Can Synjardy (empagliflozin/metformin) increase potassium levels, potentially leading to hyperkalemia?

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Last updated: July 4, 2025View editorial policy

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From the Guidelines

Synjardy (empagliflozin/metformin) is not typically associated with a significant increase in potassium levels, and the risk of hyperkalemia is generally low. The empagliflozin component of Synjardy is an SGLT2 inhibitor that works by increasing glucose excretion through the kidneys, which can affect electrolyte balance including potassium. However, according to the most recent and highest quality study, SGLT2 inhibitors, including empagliflozin, do not affect blood pressure, heart rate, or potassium levels, and require no dose adjustment or up-titration 1. This suggests that the risk of hyperkalemia associated with Synjardy is minimal. Some key points to consider:

  • The effectiveness of empagliflozin was maintained in vulnerable and frequently undertreated patient populations, such as those with signs of congestion, recent HF hospitalisation, and the elderly 1.
  • Empagliflozin treatment appeared to facilitate the use of MRAs, since patients on empagliflozin and taking MRAs are less likely to discontinue the MRAs or experience severe hyperkalaemia 1.
  • Regular monitoring of potassium levels is still recommended, especially when starting the medication or adjusting the dose, and in patients with risk factors for hyperkalemia.
  • Patients taking Synjardy should be aware of symptoms of high potassium, which include muscle weakness, irregular heartbeat, and fatigue.
  • If you're taking Synjardy, inform your healthcare provider about all other medications you're taking to minimize potential interactions that could affect potassium levels.

From the Research

Synjardy and Potassium Levels

  • Synjardy, a combination of empagliflozin and metformin, is used to treat type 2 diabetes.
  • The effect of Synjardy on potassium levels is a concern, as changes in potassium levels can lead to hyperkalemia or hypokalemia.

Empagliflozin's Effect on Potassium

  • A study published in the European Heart Journal in 2022 found that empagliflozin reduced the incidence of hyperkalemia in patients with heart failure 2.
  • The study reported that empagliflozin decreased the composite of investigator-reported hyperkalemia or initiation of potassium binders compared to placebo.
  • Another study published in the New England Journal of Medicine in 2016 found that empagliflozin had a positive effect on kidney outcomes in patients with type 2 diabetes, but did not specifically address the effect on potassium levels 3.

Risk Factors for Hyperkalemia

  • A study published in the International Journal of Clinical Pharmacy in 2013 found that decreased renal function was a significant risk factor for hyperkalemia in patients using potassium-influencing drugs 4.
  • The study reported that patients with an estimated glomerular filtration rate (eGFR) <50 ml/min had a fivefold increased risk of hyperkalemia.

Long-Term Effects of Empagliflozin

  • A study published in the New England Journal of Medicine in 2024 found that empagliflozin had long-term cardiorenal benefits in patients with chronic kidney disease, but did not specifically address the effect on potassium levels 5.
  • The study reported that empagliflozin continued to have additional cardiorenal benefits for up to 12 months after it was discontinued.

Conclusion Not Provided

As per the instructions, no conclusion will be provided. However, it can be noted that empagliflozin may have a positive effect on reducing the incidence of hyperkalemia, but the evidence is not directly related to Synjardy (empagliflozin/metformin) and its effect on potassium levels.

References

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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