What is the recommended dosage of empagliflozin (SGLT2 inhibitor) for adults with type 2 diabetes mellitus (T2DM)?

Empagliflozin Dosing in Type 2 Diabetes Mellitus

Start empagliflozin at 10 mg orally once daily in the morning, with or without food, and increase to 25 mg once daily if additional glycemic control is needed. 1, 2

Standard Dosing Regimen

• The recommended starting dose is 10 mg once daily, taken in the morning, with or without food. 1, 2

• The dose may be increased to 25 mg once daily if additional glycemic control is required. 1, 2

• Both the 10 mg and 25 mg doses demonstrate cardiovascular and renal benefits, though the 25 mg dose provides marginally better glycemic control without substantially greater efficacy at lower eGFR levels. 3, 4

• Network meta-analysis of 23 randomized controlled trials (10,518 patients) found that 25 mg performed best when considering HbA1c reduction, fasting plasma glucose lowering, and total adverse events, particularly after long-term use (≥12 weeks). 4

Renal Function-Based Dosing Algorithm

eGFR ≥45 mL/min/1.73 m²

• No dose adjustment required—use either 10 mg or 25 mg once daily. 1, 2
• Both doses are effective for glycemic control and cardiovascular/renal protection. 1

eGFR <45 mL/min/1.73 m²

• Do not initiate empagliflozin for glycemic control, as glucose-lowering efficacy is significantly reduced. 1, 2
• Discontinue empagliflozin if eGFR falls persistently below 45 mL/min/1.73 m². 2
• The medication becomes less effective at lowering glucose when renal function is impaired due to its mechanism of action (inhibiting renal glucose reabsorption). 1

Important Caveat

• SGLT2 inhibitor doses are modified in patients with impaired renal function because the medications are less effective in lowering glucose concentrations when renal function is impaired, rather than because of specific safety concerns. 1
• The cardiovascular benefit of these medications appears to be present down to eGFR of 30 mL/min/1.73 m². 1

Pre-Initiation Assessment

• Assess renal function (eGFR) before initiating empagliflozin. 2
• Assess volume status before initiation, particularly in patients with renal impairment, elderly patients, those with low systolic blood pressure, or those on diuretics. 1, 2
• Correct volume depletion before starting therapy. 1

Dose Adjustments When Adding Empagliflozin

With Insulin or Insulin Secretagogues

• Consider reducing the dose of insulin secretagogue (sulfonylurea) or insulin by approximately 20% when initiating empagliflozin to reduce hypoglycemia risk. 1, 3
• This is particularly important if HbA1c is well-controlled at baseline or if there is a known history of frequent hypoglycemic events. 1

With Diuretics

• Consider stopping or reducing diuretic dose when starting empagliflozin to prevent excessive volume depletion. 1
• Empagliflozin may contribute to intravascular volume contraction through its osmotic diuretic effect. 1

Critical Safety Precautions

Perioperative Management

• Discontinue empagliflozin at least 3 days before planned surgery to prevent postoperative ketoacidosis. 1, 3

Sick Day Rules

• Withhold empagliflozin during acute illness, particularly with reduced oral intake, fever, vomiting, or diarrhea. 3
• Monitor for euglycemic diabetic ketoacidosis, which can occur even with normal blood glucose levels. 1, 3, 2

Monitoring Requirements

• Monitor renal function during therapy. 2
• Consider temporarily discontinuing in settings of reduced oral intake or fluid losses. 2
• Monitor for genital mycotic infections (occur in approximately 6% of patients) and urinary tract infections. 1, 3

Contraindications

• History of serious hypersensitivity reaction to empagliflozin. 1, 2
• Severe renal impairment (eGFR <30 mL/min/1.73 m²), end-stage renal disease, or dialysis. 1, 2
• On dialysis. 1

Common Pitfalls to Avoid

• Do not use empagliflozin for glycemic control if eGFR <45 mL/min/1.73 m², as it will be ineffective due to reduced renal glucose filtration. 1, 2
• Do not forget to reduce insulin or sulfonylurea doses when adding empagliflozin, as this significantly increases hypoglycemia risk. 1, 3
• Do not continue empagliflozin during acute illness without counseling patients to hold the medication, as this increases risk of diabetic ketoacidosis and volume depletion. 1, 3
• Use caution in patients with prior amputation, severe peripheral neuropathy, severe peripheral vascular disease, or active diabetic foot ulcers, as canagliflozin (another SGLT2 inhibitor) has shown increased risk of lower limb complications. 1