From the Guidelines
No, it is not recommended to restart dapagliflozin 5 mg for this 87-year-old male patient with acute exacerbation of heart failure with reduced ejection fraction (HFrEF), type 2 diabetes mellitus (T2DM), and a creatinine clearance of 17.34 mL/min. Dapagliflozin is contraindicated in patients with an estimated glomerular filtration rate (eGFR) less than 25 mL/min/1.73m², and this patient's creatinine clearance of 17.34 mL/min falls below this threshold, as indicated in the study by 1. The severely reduced kidney function increases the risk of adverse effects such as acute kidney injury, volume depletion, and electrolyte abnormalities while potentially limiting the medication's efficacy. For management of this patient's HFrEF and T2DM with severe renal impairment, alternative therapies should be considered, such as:
- Guideline-directed medical therapy for heart failure that is appropriate for patients with advanced kidney disease, as suggested by 1 and 1.
- Carefully dosed ACE inhibitors/ARBs, beta-blockers, mineralocorticoid receptor antagonists, and diuretics as needed for volume management.
- For diabetes management, insulin or certain oral agents that can be used safely in severe renal impairment would be more appropriate, as mentioned in 1 and 1. It is essential to prioritize the patient's morbidity, mortality, and quality of life when making treatment decisions, and in this case, alternative therapies are more suitable given the patient's severe renal impairment.
From the FDA Drug Label
• Not recommended for use to improve glycemic control in patients with type 2 diabetes mellitus with an eGFR less than 45 mL/min/1. 73 m2. DAPAGLIFLOZIN TABLETS are likely to be ineffective in this setting based upon its mechanism of action. (1)
The patient has a creatinine clearance of 17.34, which is less than 45 mL/min/1.73 m2. Dapagliflozin is not recommended for use to improve glycemic control in this patient due to the low eGFR. 2
From the Research
Dapagliflozin Treatment in Patients with HFrEF and T2DM
- The study 3 analyzed the effect of dapagliflozin treatment on cardiac, renal function, and safety in patients with HFrEF combined with T2DM, and found that dapagliflozin significantly enhances clinical efficacy, cardiac and renal function, and ambulatory capacity in these patients without an increased risk of adverse effects or outcomes.
- However, the study did not specifically address the use of dapagliflozin in patients with a creatinine clearance of 17.34, which is significantly lower than the average creatinine clearance of the patients in the study.
Dapagliflozin in Patients with Moderate Renal Impairment
- A study 4 found that dapagliflozin did not improve glycemic control in patients with moderate renal impairment, but reduced weight and blood pressure.
- Another study 5 found that dapagliflozin had similar effects on cardio-renal risk factors in patients with T2D with or without renin-angiotensin system inhibitor treatment, including those with moderate renal impairment.
Renal Effects of Dapagliflozin
- A study 6 used a mathematical model to predict the renal effects of dapagliflozin in people with and without diabetes with moderate or severe renal dysfunction, and found that dapagliflozin may reduce interstitial fluid volume and albuminuria in these patients.
- However, the study did not provide direct evidence on the use of dapagliflozin in patients with a creatinine clearance of 17.34.
Assessment of Glomerular Filtration Rate (GFR)
- A study 7 found that estimating equations for GFR, such as the Cockcroft-Gault equation, may not be accurate in critically ill patients with acute kidney injury, and that direct measurement of GFR using infusion clearance of chromium-ethylenediaminetetraacetic acid (51Cr-EDTA) may be more accurate.
- However, this study did not address the use of dapagliflozin in patients with HFrEF and T2DM, and the results may not be directly applicable to this patient population.
Considerations for Restarting Dapagliflozin
- Given the patient's acute exacerbation of HFrEF and T2DM, and creatinine clearance of 17.34, careful consideration should be given to the potential benefits and risks of restarting dapagliflozin 5 mg, including the potential for improved cardiac and renal function, as well as the potential for adverse effects such as hypoglycemia, urinary tract infection, and gastrointestinal adverse effects 3, 4, 5, 6.