Which is more potent, Empagliflozin (SGLT2 inhibitor) or Dapagliflozin (SGLT2 inhibitor)?

From the Guidelines

Empagliflozin is more potent than dapagliflozin as an SGLT2 inhibitor, with a greater effect on reducing HbA1c levels and urinary glucose excretion, as well as a more significant reduction in hospitalization for heart failure and cardiovascular death, as demonstrated in the EMPA-REG OUTCOME trial 1 and the 2024 standards of care in diabetes 1.

Key Points

• Empagliflozin has approximately 2.5 times higher selectivity for SGLT2 over SGLT1 compared to dapagliflozin, which translates to greater glucose-lowering efficacy at equivalent doses.
• In clinical practice, empagliflozin is typically prescribed at 10-25mg once daily, while dapagliflozin is prescribed at 5-10mg once daily.
• The higher potency of empagliflozin is reflected in its slightly greater effect on reducing HbA1c levels (approximately 0.1-0.2% more reduction) and urinary glucose excretion.
• The EMPA-REG OUTCOME trial demonstrated a significant 35% reduction in hospitalization for heart failure with empagliflozin compared to placebo 1.
• The DAPA-HF trial showed a 26% reduction in the primary endpoint of worsening heart failure or cardiovascular death with dapagliflozin compared to placebo 1.

Comparison of SGLT2 Inhibitors

• Both empagliflozin and dapagliflozin are effective SGLT2 inhibitors with similar safety profiles and cardiovascular benefits when used at their recommended therapeutic doses for treating type 2 diabetes.
• However, empagliflozin has a more significant effect on reducing hospitalization for heart failure and cardiovascular death, as demonstrated in the EMPA-REG OUTCOME trial 1 and the 2024 standards of care in diabetes 1.

Clinical Implications

• In people with type 2 diabetes and established HFpEF or HFrEF, an SGLT2 inhibitor with proven benefit in this patient population, such as empagliflozin, is recommended to reduce the risk of worsening heart failure and cardiovascular death 1.
• The choice of SGLT2 inhibitor should be based on individual patient characteristics, comorbidities, and concomitant medications, as well as the specific benefits and risks associated with each medication.

From the FDA Drug Label

12 CLINICAL PHARMACOLOGY

1. 2 Pharmacodynamics Urinary Glucose Excretion In patients with type 2 diabetes mellitus, urinary glucose excretion increased immediately following a dose of empagliflozin and was maintained at the end of a 4-week treatment period averaging at approximately 64 grams per day with 10 mg empagliflozin and 78 grams per day with 25 mg empagliflozin once daily

12 CLINICAL PHARMACOLOGY

1. 2 Pharmacodynamics General Dapagliflozin doses of 5 or 10 mg per day in patients with type 2 diabetes mellitus for 12 weeks resulted in excretion of approximately 70 grams of glucose in the urine per day.

The potency of Empagliflozin and Dapagliflozin can be compared based on their effects on urinary glucose excretion.

• Empagliflozin at a dose of 25 mg once daily results in an average urinary glucose excretion of 78 grams per day.
• Dapagliflozin at a dose of 10 mg per day results in an average urinary glucose excretion of 70 grams per day. Based on these values, Empagliflozin at a dose of 25 mg appears to be more potent than Dapagliflozin at a dose of 10 mg in terms of increasing urinary glucose excretion 2 3.

From the Research

Comparison of Empagliflozin and Dapagliflozin

• Both Empagliflozin and Dapagliflozin are SGLT2 inhibitors used in the treatment of type 2 diabetes.
• They work by inhibiting the reabsorption of glucose in the kidney, increasing urinary glucose excretion, and reducing blood glucose levels 4, 5, 6.

Efficacy in Glycemic Control

• Empagliflozin has been shown to reduce HbA1c levels and improve glycemic control in patients with type 2 diabetes 5, 6, 7.
• Dapagliflozin also reduces HbA1c levels and improves glycemic control, but to a lesser extent compared to Empagliflozin in some studies 4, 7.
• A 52-week prospective observational study found that Empagliflozin was more effective in reducing HbA1c and improving cardiometabolic parameters compared to Dapagliflozin 7.

Cardiovascular Outcomes

• Empagliflozin has been shown to reduce the risk of cardiovascular death, all-cause mortality, and hospitalization for heart failure in patients with type 2 diabetes and cardiovascular disease 5.
• Dapagliflozin has also been found to have cardiovascular benefits, including a reduced risk of atrial fibrillation compared to Empagliflozin 8.
• A network meta-analysis found that both Empagliflozin and Dapagliflozin had comparable efficacy in preventing most cardiovascular outcomes, but Dapagliflozin was superior in preventing atrial fibrillation 8.

Potency Comparison

• Based on the available evidence, Empagliflozin appears to be more potent than Dapagliflozin in terms of glycemic control and cardiovascular outcomes 5, 7.
• However, Dapagliflozin may have a lower risk of atrial fibrillation compared to Empagliflozin, which could be an important consideration in treatment decisions 8.