From the Guidelines
SGLT-2 inhibitors do not cause hyperkalemia and may actually reduce the risk of high potassium levels. These medications work by preventing glucose reabsorption in the kidneys, leading to increased glucose excretion in urine, and have a mild osmotic diuretic effect that can help reduce potassium levels slightly 1. Unlike some other medications used for diabetes or heart failure, such as ACE inhibitors, ARBs, or certain diuretics, SGLT-2 inhibitors typically do not disrupt potassium balance in a way that raises serum potassium levels.
Some of the key benefits of SGLT-2 inhibitors include:
- Reducing the risk of hyperkalemia without causing hypokalemia 1
- Mitigating fluid retention 1
- Facilitating the initiation and persistent use of other guideline-directed medical therapies, such as RAS inhibitors, mineralocorticoid receptor antagonists, and endothelin antagonists 1
- Decreasing the risk of hyperkalemia and slowing the progression of kidney dysfunction, which can improve tolerance of other heart failure therapies 1
It's essential to monitor electrolytes when starting any new medication, especially in patients with reduced kidney function, as individual responses can vary. However, based on the most recent and highest quality evidence, SGLT-2 inhibitors are a safe and potentially beneficial option for patients at risk of hyperkalemia 1.
From the Research
SGLT2 Inhibitors and Hyperkalemia
- The risk of hyperkalemia associated with SGLT2 inhibitors has been evaluated in several studies 2, 3, 4, 5, 6.
- A population-based cohort study found that initiation of SGLT2 inhibitors was associated with a lower risk of hyperkalemia compared with DPP-4 inhibitors (hazard ratio 0.74; 95% confidence interval 0.68-0.80) 2.
- Another study found that SGLT2 inhibitors either cause no effect or a slight reduction in plasma K+ concentration in patients with normal kidney function, but seem to exert a protective effect against hyperkalemia in the setting of reduced kidney function or when given with drugs that block the renin-angiotensin-aldosterone axis 3.
- A pooled analysis of clinical trials found that the SGLT2 inhibitor dapagliflozin was not associated with an increased risk of hyperkalemia or severe hypokalemia in patients with type 2 diabetes mellitus 4.
- A study investigating the risk of hyperkalaemia in patients with type 2 diabetes mellitus prescribed with SGLT2 versus DPP-4 inhibitors found that use of SGLT2 inhibitors was associated with a 29% reduction in incident severe hyperkalaemia (hazard ratio 0.71,95% confidence interval 0.58-0.88) compared with DPP-4 inhibitors 5.
- The diuretic effects of SGLT2 inhibitors have been reviewed, and it has been noted that they present some favourable properties, including preserved potassium balance and lower risk of acute renal injury 6.
Key Findings
- SGLT2 inhibitors are associated with a lower risk of hyperkalemia compared with DPP-4 inhibitors 2, 5.
- SGLT2 inhibitors do not increase the risk of hyperkalemia or severe hypokalemia in patients with type 2 diabetes mellitus 4.
- The diuretic effect of SGLT2 inhibitors may contribute to the improvement of renal outcomes, including reduced albuminuria and dampened risk of heart failure 6.