What is the role of Empagliflozin (Jardiance) in managing type 2 diabetes mellitus?

From the Guidelines

Empagliflozin (Jardiance) is a highly recommended medication for managing type 2 diabetes, particularly in patients with established cardiovascular disease, due to its significant cardiovascular benefits, including reducing the risk of heart failure hospitalizations and cardiovascular death, as demonstrated in the EMPA-REG OUTCOME trial 1.

Key Benefits and Considerations

• Empagliflozin works by increasing glucose excretion through the kidneys and is typically prescribed at a starting dose of 10 mg once daily, with possible increase to 25 mg daily if needed for better glycemic control.
• Beyond lowering blood glucose, Empagliflozin offers additional benefits including modest weight loss (typically 2-3 kg), blood pressure reduction, and potential kidney protection.
• Common side effects include genital yeast infections and increased urination, while more serious but rare effects include diabetic ketoacidosis and urinary tract infections.
• Patients should maintain adequate hydration while taking this medication and temporarily discontinue it during periods of reduced oral intake or acute illness.
• Empagliflozin should not be used in patients with type 1 diabetes, severe kidney impairment (eGFR <30 ml/min/1.73m²), or those on dialysis, as indicated by studies such as the CREDENCE trial and guidelines from Diabetes Care 1.

Clinical Evidence and Guidelines

• The EMPA-REG OUTCOME trial, a randomized, double-blind trial, assessed the effect of empagliflozin versus placebo on cardiovascular outcomes in 7,020 patients with type 2 diabetes and existing cardiovascular disease, showing a reduction in the composite outcome of MI, stroke, and cardiovascular death by 14% and cardiovascular death by 38% 1.
• The Canagliflozin Cardiovascular Assessment Study (CANVAS) Program and the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trial also support the use of SGLT2 inhibitors like empagliflozin for reducing cardiovascular and renal events in patients with type 2 diabetes and CKD 1.

Patient Selection and Monitoring

• The selection of empagliflozin may depend on comorbidity and CKD stage, with SGLT2 inhibitors being more useful for patients at high risk of CKD progression.
• Empagliflozin can be started with eGFR >30 mL/min/1.73 m², though pivotal trials have demonstrated benefit in subgroups with low eGFR.
• Regular monitoring of kidney function, blood glucose, and cardiovascular risk factors is essential for patients on empagliflozin, as recommended by guidelines from Diabetes Care 1.

From the FDA Drug Label

JARDIANCE is 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 role of Empagliflozin (Jardiance) in managing type 2 diabetes mellitus is:

• Improving glycemic control: as an adjunct to diet and exercise in adults with type 2 diabetes mellitus.
• Reducing cardiovascular risk: to reduce the risk of cardiovascular death in adult patients with type 2 diabetes mellitus and established cardiovascular disease 2, 2, 2.

From the Research

Role of Empagliflozin in Managing Type 2 Diabetes Mellitus

Empagliflozin, also known as Jardiance, plays a significant role in managing type 2 diabetes mellitus (T2DM) due to its unique mechanism of action as a sodium-glucose cotransporter 2 (SGLT2) inhibitor. This class of drugs works by promoting the excretion of glucose in the urine, thereby lowering plasma glucose levels independently of β-cell function 3.

Clinical Benefits

The clinical benefits of empagliflozin include:

• Reduction in cardiovascular morbidity and mortality in patients with T2DM and established cardiovascular disease, as demonstrated in the EMPA-REG OUTCOME trial 4, 3, 5, 6.
• Improvement in glycemic control, with significant reductions in glycated hemoglobin (HbA1c) levels 3, 7.
• Modest reductions in body weight and blood pressure, contributing to an overall favorable effect on non-glycemic outcomes 3, 5.
• Reduced risk of hospitalization for heart failure and renal adverse events 6.

Safety and Tolerability

Empagliflozin is generally well-tolerated, with a low inherent risk of hypoglycemia due to its insulin-independent mechanism of action 3, 5. However, it is associated with a higher rate of genital mycotic infections compared to placebo 3, 6. The adverse event profile of empagliflozin is consistent across different patient populations, including those with chronic kidney disease 4.

Dosage and Administration

The efficacy and safety of empagliflozin at different doses have been evaluated in clinical trials. A network meta-analysis suggested that a daily dose of 25 mg performs best among different doses in terms of lowering HbA1c and fasting plasma glucose levels, while also considering safety 7.

Patient Selection

Empagliflozin is a valuable treatment option for patients with T2DM, particularly those at high cardiovascular risk who require additional antidiabetic medication to achieve their glycemic goals 5, 6. However, careful consideration of individual patient characteristics, such as renal function and history of genital mycotic infections, is necessary to ensure appropriate use.