From the FDA Drug Label
Use of DAPAGLIFLOZIN TABLETS for glycemic control in patients without established CV disease or CV risk factors is not recommended when eGFR is less than 45 mL/min/1.73 m2
- The threshold for eGFR to initiate a SGLT2 inhibitor like dapagliflozin is less than 45 mL/min/1.73 m2 for patients without established CV disease or CV risk factors, where its use is not recommended.
- There is no mention of a specific threshold for Diabetic Foot Gangrene (DFG) to initiate a SGLT2 inhibitor. 1
From the Research
The threshold for initiating an SGLT2 inhibitor based on estimated glomerular filtration rate (eGFR) is generally 30 mL/min/1.73m², as supported by the most recent study 2. Patients with an eGFR of 30 mL/min/1.73m² or higher can typically start SGLT2 inhibitor therapy, though specific medications within this class have slightly different thresholds. For example, empagliflozin (Jardiance) and dapagliflozin (Farxiga) can be initiated at eGFR ≥30 mL/min/1.73m², while canagliflozin (Invokana) can be started at eGFR ≥45 mL/min/1.73m². Once therapy is initiated, most SGLT2 inhibitors can be continued until dialysis or transplantation, even if eGFR drops below the initiation threshold. This threshold exists because SGLT2 inhibitors work by blocking glucose reabsorption in the proximal tubule of the kidney, which requires adequate kidney function to be effective. As kidney function declines, there are fewer functioning nephrons for the medication to act upon, potentially reducing efficacy. However, recent evidence suggests these medications provide cardiorenal protection even at lower eGFR levels, which is why continuation of therapy is often recommended despite declining kidney function, as seen in studies such as 3 and 4. The benefits of early initiation of SGLT2 inhibitors are also supported by a study using parametric g-formula modeling, which found that initiating SGLT2 inhibitor therapy was associated with a risk reduction in renal deterioration and the development of eGFR <30 mL/min/1.73 m² 2. Key points to consider when initiating SGLT2 inhibitor therapy include:
- The patient's eGFR level, with a threshold of 30 mL/min/1.73m² for most medications
- The presence of diabetic kidney disease or other kidney problems
- The patient's overall health status and medical history
- The potential benefits and risks of SGLT2 inhibitor therapy, including the risk of genital mycotic infections and adverse events related to reduced intravascular volume, as noted in studies such as 5 and 3. In terms of Diabetic Foot Gangrene (DFG), there is no specific threshold for initiating SGLT2 inhibitor therapy, but patients with DFG may benefit from SGLT2 inhibitor therapy due to its cardiorenal protective effects. Overall, the decision to initiate SGLT2 inhibitor therapy should be based on individual patient factors and medical history, with consideration of the potential benefits and risks of therapy.