Beneficial impacts of SGLT-2 Inhibitors on Cardiovascular Disease

After several clinical trials associated with SGLT-2 inhibitors, this anti-diabetic drug class of medications is now linked to providing beneficial impacts on cardiovascular disease.

Sodium-glucose cotransporter-2 inhibitors, also known as SGLT2 inhibitors, are antidiabetic drug classes that exert their function by causing the kidneys to remove excess glucose through the urine. When utilized for the treatment of diabetes, SGLT2 inhibitors cause a reduction of blood glucose levels, hemoglobin A1C, and body weight (Zimmermann, 2016).

Recently, clinical trials such as DECLARE-TIMI (2019) and CREDENCE (2019) have shown that SGLT2 inhibitors have beneficial cardiovascular outcomes. 

Drugs that belong to the SGLT2 drug class are:  

*SGLT2s FDA approved for Heart failure with reduced ejection fraction with/without diabetes.

Beneficial outcomes of SGLT-2 inhibitors on Cardiovascular Disease

Such outcomes include a reduced incidence of cardiovascular death and heart failure hospitalizations in people with and without diabetes. Although the mechanism of action of how the cardioprotective effects are achieved is not fully understood, various hypotheses have surged. 

 These benefits include: 

  • Diuresis/natriuresis
  • Blood pressure reduction
  • Improved cardiac energy metabolism 
  • Inflammation reduction 
  • Adverse cardiac remodeling prevention
  • Ischemia
  • Decrease of oxidative stress
  • Improving vascular function

SGLT2 inhibitors are currently indicated in Europe and the USA as first or second-line treatments of type 2 diabetes mellitus (T2DM) in patients with established cardiovascular disease, high/extremely high cardiovascular risk, renal disease, or heart failure. Additionally, the use of dapagliflozin and empagliflozin have recently been approved to be utilized in patients with heart failure with reduced ejection fraction (HFrEF) without T2DM.

Clinical trial data from the EMPEROR-Reduced trial (2020) showed that when compared to placebo, empagliflozin significantly decreased the risk for HF-related hospitalizations (30%) and cardiac mortality (25%).  Similarly, the DECLARE-TIMI (2019) trial showed that dapagliflozin reduced HF hospitalizations/Cardiovascular death (4.9% vs. 5.8% in the placebo group). 

Common side effects experienced by patients on therapy with SGLT2 inhibitors include:  

  • Urinary tract infections (UTIs) 
  • Genital yeast infections in men and women 
  • Diabetic ketoacidosis 
  • Hypoglycemia 
  • Hypotension 
  • Increase in cholesterol levels 
  • Hyperkalemia 

The use of SGLT2 inhibitors is contraindicated in patients with a history of hypersensitivity to the drug, who are pregnant or breastfeeding, on dialysis, eGFR < 30mL/min/1.73m2 (dapagliflozin), and those who have severe renal impairment.  

 Abarca’s clinical team will continue to communicate updates on new discoveries about the use of SGLT-inhibitors and its impact on Cardiovascular disease.

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*This blog post was written by Erick G. Salas Rodríguez, PharmDc at Abarca Health.

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