Objective
The purpose of the project
The primary objective of the project is to estimate the effect of three months of sotagliflozin treatment on renal oxygenation in individuals with type 1 diabetes and chronic kidney disease. Secondary measures are to estimate the effect on kidney function by measuring the excretion of albumin (protein) in the urine and examining the effect on other markers of kidney disease.
Background Rationale
Sodium glucose cotransporter inhibitors (SGLTi) affect the transport of sugar in the kidneys by inhibiting the reabsorption and thereby increasing the excretion of sugar in the urine. This causes decreasing blood sugar without increased risk of low blood sugar as well as weight loss. The treatment was approved for people with type 2 diabetes in 2012. Later, several studies have shown that SGLT2 inhibitors have beneficial effects on the cardiovascular system and on the kidneys in people with type 2 diabetes. The SGLT2 inhibitors are therefore recommended for people with type 2 diabetes and pre-existing cardiovascular disease, especially heart failure, or chronic kidney disease.
The beneficial effects on the heart and kidneys seen in type 2 diabetes may also be seen in the treatment of type 1 diabetes, which, like type 2 diabetes, carries an increased risk of cardiovascular disease. Unfortunately, there is currently no prospect that such studies will be made.
Description of Project
Sodium glucose cotransporter 1 and 2 (SGLT) inhibitors affect the transport of sugar in the kidneys by inhibiting the reabsorption and thereby increasing the excretion of sugar in the urine. This causes decreasing blood sugar without increased risk of low blood sugar as well as weight loss. The treatment was approved for people with type 2 diabetes in 2012. Later, several studies have shown that SGLT inhibitors have beneficial effects on the cardiovascular system and on the kidneys in people with type 2 diabetes. The SGLT inhibitors are therefore recommended for people with type 2 diabetes and pre-existing cardiovascular disease, especially heart failure, or chronic kidney disease.
The beneficial effects on the heart and kidneys seen in type 2 diabetes may also be seen in the treatment of type 1 diabetes, which, like type 2 diabetes, carries an increased risk of cardiovascular disease. Unfortunately, there is currently no prospect that such studies will be made.
The purpose of the project
The primary objective of the project is to estimate the effect of three months of sotagliflozin treatment on renal oxygenation in individuals with type 1 diabetes and chronic kidney disease. Secondary measures are to estimate the effect on kidney function by measuring the excretion of albumin (protein) in the urine and examining the effect on other markers of kidney disease.
Who can participate?
We will include 69 people with type 1 diabetes and increased protein excretion in the urine. You have to be minimum 18 years of age.
The trial is a cross-over trial with a total of seven visits
Endpoints:
Estimate of renal oxygenation and kidney function in individuals with type 1 diabetes and chronic kidney disease after treatment with sotagliflozin.
Anticipated Outcome
Estimate of renal oxygenation and kidney function in individuals with type 1 diabetes and chronic kidney disease after treatment with sotagliflozin. We will also look into potential benefits on heart function and if there are ethnic differences in how the kidney works and responds to treatment.
Relevance to T1D
Several studies have shown that SGLTi have beneficial effects on the cardiovascular system and on the kidneys in people with type 2 diabetes. The SGLTi are therefore recommended for people with type 2 diabetes and pre-existing cardiovascular disease, especially heart failure, or chronic kidney disease.
The beneficial effects on the heart and kidneys seen in type 2 diabetes may also be seen in the treatment of type 1 diabetes, which, like type 2 diabetes, carries an increased risk of cardiovascular disease. Unfortunately, there is currently no prospect that such studies will be made. The SGLTi were approved for type 1 diabetes i Europe and Japan in 2019, but the increased risk of diabetic ketoacidosis of 1-4% has been a limiting factor for more widespread use of this treatment. Because of this increased risk of ketoacidosis the treatment was withdrawn again from Europe in 2021. With this study we will gain important knowledge of the mechanisms related to the beneficial effects of SGLTi on kidney function and the effects on markers of nephropathy in type 1 diabetes. If as expected the beneficial effects on the cardiovascular system and kidneys are similar to those seen in type 2 diabetes these benefits may outweigh the risk of DKA in type 1 diabetes and the SGLTi will become available for the type 1 diabetes population protecting both the kidneys and the cardiovascular system. We will also try to explain the observed ethnic differences in prognosis and see if treatment can improve this.