What are the guidelines for using SGLT2 (Sodium-Glucose Linked Transporter 2) inhibitors, such as empagliflozin (Empagliflozin), in patients with type 2 diabetes and established cardiovascular disease or high risk of cardiovascular events?

From the Guidelines

SGLT2 inhibitors like empagliflozin are strongly recommended for patients with type 2 diabetes who have established cardiovascular disease or are at high risk for cardiovascular events, and can be used in patients with an eGFR as low as 20 mL/min/1.73 m² and UACR >200 mg/g creatinine to reduce CKD progression and cardiovascular events. These medications should be considered as second-line therapy after metformin, or even as first-line therapy in patients with atherosclerotic cardiovascular disease, heart failure, or chronic kidney disease. The typical starting dose for empagliflozin is 10 mg once daily, which can be increased to 25 mg daily if needed and tolerated. Other SGLT2 inhibitors with proven cardiovascular benefits include dapagliflozin (starting at 5-10 mg daily) and canagliflozin (starting at 100 mg daily, maximum 300 mg) 1.

Key Considerations

• SGLT2 inhibitors should be used with caution in patients with estimated glomerular filtration rates below 45 ml/min/1.73m², and are generally recommended for use in patients with eGFR ≥20 mL/min/1.73 m² and UACR >200 mg/g creatinine 1.
• Patients should be monitored for side effects including genital mycotic infections, urinary tract infections, volume depletion, and rare but serious diabetic ketoacidosis 1.
• SGLT2 inhibitors work by preventing glucose reabsorption in the kidneys, leading to increased urinary glucose excretion, which reduces hyperglycemia and provides cardiovascular protection through multiple mechanisms including reduced blood pressure, decreased arterial stiffness, weight loss, and improved cardiac metabolism.

Dosage and Administration

• The typical starting dose for empagliflozin is 10 mg once daily, which can be increased to 25 mg daily if needed and tolerated.
• Dapagliflozin can be started at 5-10 mg daily, and canagliflozin can be started at 100 mg daily, with a maximum dose of 300 mg.

Evidence Base

• The recommendation to use SGLT2 inhibitors in patients with type 2 diabetes and established cardiovascular disease or high risk of cardiovascular events is based on evidence from large randomized controlled trials, including the CREDENCE and DAPA-CKD trials 1.
• The use of SGLT2 inhibitors in patients with eGFR ≥20 mL/min/1.73 m² and UACR >200 mg/g creatinine is supported by subgroup analyses from the DAPA-CKD and EMPEROR heart failure trials 1.

From the FDA Drug Label

JARDIANCE is a sodium-glucose co-transporter 2 (SGLT2) inhibitor indicated: as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus, to reduce the risk of cardiovascular death in adult patients with type 2 diabetes mellitus and established cardiovascular disease. The recommended dose of JARDIANCE is 10 mg once daily, taken in the morning, with or without food Assess renal function before initiating JARDIANCE. Do not initiate JARDIANCE if eGFR is below 45 mL/min/1.73 m2 Discontinue JARDIANCE if eGFR falls persistently below 45 mL/min/1.73 m2

The guidelines for using SGLT2 inhibitors, such as empagliflozin, in patients with type 2 diabetes and established cardiovascular disease or high risk of cardiovascular events are:

• Dose: 10 mg once daily, taken in the morning, with or without food, which may be increased to 25 mg once daily.
• Renal function assessment: Assess renal function before initiating empagliflozin and do not initiate if eGFR is below 45 mL/min/1.73 m2.
• Contraindications: Severe renal impairment, end-stage renal disease, or dialysis.
• Warnings and precautions: Hypotension, ketoacidosis, acute kidney injury and impairment in renal function, urosepsis and pyelonephritis, hypoglycemia, genital mycotic infections, hypersensitivity reactions, and increased LDL-C. 2

From the Research

Guidelines for Using SGLT2 Inhibitors

The guidelines for using SGLT2 inhibitors, such as empagliflozin, in patients with type 2 diabetes and established cardiovascular disease or high risk of cardiovascular events are as follows:

• SGLT2 inhibitors are recommended for patients with type 2 diabetes who have established cardiovascular disease or are at high risk of cardiovascular events 3, 4.
• These inhibitors have been shown to reduce the risk of major adverse cardiovascular events, including cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke 3, 4.
• SGLT2 inhibitors also have renoprotective effects, slowing the progression of kidney disease and reducing the risk of clinically relevant renal events 3, 5.
• The adverse-event profile of SGLT2 inhibitors in patients with impaired kidney function at baseline is similar to that reported in the overall trial population 3.

Patient Selection

When selecting patients for SGLT2 inhibitor therapy, consider the following:

• Patients with type 2 diabetes and established cardiovascular disease or high risk of cardiovascular events are ideal candidates 3, 4.
• Patients with chronic kidney disease (CKD) or heart failure may also benefit from SGLT2 inhibitor therapy 5, 6.
• Estimated glomerular filtration rate (eGFR) should be considered when initiating SGLT2 inhibitor therapy, as these drugs are most effective when eGFR is >60 ml/min/1.73m² 7.

Monitoring and Contraindications

• Monitor patients for adverse events, such as mycotic genital infections, and adjust therapy as needed 3, 4.
• SGLT2 inhibitors are contraindicated in patients with a history of diabetic ketoacidosis or those at risk of diabetic ketoacidosis 7.
• GLP-1 receptor agonists, often used in conjunction with SGLT2 inhibitors, are contraindicated in patients with a history of medullary thyroid cancer and should be used with caution in patients with a history of pancreatitis 7.