What is the relationship between Farxiga (dapagliflozin) and increased creatinine levels, indicating impaired renal function?

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From the Guidelines

Farxiga (dapagliflozin) can cause a temporary increase in serum creatinine levels, which is generally expected and not a cause for immediate concern in most patients, as it provides long-term kidney protection and reduces cardiovascular events, as shown in the 2022 guideline for chronic kidney disease and risk management in diabetes 1. When starting Farxiga, patients typically experience a 10-15% increase in creatinine levels within the first few weeks of treatment, which usually stabilizes thereafter. This occurs because Farxiga works by blocking glucose reabsorption in the kidneys and altering renal hemodynamics, which can reduce glomerular filtration rate initially. However, long-term studies suggest that despite this initial increase, Farxiga actually provides kidney protection over time for many patients with type 2 diabetes or heart failure, with benefits seen in patients with an eGFR ≥20 mL/min/1.73 m² and urine albumin ranging from normal to 200 mg/g creatinine 1. Some key points to consider when prescribing Farxiga include:

  • Regular kidney function monitoring, especially in patients with pre-existing kidney disease
  • Staying well-hydrated while taking Farxiga
  • Reporting symptoms like severe dizziness, extreme fatigue, or significantly reduced urination, which could indicate more serious kidney issues requiring medical attention
  • Temporarily discontinuing the medication if creatinine increases more than 30% from baseline or exceeds safe thresholds (typically 4.0 mg/dL) The use of SGLT2 inhibitors, such as Farxiga, is recommended to reduce CKD progression and cardiovascular events in patients with type 2 diabetes and diabetic kidney disease, with an eGFR ≥20 mL/min/1.73 m² and urine albumin ranging from normal to 200 mg/g creatinine, as stated in the 2022 guideline 1. Additionally, the 2021 HFA/ESC guidelines on HF management recommend the use of SGLT2 inhibitors, such as Farxiga, as core treatments suitable for all patients with heart failure with reduced ejection fraction, due to their unique benefits and favorable safety profile 1.

From the FDA Drug Label

Dapagliflozin can cause intravascular volume depletion which may sometimes manifest as symptomatic hypotension or acute transient changes in creatinine.

Dapagliflozin, also known as Farxiga, may cause an increase in creatinine levels due to intravascular volume depletion. Key points to consider:

  • Volume depletion may manifest as symptomatic hypotension or acute transient changes in creatinine.
  • Patients with impaired renal function (eGFR less than 60 mL/min/1.73 m2), elderly patients, or patients on loop diuretics may be at increased risk for volume depletion or hypotension.
  • It is essential to monitor for signs and symptoms of hypotension and renal function after initiating DAPAGLIFLOZIN TABLETS therapy 2.

From the Research

Farxiga and Creatinine Increase

  • The effect of Farxiga (dapagliflozin) on creatinine levels is not directly addressed in the provided studies, but its impact on kidney function can be inferred from the available data 3, 4, 5.
  • A study published in The Lancet found that 6-week treatment with dapagliflozin induced an acute and reversible decline in measured glomerular filtration rate (mGFR) in patients with chronic kidney disease without diabetes 3.
  • Another study compared the effects of dapagliflozin and DPP-4 inhibitors on glucose variability and metabolic parameters in patients with type 2 diabetes mellitus on insulin, and found that dapagliflozin may provide favorable effects on metabolism, including reductions in body mass index and albuminuria 4.
  • However, the study also noted that combination therapy of dapagliflozin and insulin was not superior in glucose fluctuation to DPP-4 inhibitors on insulin 4.
  • A multicentre retrospective study found that elderly patients with type 2 diabetes initiating dapagliflozin had a lower probability of achieving individualized HbA1c targets than those initiating DPP-4 inhibitors, but displayed better improvements in extra-glycaemic endpoints, including reductions in body weight and blood pressure 5.
  • Overall, while the provided studies do not directly address the effect of Farxiga on creatinine levels, they suggest that dapagliflozin may have both positive and negative effects on kidney function, depending on the context and population being studied 3, 4, 5.

Related Questions

What is the appropriate treatment to add for a 71-year-old Hispanic male with Chronic Kidney Disease (CKD) stage IIIa and hyperglycemia, currently on Farxiga (Dapagliflozin) 10 mg daily, with an increased Hemoglobin A1c (HbA1c) from 6.8% to 8.0%?
Can I add dapagliflozin (Farxiga) to a type 2 diabetic patient with estimated glomerular filtration rate ≥45 mL/min/1.73 m², no recurrent genital or urinary‑tract infections, not pregnant or breastfeeding, and currently on prednisone for an acute gout flare, to improve A1C and lower uric acid?
Should a SGLT2 inhibitor be started in a well-controlled diabetic patient with microalbuminuria and normal GFR?
What is the expected trend in Glomerular Filtration Rate (GFR) in a patient with Impaired renal function, currently taking Dapagliflozin (Forxiga) 5mg, who has experienced a decline in GFR from 30 ml/min to 25 ml/min?
A 63-year-old woman with advanced chronic kidney disease (estimated glomerular filtration rate ≈16 mL/min/1.73 m²) is taking pioglitazone (Actos) 15 mg daily and dapagliflozin (Farxiga) 10 mg daily; what is the recommended management of her antidiabetic therapy?
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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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