Effect of canagliflozin on serum electrolytes in patients with type 2 diabetes in relation to estimated glomerular filtration rate (eGFR)
Creators: name: Weir, Matthew R.
name: Kline, Irina
name: Xie, John
name: Edwards, Robert
name: Usiskin, Keith
Publisher: name: Taylor & Francis
Year: 2020
Subjects: subject: Biochemistry
subject: Medicine
subject: Physiology
subject: FOS: Biological sciences
subject: FOS: Biological sciences
subject: Ecology
subject: 69999 Biological Sciences not elsewhere classified
subject: Science Policy
subject: Computational Biology

description: Effects of canagliflozin, a sodium glucose co-transporter 2 inhibitor, on serum electrolytes were evaluated using pooled data from studies of patients with type 2 diabetes mellitus (T2DM). Analyses were performed using two datasets, each including four placebo-controlled studies: Population 1 (<i>N</i> = 2215), patients with baseline estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m<sup>2</sup> (mean = 89.6 mL/min/1.73 m<sup>2</sup>) and Population 2 (<i>N</i> = 721), patients with baseline eGFR ≥45 and &lt;60 mL/min/1.73 m<sup>2</sup> (mean = 53.3 mL/min/1.73 m<sup>2</sup>). ClinicalTrials.gov identifier: NCT01081834. ClinicalTrials.gov identifier: NCT01106625. ClinicalTrials.gov identifier: NCT01106677. ClinicalTrials.gov identifier: NCT01106690. ClinicalTrials.gov identifier: NCT01032629. ClinicalTrials.gov identifier: NCT01064414. ClinicalTrials.gov identifier: NCT01106651. Mean percent changes from baseline in serum electrolytes (potassium, sodium, magnesium, bicarbonate, phosphate, calcium) and outlier analyses were assessed in patients receiving canagliflozin 100 and 300 mg or placebo. Potassium changes were further evaluated based on baseline therapy with anti-hypertensive agents that interfere with potassium excretion (renin-angiotensin aldosterone system-acting agents and/or potassium-sparing diuretics). Mean percent changes from baseline in potassium with canagliflozin 100 and 300 mg and placebo were 0.6%, 1.0%, and 0.5%, respectively (Week 26; Population 1); and 1.7%, 2.8%, and 0.7%, respectively (Week 18/26; Population 2). The proportion of patients who had potassium elevations meeting pre-defined outlier criteria (&gt;5.4 mmol/L [5.4 mEq/L] and &gt;15% increase from baseline) with canagliflozin 100 and 300 mg and placebo was 4.5%, 6.8%, and 4.7% (Population 1); and 5.2%, 9.1%, and 5.5% (Population 2). In both populations, potassium elevations were usually &lt;6.5 mmol/L for patients treated with canagliflozin or placebo; elevations ≥6.5 mmol/L were rare but more frequent in patients taking anti-hypertensive agents that affect potassium excretion in both the canagliflozin and placebo groups. Small mean percent changes in sodium, bicarbonate, and calcium were seen across groups in both populations; small mean percent increases in magnesium and phosphate were seen with canagliflozin vs placebo, but without an increase in patients meeting outlier criteria. Adverse events related to changes in electrolytes were low across groups. 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.