From the Guidelines
The most appropriate medication change for this patient is to add dapagliflozin 10 mg orally once daily to the current metformin 500 mg orally twice daily regimen. This patient has stage 3 chronic kidney disease with an eGFR of 35 mL/min/1.73 m², which is within the acceptable range for continuing metformin at the current dose, as indicated by the guidelines from the American Diabetes Association (ADA) and Kidney Disease: Improving Global Outcomes (KDIGO) consensus report 1. According to the most recent guidelines, metformin can be used at reduced doses when eGFR is between 30-45 mL/min/1.73 m², and the patient's current dose is already at a reduced level compared to the maximum recommended dose for her eGFR range 1. Increasing the metformin dose would not be appropriate given her reduced kidney function, as it may increase the risk of lactic acidosis, a potentially life-threatening condition 1. Adding dapagliflozin is beneficial because SGLT2 inhibitors like dapagliflozin have demonstrated significant cardiovascular and kidney protective effects in patients with T2D and CKD, reducing the risk of CKD progression, heart failure hospitalizations, and cardiovascular events 1. The patient's multiple comorbidities (hypertension, dyslipidemia, T2D, and CKD) make her an ideal candidate for an SGLT2 inhibitor, and her current HbA1c of 7.2% indicates that her diabetes control could be improved. Adding dapagliflozin rather than increasing metformin provides both glycemic control and organ protection while minimizing the risk of lactic acidosis that could occur with higher metformin doses in reduced kidney function. Key considerations in managing this patient include monitoring her eGFR regularly, as recommended by the guidelines, to adjust her medication regimen as needed and to minimize the risk of adverse effects 1. Overall, the addition of dapagliflozin to the patient's current metformin regimen is the most appropriate medication change, given the current evidence and guidelines.
From the FDA Drug Label
Metformin hydrochloride tablets are contraindicated in patients with an eGFR less than 30 mL/min/1.73 m 2 Initiation of metformin hydrochloride tablets is not recommended in patients with eGFR between 30 to 45 mL/min/1. 73 m 2. In patients taking metformin hydrochloride tablets whose eGFR falls below 45 mL/min/1. 73 m 2, assess the benefit and risk of continuing therapy.
The patient's eGFR is 35 mL/min/1.73 m2, which is below 45 mL/min/1.73 m2. The most appropriate recommendation is to assess the benefit and risk of continuing metformin therapy.
- Do not increase metformin dose.
- Consider adding dapagliflozin 10 mg orally once daily to metformin 500 mg orally twice daily, but first assess the benefit and risk of continuing metformin therapy. 2
From the Research
Medication Changes for a Patient with Type 2 Diabetes and Chronic Kidney Disease
The patient in question has type 2 diabetes (T2D), hypertension, dyslipidemia, and stage 3 chronic kidney disease (CKD) with an estimated glomerular filtration rate (eGFR) of 35 mL/min/1.73 m2. She is currently taking metformin 500 mg orally twice daily, with an HbA1c of 7.2%. Considering her condition and the American Diabetes Association (ADA) and Kidney Disease: Improving Global Outcomes (KDIGO) consensus report, the following options are available for medication changes:
- Discontinue metformin and initiate dapagliflozin 10 mg orally once daily
- Increase metformin to 1000 mg orally twice daily
- Increase metformin to 1000 mg orally twice daily and initiate dapagliflozin 10 mg orally once daily
- Add dapagliflozin 10 mg orally once daily to metformin 500 mg orally twice daily
Considerations for Dapagliflozin
Dapagliflozin is a sodium-glucose co-transporter-2 (SGLT2) inhibitor that has been shown to be effective in reducing HbA1c levels, body weight, and blood pressure in patients with T2D 3, 4, 5, 6. It works by increasing urinary glucose excretion and reducing blood glucose levels in an insulin-independent manner 7. The addition of dapagliflozin to metformin has been shown to be effective in patients with inadequate glycemic control on metformin alone 5, 6.
Recommendations
Based on the available evidence, adding dapagliflozin 10 mg orally once daily to metformin 500 mg orally twice daily may be the most appropriate option for this patient. This combination has been shown to be effective in reducing HbA1c levels and improving glycemic control in patients with T2D 5, 6. Additionally, dapagliflozin has been shown to have a favorable safety profile, with a low risk of hypoglycemia and no increased risk of major adverse cardiovascular events 4, 6.
Key Points
- Dapagliflozin is a effective add-on therapy to metformin for patients with T2D and inadequate glycemic control 5, 6
- The combination of dapagliflozin and metformin has been shown to reduce HbA1c levels and improve glycemic control 5, 6
- Dapagliflozin has a favorable safety profile, with a low risk of hypoglycemia and no increased risk of major adverse cardiovascular events 4, 6