From the Guidelines
SGLT2 inhibitors are not recommended for patients with Type 1 diabetes who have HFrEF (heart failure with reduced ejection fraction) due to the increased risk of diabetic ketoacidosis (DKA). The most recent and highest quality study, 1, highlights the risk of DKA associated with SGLT2 inhibitors, particularly in patients with Type 1 diabetes. Although SGLT2 inhibitors like dapagliflozin and empagliflozin have shown significant benefits in HFrEF patients, including reduced hospitalizations and mortality, the risk of DKA in Type 1 diabetes patients outweighs these benefits.
The mechanism of SGLT2 inhibitors increasing the susceptibility to DKA is multifactorial, including increased production due to reduction in insulin doses, increases in glucagon levels leading to increased lipolysis and ketone production, and decreased renal clearance of ketones 1. The study also notes that the use of SGLT inhibitors in people with type 1 diabetes requires careful assessment of underlying susceptibility, education regarding the risks, symptoms, and prevention strategies, and prescription of home monitoring supplies for b-hydroxybutyrate to minimize the risk of ketoacidosis.
For patients with Type 1 diabetes and HFrEF, alternative heart failure therapies should be optimized instead, including:
- ACE inhibitors or ARBs
- Beta-blockers
- Mineralocorticoid receptor antagonists
- Potentially sacubitril/valsartan
If heart failure management remains suboptimal, consultation with both cardiology and endocrinology specialists would be appropriate to discuss individualized risk-benefit assessment and potential close monitoring strategies if an SGLT2 inhibitor is still considered 1. The 2021 update to the 2021 ACC expert consensus decision pathway for optimization of heart failure treatment also notes that SGLT2 inhibitors are not approved for use in patients with type 1 diabetes due to increased risk of diabetic ketoacidosis 1.
In the context of real-life clinical medicine, prioritizing the safety of patients with Type 1 diabetes and HFrEF is crucial, and the potential benefits of SGLT2 inhibitors do not outweigh the risks of DKA. Therefore, alternative therapies should be prioritized, and SGLT2 inhibitors should only be considered in exceptional cases with close monitoring and consultation with specialists.
From the Research
Starting SGLT2 Inhibitor for HFrEF in Patients with Type 1 Diabetes
- The use of SGLT2 inhibitors in patients with Type 1 diabetes is not approved, but evidence suggests they can be beneficial in improving glycemic control and reducing insulin requirements 2, 3.
- A study on empagliflozin, an SGLT2 inhibitor, showed a clear beneficial effect on HbA1c, body weight, glucose variability, and total daily insulin use in patients with Type 1 diabetes, with no increase in hypoglycemia risk 2.
- However, the use of SGLT2 inhibitors in patients with Type 1 diabetes may come with a risk of diabetic ketoacidosis (DKA), although this risk can be mitigated with patient education and careful monitoring 2, 3.
- In patients with heart failure with reduced ejection fraction (HFrEF), SGLT2 inhibitors have been shown to have a beneficial effect on outcomes, including a reduction in all-cause mortality and heart failure hospitalization 4, 5.
- The pathophysiological mechanisms by which SGLT2 inhibitors may benefit heart failure likely differ depending on ejection fraction, but each represents interference with distinct pathways by which hyperinsulinemia may adversely affect cardiac structure and function 5.
- Patients with HFrEF and diabetes have a higher risk of mortality than those without diabetes, despite controlling for medical therapies and comorbidities 6.
Considerations for Starting SGLT2 Inhibitor
- Clinicians should weigh the potential benefits of SGLT2 inhibitors in patients with Type 1 diabetes and HFrEF against the potential risks, including DKA and genital infections 2, 3.
- Careful patient selection, education, and monitoring are necessary to minimize the risks associated with SGLT2 inhibitor use in patients with Type 1 diabetes and HFrEF 2, 3.
- The use of SGLT2 inhibitors in patients with Type 1 diabetes and HFrEF may require adjustments to insulin doses and close monitoring of glucose levels and kidney function 2, 3.