From the Guidelines
SGLT2 inhibitors are not recommended for routine use in patients with Type 1 diabetes and end-stage renal disease (ESRD) due to their limited efficacy in this population and increased risk of adverse effects, particularly diabetic ketoacidosis (DKA) 1.
Key Considerations
- The primary mechanism of SGLT2 inhibitors, increasing urinary glucose excretion, is severely compromised in ESRD, rendering them ineffective for glycemic control.
- The safety profile of SGLT2 inhibitors in dialysis patients is not well established, and their use may increase the risk of ketoacidosis, particularly in patients with type 1 diabetes.
- Insulin therapy remains the cornerstone of treatment for type 1 diabetes patients with ESRD, with careful attention to dose adjustments based on dialysis schedule if applicable.
Alternative Treatment Options
- Other medication classes with better established safety profiles in this specific population should be considered for additional cardiovascular or renal protection.
- Close specialist supervision and frequent monitoring for ketosis and other adverse effects are necessary if SGLT2 inhibitors are used experimentally in this population.
Recent Evidence
- A recent study published in 2024 found that sotagliflozin, a dual SGLT1 and SGLT2 inhibitor, reduced the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure in people with heart failure or type 2 diabetes, CKD, and other cardiovascular risk factors 1.
- However, this study did not include patients with type 1 diabetes and ESRD, and the use of SGLT2 inhibitors in this population remains off-label and carries significant risks.
From the Research
Usage of SGLT2 Inhibitors in Diabetes Type 1 and ESRD
- The use of SGLT2 inhibitors in type 1 diabetes has been investigated as an add-on therapy to insulin, with studies showing significant reductions in glycated haemoglobin (HbA1c) concentration, fasting plasma glucose, body weight, and systolic blood pressure 2.
- SGLT2 inhibitors have been found to decrease bolus and basal insulin requirements, and reduce glucose excursions, with no significant increase in hypoglycemia rates 2.
- However, the use of SGLT2 inhibitors in type 1 diabetes has also been associated with an increased risk of diabetic ketoacidosis and genital tract infections 2.
- In terms of end-stage renal disease (ESRD), there is limited evidence on the use of SGLT2 inhibitors in this population, and more research is needed to determine their safety and efficacy in patients with ESRD.
- SGLT2 inhibitors have been shown to be effective in improving glycemic control and reducing body weight and blood pressure in patients with type 2 diabetes, and may be a useful treatment option for patients with type 2 diabetes and ESRD 3, 4.
Mechanism of Action
- SGLT2 inhibitors work by decreasing renal glucose reabsorption, thereby increasing urinary glucose excretion and lowering plasma glucose levels in patients with hyperglycemia 3, 4.
- This mechanism of action is insulin-independent, making SGLT2 inhibitors a useful treatment option for patients with type 1 and type 2 diabetes 3, 4.
Exercise and SGLT2 Inhibitors
- Regular exercise is important for patients with type 1 diabetes, and can help improve health and wellbeing, and achieve target lipid profile, body composition, and fitness and glycaemic goals 5, 6.
- However, exercise can also pose challenges for patients with type 1 diabetes, including fear of hypoglycemia, loss of glycaemic control, and inadequate knowledge around exercise management 5, 6.
- SGLT2 inhibitors may be a useful treatment option for patients with type 1 diabetes who exercise regularly, as they can help reduce glucose excursions and improve glycemic control 2.