From the Guidelines
For patients with impaired renal function, the typical starting dose of SGLT2 inhibitors, such as canagliflozin, dapagliflozin, and empagliflozin, should be initiated at the lowest dose tested in CV and renal outcomes trials, which are 100 mg PO daily for canagliflozin, 10 mg PO daily for dapagliflozin, and 10 mg PO daily for empagliflozin, with dose adjustments based on eGFR levels, as recommended in the 2020 expert consensus decision pathway on novel therapies for cardiovascular risk reduction in patients with type 2 diabetes 1.
Key Considerations for Dosing
- Canagliflozin: 100 mg PO daily for patients with eGFR ≥45 mL/min/1.73m², with a maximum dose of 100 mg daily for patients with eGFR 30-44 mL/min/1.73m², and initiation not recommended for patients with eGFR <30 mL/min/1.73m² 1.
- Dapagliflozin: 10 mg PO daily for patients with eGFR ≥45 mL/min/1.73m², with initiation not recommended for patients with eGFR <25 mL/min/1.73m², and may continue 10 mg daily if tolerated for kidney and CV benefit until dialysis 1.
- Empagliflozin: 10 mg PO daily for patients with eGFR ≥45 mL/min/1.73m², with use not recommended for patients with eGFR <30 mL/min/1.73m² for glycemic control, and initiation not recommended with eGFR <20 mL/min/1.73m² for HF 1.
Rationale for Dosing Recommendations
The dosing recommendations for SGLT2 inhibitors in patients with impaired renal function are based on the reduced efficacy of these medications in patients with decreased kidney function, as well as the potential for adverse effects such as volume depletion and acute kidney injury 1.
Monitoring and Safety Considerations
Patients with impaired renal function may require careful monitoring of kidney function, blood pressure, and hydration status when using SGLT2 inhibitors, and dose adjustments should be made based on eGFR levels and individual patient response 1.
From the FDA Drug Label
The recommended starting dosage in adults and pediatric patients aged 10 years and older with type 2 diabetes mellitus is 100 mg orally once daily, taken before the first meal of the day to improve glycemic control. Assess renal function before initiating and as clinically indicated. Dosage adjustments for patients with renal impairment may be required (2.3). The recommended dose of JARDIANCE is 10 mg once daily, taken in the morning, with or without food (2.1) Assess renal function before initiating JARDIANCE. Do not initiate JARDIANCE if eGFR is below 45 mL/min/1.73 m2 (2.2)
The typical starting dose of SGLT2 inhibitors, such as canagliflozin (Invokana) and empagliflozin (Jardiance), for patients with impaired renal function is:
- Canagliflozin (Invokana): 100 mg orally once daily
- Empagliflozin (Jardiance): 10 mg once daily Key points:
- Assess renal function before initiating SGLT2 inhibitors.
- Dosage adjustments may be required for patients with renal impairment.
- Do not initiate empagliflozin (Jardiance) if eGFR is below 45 mL/min/1.73 m2 2
- Canagliflozin (Invokana) is not recommended for use to improve glycemic control in patients with type 2 diabetes mellitus with an eGFR less than 30 mL/min/1.73 m2 3
From the Research
SGLT2 Inhibitor Starting Dose
- The typical starting dose of SGLT2 inhibitors, such as canagliflozin, dapagliflozin, and empagliflozin, is not explicitly stated in the provided studies for patients with impaired renal function.
- However, it is mentioned that these medications can be used in patients with renal impairment, with empagliflozin showing safety in type 2 diabetics with renal impairment 4.
- The studies suggest that SGLT2 inhibitors can be effective in improving glycaemic control, promoting weight loss, and lowering blood pressure in patients with type 2 diabetes 5, 6, 7.
- It is also noted that SGLT2 inhibitors may have benefits in patients with cardiovascular disease, heart failure, or chronic kidney disease, including those without diabetes 6, 8.
Dosage Considerations
- The dosage of SGLT2 inhibitors may need to be adjusted in patients with impaired renal function, although the specific starting dose is not provided in the studies.
- Clinicians should be aware of the potential side effects of SGLT2 inhibitors, such as genital tract infections, lower leg amputations, electrolyte disturbances, and bone fractures, and monitor patients accordingly 7.
- SGLT2 inhibitors can be used as a single treatment or in combination with other anti-diabetic medications, and may be beneficial as an adjunct medication in addition to metformin in patients with a history of cardiovascular or renal disease 5, 7.