What is the effect of Liraglutide (Glucagon-like peptide-1 receptor agonist) on Acute Kidney Injury (AKI)?

From the Guidelines

Liraglutide should be used with caution in patients with acute kidney injury (AKI) due to the potential risk of worsening kidney function, and its use is not recommended in patients with severe kidney impairment (eGFR <30 mL/min/1.73m²) or end-stage renal disease. When considering the use of liraglutide in patients with kidney disease, it is essential to weigh the potential benefits against the risks. The medication has been shown to have cardiovascular benefits, including reducing the risk of major adverse cardiovascular events (MACE) in patients with type 2 diabetes, as demonstrated in the LEADER trial 1. However, the use of liraglutide in patients with kidney disease requires careful consideration due to the potential risk of acute kidney injury, particularly when combined with other medications that affect kidney function such as diuretics, ACE inhibitors, or NSAIDs 1. Some key points to consider when using liraglutide in patients with kidney disease include:

• Monitoring kidney function regularly, particularly in patients with pre-existing kidney disease or risk factors for AKI
• Avoiding the use of liraglutide in patients with severe kidney impairment (eGFR <30 mL/min/1.73m²) or end-stage renal disease due to limited clinical experience in this population
• Temporarily discontinuing liraglutide if a patient develops AKI until kidney function stabilizes
• Being aware of the potential for gastrointestinal side effects, such as nausea, vomiting, and diarrhea, which may lead to dehydration and worsen kidney function
• Considering alternative treatment options for patients with kidney disease, such as sodium-glucose co-transporter-2 inhibitors (SGLT2i) or metformin, which may have a more favorable safety profile in this population 1.

From the FDA Drug Label

1. 5 Acute Kidney Injury Liraglutide injection has not been found to be directly nephrotoxic in animal studies or clinical trials. There have been postmarketing reports of acute renal failure and worsening of chronic renal failure, which may sometimes require hemodialysis in liraglutide injection-treated patients Use caution when initiating or escalating doses of liraglutide injection in patients with renal impairment

• Liraglutide and Acute Kidney Injury (AKI): Liraglutide has not been found to be directly nephrotoxic, but there have been postmarketing reports of acute renal failure and worsening of chronic renal failure.
• Key Considerations:
  • Use caution when initiating or escalating doses of liraglutide in patients with renal impairment.
  • Monitor patients for signs and symptoms of AKI, especially those with pre-existing renal disease.
  • Discontinue liraglutide if AKI occurs, and consider alternative treatments. 2

From the Research

Liraglutide and Acute Kidney Injury

• Liraglutide, a glucagon-like peptide-1 receptor agonist, has been associated with acute kidney injury (AKI) in a case report published in 2012 3.
• The case report described a 53-year-old woman who developed severe gastrointestinal symptoms, dehydration, and AKI after starting liraglutide for uncontrolled type 2 diabetes.
• The patient's renal biopsy showed acute tubular necrosis, and the use of the Naranjo adverse drug reaction probability scale indicated a possible relationship between liraglutide and AKI.

Management of Acute Kidney Injury

• The management of patients at risk of AKI involves awareness campaigns, education for healthcare professionals, and electronic early warning systems to improve outcomes 4.
• Fluid management should aim for early, rapid restoration of circulatory volume, but should be more limited after the first 24-48 hours to avoid volume overload.
• Renal replacement therapy should only be started on the basis of hard criteria, but should not be delayed when criteria are met.

Association between Metformin and Acute Kidney Injury

• Metformin use has been associated with reduced risk-adjusted mortality in patients with AKI and type 2 diabetes in a retrospective cohort study published in 2021 5.
• However, another study published in 2021 found that metformin was associated with an increased odds ratio for AKI in patients with type 2 diabetes hospitalized with acute infection, although this association was not independent of other antidiabetics 6.

Acute Kidney Injury and Hypoglycemia

• AKI has been identified as a strong risk factor for hypoglycemia in hospitalized patients with type 2 diabetes, with a higher risk of hypoglycemia associated with longer duration of AKI 7.
• The severity of AKI was also associated with mortality, but showed no significant association with hypoglycemia.