research are first, to find out if semaglutide improves kidney oxygenation and lowers albuminuria in people with type 1 diabetes, and second, to determine how semaglutide affects fluctuations in blood sugars and risk for low blood sugars. The overarching hypothesis of this proposal is that semaglutide improves kidney oxygen levels and lowers increased levels of protein in the urine in people with type 1 diabetes.
Background Rationale
Diabetic kidney disease is the leading cause of kidney failure in the developed world. Current diabetes treatments, such as control of high blood sugar, blood pressure and cholesterol have so far been unable to slow or prevent the development of diabetic kidney disease. Thus, identifying new and safe treatments for kidney disease in type 1 diabetes is a top priority. We are proposing a clinical trial to examine whether semaglutide, a new medication approved for use in type 2 diabetes, will improve kidney oxygen levels and lower urine protein levels in people with T1D. This will help determine whether semaglutide is a new, safe, and effective treatment for diabetic kidney disease in T1D.
Description of Project
Kidney disease is a common problem among people with type 1 diabetes and can lead to heart problems, kidney failure, and early death. The life expectancy of a child diagnosed with type 1 diabetes at age 10 is shortened by 17 years, a prognosis unchanged over the past four decades despite advances in blood sugar, cholesterol, and blood pressure control. Therefore, studies are needed to explore the impact of new therapies to improve kidney outcomes in type 1 diabetes. Therapies that have improved kidney and heart outcome in large trials of people with type 2 diabetes are promising options for this purpose.
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are a new class of diabetes medication shown to be effective in improving glucose control and reduce the risk of heart attack, stroke, and kidney disease in adults who have type 2 diabetes. However, the benefits of GLP-1RAs on kidney disease in type 1 diabetes are unknown. The current proposal will investigate whether semaglutide, a once weekly GLP-1RA injection, improves kidney oxygenation by magnetic resonance imaging and lowers increased levels of protein in the urine (an early marker of diabetic kidney disease).
At the start of the study, all 60 participants who take part will have a series of tests of their kidneys, including blood samples, urine samples, and kidney pictures by a magnetic resonance imaging (MRI) scan. After this, everyone in the study will be given a study drug to take daily for 6 months. For two-thirds of the people in the study this will be semaglutide, and for the other third it will be an injection that looks just like it but has no medicine in it (placebo). Which type of injection the person receives will be determined by chance. At the end of the study, we will repeat the series of kidney tests.
Anticipated Outcome
We anticipate that treatment with semaglutide will improve kidney oxygen levels and reduce the amount of protein in the urine in people with T1D. We also expect that treatment with semaglutide will lower fluctuations in blood sugars.
Relevance to T1D
Diabetic kidney disease is a common cause of heart disease, kidney failure and early death in type 1 diabetes. In fact, almost 40% of people with type 1 diabetes will develop diabetic kidney disease. Large studies in Europe and the United States have established that people with type 1 diabetes and diabetic kidney disease have almost 4-fold higher rates of death than the general population. The same studies have also shown that people with type 1 diabetes but without diabetic kidney disease have no higher rates of death than the general population. Despite advances in blood sugar monitoring, insulin therapy, and technology, some people with type 1 diabetes still develop diabetic kidney disease. It is therefore important to find new ways to protect against kidney disease. The purposes of this study are to find out if semaglutide, a new diabetes medication used in type 2 diabetes, can stop progression of kidney disease in people with type 1 diabetes.