Effect of canagliflozin on serum electrolytes in patients with type 2 diabetes in relation to estimated glomerular filtration rate (eGFR)

Abstract

In patients with T2DM, canagliflozin was generally associated with small mean percent changes in serum electrolytes. Infrequent episodes of potassium elevation occurred with canagliflozin 300 mg, but occurred more often in patients with reduced eGFR.

Renal effects of canagliflozin in type 2 diabetes mellitus

“…Small changes in serum electrolyte levels (e.g., potassium, magnesium and phosphate) have been previously reported in patients with T2DM, especially in patients with reduced eGFR and in patients treated with canagliflozin 300 mg 52,53 . In addition, comorbid hypertension is common in patients with T2DM, and treatment with ACE inhibitors, ARBs and/or potassium-sparing diuretics can interfere with potassium excretion, particularly in patients with reduced eGFR 53 .…”

“…The proportions of patients who had potassium levels meeting outlier criteria (4upper limit of normal [ULN; 5.4 mmol/L] and 415% increase from baseline) at any time post-baseline with canagliflozin 100 and 300 mg and placebo were 4.5%, 6.8% and 4.7%, respectively, for those with eGFR !60 mL/min/1.73 m 2 ; for those with eGFR !45 and 560 mL/min/1.73 m 2 , 5.2%, 9.1% and 5.5% met outlier criteria for potassium, respectively 53 . Episodes where potassium elevations were considered to be clinically significant enough to be reported as AEs were less frequent overall.…”

“…In addition, comorbid hypertension is common in patients with T2DM, and treatment with ACE inhibitors, ARBs and/or potassium-sparing diuretics can interfere with potassium excretion, particularly in patients with reduced eGFR 53 . Thus, it is important to understand the potential effects of changes in renal function on the risk of potassium elevations that are associated with canagliflozin treatment.…”

Management of Hyperglycemia in Type 2 Diabetes, 2015: A Patient-Centered Approach: Update to a Position Statement of the American Diabetes Association and the European Association for the Study of Diabetes

“…Reversible small increases in serum creatinine occur (14,19). Increased urine calcium excretion has been observed (20), and the U.S. Food and Drug Administration (FDA) mandated a follow-up of upper limb fractures of patients on canagliflozin after an adverse imbalance in cases was reported in short-term trials (21). Small increases in LDL cholesterol (;5%) have been noted in some trials, the implications of which are unknown.…”

Elevated serum magnesium associated with SGLT2 inhibitor use in type 2 diabetes patients: a meta-analysis of randomised controlled trials

“…SGLT2 inhibitors selectively inhibit renal glucose reabsorption and increase urinary glucose excretion (UGE) [1]. As a consequence of increased UGE, treatment with SGLT2 inhibitors may result in osmotic diuresis, which may trigger volume depletion and dehydration [2]. However, data on the influence of such haemodynamic changes on renal electrolyte handling in individuals with type 2 diabetes is lacking.…”