Episode Details

Episode 138: SGLT-2 Inhibitors in heart failure

Future doctor Enuka explains the use of sodium-glucose-linked cotransporter-2 inhibitors (SGLT-2 inhibitors) in heart failure. Dr. Arreaza adds his experience with these medications and emphasizes their role as an effective treatment for type 2 diabetes.  

Written by  Princess Enuka, MSIV, Ross University School of Medicine. Editing by Hector Arreaza, MD.

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Intro:

Heart failure is a major medical condition that affects millions of people worldwide. It is one of the leading causes of hospitalization and death in developed countries. Recently, SGLT2 inhibitors have emerged as a promising treatment option for heart failure. Today, we will discuss their benefits, their effectiveness, and their adverse effects.

SGLT2 inhibitors, also known as sodium-glucose-linked cotransporter-2 inhibitors, are a relatively novel class of drugs that have shown promise in heart failure treatment. This transporter reabsorbs glucose from the glomerular filtrate back into the bloodstream. Under normal circumstances, SGLT-2 reabsorbs 100% of the filtered glucose unless it is saturated (as in hyperglycemia) or blocked by medications. SGLT2 inhibitors increase the amount of glucose excreted in the urine, which leads to blood glucose reduction. Examples include empagliflozin, dapagliflozin, and canagliflozin.

SGLT-2 inhibitors have become a first-line therapy for diabetes mellitus. I heard before that it was used in Europe for T1DM, but it seems like they are no longer used, according to my most recent review of articles. SGLT2 inhibitors are not approved by the FDA for use in type 1 diabetes due to the risk of DKA. Princess, besides the benefits in diabetes, what else did you find in your review?

Benefits/Efficacy:

SGLT2 inhibitors have additional benefits beyond their glucose-lowering effects. One of the benefits of SGLT2 inhibitors is their ability to increase myocardial energy production, alleviate systemic microvascular dysfunction, and improve systemic endothelial function. 

Natriuresis and glucosuria mediated by SGLT2 inhibitors have been shown to lower cardiac pre-load and reduce pulmonary congestion and systemic edema, which is beneficial for heart failure management.
Studies have shown that these drugs can also improve cardiovascular outcomes in patients with heart failure with a reduced ejection fraction. 

Some studies:

The EMPEROR-Reduced trial demonstrated that empagliflozin, brand name Jardiance®, reduced the risk of cardiovascular death and hospitalization for heart failure in patients with reduced ejection fraction by 25% compared to placebo. Several clinical trials have also shown that this result is significant whether patients have type 2 diabetes or not. 

Also, in a multicenter, double-blind, randomized, placebo-controlled trial in patients with heart failure, treatment with dapagliflozin, brand name Farxiga®, improved heart failure-related symptoms and physical limitations after only 12 weeks of treatment. Patients treated with dapagliflozin had a significant, clinically meaningful improvement in the 6-minute walking test distance. The magnitude of these benefits was statistically and clinically significant, spanning all subgroups categorized. This included patients with and without type 2 diabetes and those with an ejection fraction above or below 60%.

Anecdote:

During a previous clinical rotation, I had a patient taking Jar