What is the role of Sodium-Glucose Linked Transporter 2 (SGLT2) inhibitors?

From the Guidelines

SGLT2 inhibitors should be used to treat people with type 2 diabetes and increased cardiovascular risk or established cardiovascular disease to prevent the development of incident heart failure. This recommendation is based on the most recent and highest quality study, which suggests that SGLT2 inhibitors reduce the risk of heart failure hospitalizations and cardiovascular mortality in people with type 2 diabetes, regardless of prior history of heart failure 1. The key benefits of SGLT2 inhibitors include:

• Reducing the risk of heart failure hospitalizations by 33-35% as seen in the EMPA-REG OUTCOME trial and the CANVAS Program 1
• Reducing cardiovascular mortality and hospitalization for heart failure by 17% as seen in the DECLARE-TIMI 58 study 1
• Promoting modest weight loss and reducing blood pressure
• Reducing the progression of kidney disease However, it is essential to monitor patients for potential side effects, including:
• Genital mycotic infections
• Urinary tract infections
• Volume depletion
• Diabetic ketoacidosis, a rare but serious side effect SGLT2 inhibitors work by blocking sodium-glucose cotransporter 2 proteins in the proximal tubule of the kidney, preventing glucose reabsorption and allowing it to be eliminated through urine, which reduces blood glucose levels independently of insulin action. Common SGLT2 inhibitors include empagliflozin (Jardiance), dapagliflozin (Farxiga), canagliflozin (Invokana), and ertugliflozin (Steglatro), typically taken once daily. Overall, the use of SGLT2 inhibitors in people with type 2 diabetes and increased cardiovascular risk or established cardiovascular disease is a crucial treatment approach to reduce cardiovascular disease and heart failure outcomes, as supported by the latest evidence 1.

From the FDA Drug Label

12 CLINICAL PHARMACOLOGY 12. 1 Mechanism of Action Sodium-glucose co-transporter 2 (SGLT2) is the predominant transporter responsible for reabsorption of glucose from the glomerular filtrate back into the circulation. Empagliflozin is an inhibitor of SGLT2 By inhibiting SGLT2, empagliflozin reduces renal reabsorption of filtered glucose and lowers the renal threshold for glucose, and thereby increases urinary glucose excretion.

• SGLT2 Inhibition: Empagliflozin is an inhibitor of SGLT2, which is the predominant transporter responsible for reabsorption of glucose from the glomerular filtrate back into the circulation 2.
• Mechanism of Action: By inhibiting SGLT2, empagliflozin reduces renal reabsorption of filtered glucose and lowers the renal threshold for glucose, increasing urinary glucose excretion.
• Key Points:
  • Empagliflozin inhibits SGLT2
  • Inhibition of SGLT2 reduces renal reabsorption of glucose
  • Increases urinary glucose excretion 2

From the Research

SGLT2 Inhibitors and Their Effects

• SGLT2 inhibitors, such as empagliflozin, have been shown to reduce cardiovascular morbidity and mortality in patients with type 2 diabetes mellitus and established cardiovascular disease 3.
• These inhibitors work by reducing urinary glucose excretion, which decreases with declining renal function, resulting in less potency for glucose lowering in patients with kidney disease 3.
• The use of SGLT2 inhibitors has been associated with a reduced risk of major adverse cardiovascular events, hospitalization for heart failure, and kidney outcomes in patients with type 2 diabetes 4.

Chronic Kidney Disease and SGLT2 Inhibitors

• There is an unmet need for effective treatment of chronic kidney disease (CKD) that slows disease progression, prevents development of end-stage kidney disease and cardiovascular disease, and prolongs survival of patients with CKD 5.
• SGLT2 inhibitors have been shown to reduce the risk of CKD progression in patients with and without type 2 diabetes, and have been associated with a reduced risk of all-cause mortality in patients with CKD 5.
• The use of SGLT2 inhibitors in patients with CKD has been recommended as a promising therapeutic option to slow disease progression 5.

Clinical Practice Guidelines for SGLT2 Inhibitors

• Clinical practice guidelines have been developed for the use of SGLT2 inhibitors in adults with type 2 diabetes, taking into account the patient's individual risk for cardiovascular and kidney outcomes 6.
• The guidelines recommend the use of SGLT2 inhibitors in patients with established cardiovascular disease or chronic kidney disease, and suggest that they may be considered in patients with multiple cardiovascular risk factors 6.
• The guidelines also emphasize the importance of individualized treatment and shared decision-making between clinicians and patients 6.

Comprehensive Cardiovascular and Renal Protection

• Comprehensive cardiovascular and renal protection is essential in patients with type 2 diabetes, and involves the intensification of lifestyle changes and the prescription of drugs that have been shown to reduce complications 7.
• SGLT2 inhibitors have been recognized as cardiovascular protective drugs, and are recommended to be used at the same level as statins, acetylsalicylic acid, or renin angiotensin system inhibitors 7.
• A global control of cardiovascular risk factors, including weight management and education of patients, is also important in the management of patients with type 2 diabetes 7.