Recommendations

Assess all individuals with T2DM for established CVD and/or CKD or risk for them using standard diagnostic criteria. Initate SGLT2i in those with established CVD and/or CKD and in those with three or more CVD and/or CKD risk factors without established CVD and/or CKD.

Assess all CKD patients for risk of progression. Those with stages 3 - 5 CKD and high progression risk (urine albumin-to-creatinine ratio: UACR > 300 mg/g) should be considered for SGLT2i

Adults with CKD and heart failure or eGFR ≥ 20 mL/min/1.73m² with UACR ≥ 200 mg/g should be treated with an SGLT2 inhibitor.

Adults with eGFR ≥ 20 - 45 mL/min/1.73m² with UACR < 200 mg/g should be treated with an SGLT2 inhibitor.

Do not initiate SGLT2i if eGFR is below 20 mL/min/1.73m² but continue SGLT2i if the patient is already on it.

Regular monitoring is also essential for patients with CKD who are receiving SGLT2is.

Patients with a history of AKI, hypotension, or dehydration should be monitored closely if SGLT2 inhibitors are used.

Patients on SGLT2is should have their eGFR and serum creatinine levels monitored before initiating therapy and periodically thereafter to assess renal function. Close monitoring is recommended in patients with eGFR < 60 mL/min/1.73m².

Patients should be monitored for signs and symptoms of volume depletion, including orthostatic hypotension and electrolyte abnormalities, such as hyponatremia and hyperkalemia.

Assess for risk factors for AKI while on SGLT2is.

Use SGLT2i with caution in those with a history of genital or urinary tract infections.

Counseling for patients with regards genital infections, and volume status is recommended for those on SGLT2is.

Patients should be advised to withhold SGLT2is during an acute illness that can lead to dehydration.

Drug-to-drug interactions should be considered when prescribing SGLT2is with loop diuretics, ACEIs, ARBs, other anti-DM medications, NSAIDs, and statins.

Dosage adjustments are necessary. The recommended dosage adjustments for SGLT2is in patients with impaired kidney function are as follows:

口 Dapagliflozin is 10 mg once daily, and it should not be used in patients with an eGFR less than 25 mL/min/1.73m².

口 The recommended starting dose of Empagliflozin is 10 mg once daily, and it should not be used in patients with an eGFR less than 20 mL/min/1.73m².

口 The recommended starting dose of Canagliflozin is 100 mg once daily, and it should not be used in patients with an eGFR less than 45 mL/min/1.73 m².

Future directions and ongoing research in this field.

More research is needed to establish the role of SGLT2is therapy in specific populations with kidney diseases, such as kidney transplant recipients, those with lower grades of proteinuria (A2, e.g. those with chronic interstitial nephritis or CKD of unknown etiology), and those with lower eGFR.

Saudi cost-benefit analyses need to be undertaking to define the place of SGLT2is in standard treatment algorithms.

More research studies are needed to highlight the drug-drug interaction of SGLT2is in different population.