Which SGLT-2 (sodium-glucose cotransporter-2) inhibitor to initiate in a 75-year-old black male with an Hemoglobin A1c (HbA1c) of 6.5% and impaired renal function, specifically a glomerular filtration rate (GFR) of 53 mL/min/1.73m²?

From the Guidelines

For a 75-year-old Black male with an A1c of 6.5% and eGFR of 53 mL/min/1.73m², canagliflozin (Invokana) would be an appropriate SGLT-2 inhibitor to initiate, given its suitability for patients with moderate renal impairment and demonstrated cardiovascular benefits, as noted in the 2020 expert consensus decision pathway on novel therapies for cardiovascular risk reduction in patients with type 2 diabetes 1. The recommended starting dose is 100 mg once daily. This medication can be used with an eGFR as low as 30 mL/min/1.73m², but the dose should be adjusted to a maximum of 100 mg daily for patients with an eGFR between 30-59 mL/min/1.73m², as indicated in the study 1. Key considerations for the use of SGLT-2 inhibitors in patients with reduced kidney function include:

• Monitoring for potential side effects such as genital mycotic infections, urinary tract infections, and volume depletion
• Counseling the patient about proper genital hygiene and adequate hydration
• Being aware of the decreased glycemic efficacy of SGLT-2 inhibitors in patients with severely reduced kidney function, although their renal and cardiovascular benefits may still be beneficial, as discussed in the 2022 diabetes management in chronic kidney disease consensus report 1
• Considering the patient's overall clinical profile, including history of prior amputation, severe peripheral arterial disease, or active diabetic foot ulcers, which may prompt caution with canagliflozin, as noted in the 2020 expert consensus decision pathway 1. Given the patient's moderate renal impairment, canagliflozin is a suitable option, and its use is supported by recent studies, including the 2022 study on cognitive impairment and type 2 diabetes mellitus, which highlights the benefits of SGLT-2 inhibitors in patients with type 2 diabetes 1.

From the FDA Drug Label

6 Renal Impairment The efficacy and safety of JARDIANCE were evaluated in a study of patients with mild and moderate renal impairment [see Clinical Studies (14.1)]. In this study, 195 patients exposed to JARDIANCE had an eGFR between 60 and 90 mL/min/1.73 m2, 91 patients exposed to JARDIANCE had an eGFR between 45 and 60 mL/min/1. 73 m2 and 97 patients exposed to JARDIANCE had an eGFR between 30 and 45 mL/min/1.73 m2. The glucose lowering benefit of JARDIANCE 25 mg decreased in patients with worsening renal function.

The patient has a GFR of 53, which falls into the category of moderate renal impairment.

• Empagliflozin may be considered as it has been evaluated in patients with moderate renal impairment.
• However, the glucose lowering benefit of empagliflozin decreases in patients with worsening renal function. Given the patient's renal function and A1c of 6.5, empagliflozin may be a suitable option, but it is essential to monitor renal function and adjust the dose as needed 2.
• It is also crucial to consider the potential risks of renal impairment, volume depletion, and urinary tract infections associated with empagliflozin use in patients with moderate renal impairment.
• The decision to start empagliflozin should be made with caution, taking into account the patient's overall clinical profile and potential benefits and risks.

From the Research

SGLT-2 Inhibitors for a 75-Year-Old Black Male with A1C of 6.5 and GFR of 53

• The patient's GFR of 53 indicates mild chronic kidney disease (CKD) 3, 4, 5, 6.
• SGLT-2 inhibitors, such as dapagliflozin, canagliflozin, and empagliflozin, are effective in lowering hemoglobin A1C and fasting plasma glucose in patients with type 2 diabetes mellitus (T2DM) and CKD 7, 4, 5, 6.
• However, the glucose-lowering efficacy of SGLT-2 inhibitors is decreased in patients with CKD compared to those without CKD 3, 6.
• SGLT-2 inhibitors have been shown to have renal benefits, including a reduction in albuminuria and a reduced risk of progression to albuminuria, even in patients with CKD 4, 5, 6.
• The choice of SGLT-2 inhibitor should be based on the patient's individual characteristics, such as renal function, and the presence of other comorbidities 3, 4, 5, 6.
• Empagliflozin has been shown to have cardiovascular benefits, including a reduction in cardiovascular mortality and heart failure hospitalizations, in patients with T2DM and established cardiovascular disease 5.
• Canagliflozin and dapagliflozin have also been shown to have cardiovascular benefits, although the evidence is not as extensive as for empagliflozin 7, 4, 5.

Considerations for Initiating SGLT-2 Inhibitor Therapy

• The patient's GFR of 53 indicates that a reduced dose of the SGLT-2 inhibitor may be necessary 3, 6.
• The patient's A1C of 6.5 indicates that the patient has relatively well-controlled diabetes, and the SGLT-2 inhibitor may be used to further improve glycemic control 7, 4, 5, 6.
• The patient's age and presence of CKD should be taken into consideration when initiating SGLT-2 inhibitor therapy, as older adults and those with CKD may be at increased risk of adverse effects 3, 4, 5, 6.