What amount of sodium is excreted with canagliflozin (SGLT2 inhibitor) use?

From the Guidelines

Canagliflozin, an SGLT2 inhibitor, increases sodium excretion by approximately 20-25 mEq per day (or about 460-575 mg of sodium). This sodium excretion occurs primarily during the initial days to weeks of treatment and then tends to return toward baseline with continued therapy. The mechanism involves inhibition of sodium-glucose cotransporters in the proximal tubule of the kidney, which normally reabsorb both glucose and sodium. By blocking these transporters, canagliflozin prevents the reabsorption of both substances, leading to increased urinary excretion of sodium along with glucose. This natriuretic effect contributes to the blood pressure-lowering benefits of SGLT2 inhibitors and may partially explain their cardiovascular and renal protective effects. However, this sodium excretion can potentially lead to volume depletion, especially in patients taking diuretics or those with renal impairment, so monitoring for symptoms of dehydration and hypotension is important when initiating therapy 1.

Key Considerations

• The amount of sodium excreted is approximately 20-25 mEq per day, which is equivalent to about 460-575 mg of sodium.
• This effect is most pronounced during the initial days to weeks of treatment and tends to return toward baseline with continued therapy.
• The mechanism of action involves inhibition of sodium-glucose cotransporters in the proximal tubule of the kidney.
• Monitoring for symptoms of dehydration and hypotension is crucial when initiating therapy, especially in patients with renal impairment or those taking diuretics.

Clinical Implications

• The natriuretic effect of canagliflozin contributes to its blood pressure-lowering benefits and may partially explain its cardiovascular and renal protective effects.
• Patients with type 2 diabetes and chronic kidney disease may benefit from the use of SGLT2 inhibitors, such as canagliflozin, to reduce the risk of cardiovascular events and kidney disease progression 1.
• However, careful consideration of the potential risks and benefits is necessary, particularly in patients with renal impairment or those taking diuretics.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Sodium Excretion with Canagliflozin Use

• The amount of sodium excreted with canagliflozin (SGLT2 inhibitor) use is not directly quantified in the provided studies 2, 3, 4, 5, 6.
• However, it is mentioned that SGLT2 inhibitors, including canagliflozin, increase urinary glucose excretion by suppressing glucose reabsorption at the proximal tubule in the kidney, and this process also involves the excretion of sodium 3, 5, 6.
• The studies suggest that the pharmacodynamic response to SGLT2 inhibitors, including canagliflozin, declines with increasing severity of renal impairment, which may affect the amount of sodium excreted 2, 4, 6.
• One study mentions that SGLT2 inhibitors reduce sodium and glucose reabsorption in the proximal tubule, leading to increased urinary glucose and sodium excretion in patients with type 2 diabetes 5.
• Another study notes that the amount of glucose excreted in the urine depends on both the level of hyperglycemia and the glomerular filtration rate, which may also apply to sodium excretion 6.

Key Findings

• Canagliflozin, as an SGLT2 inhibitor, increases urinary glucose excretion, which is associated with sodium excretion 3, 5, 6.
• The amount of sodium excreted may depend on the level of hyperglycemia and the glomerular filtration rate 6.
• The pharmacodynamic response to canagliflozin declines with increasing severity of renal impairment, which may affect sodium excretion 2, 4, 6.