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


METHODS
Analyses were performed using two datasets, each including four placebo-controlled studies: Population 1 (N = 2215), patients with baseline estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m(2) (mean = 89.6 mL/min/1.73 m(2)) and Population 2 (N = 721), patients with baseline eGFR ≥45 and <60 mL/min/1.73 m(2) (mean = 53.3 mL/min/1.73 m(2)).


BACKGROUND
ClinicalTrials.gov, NCT01081834; NCT01106625; NCT01106677; NCT01106690; NCT01032629; NCT01064414; NCT01106651.


METHODS
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).


RESULTS
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 (>5.4 mmol/L [5.4 mEq/L] and >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 <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.


CONCLUSIONS
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.
Division of Nephrology, University of Maryland School of Medicine , Baltimore, MD , USA.
Matthew R
MR
Weir
Irina
I
Kline
John
J
Xie
Robert
R
Edwards
Keith
K
Usiskin
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D000068896:Canagliflozin; D017326:Clinical Trials, Phase III as Topic; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004573:Electrolytes / Q000097:blood*; D005260:Female; D005919:Glomerular Filtration Rate; D005960:Glucosides / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D013876:Thiophenes / Q000009:adverse effects* / Q000627:therapeutic use; D014883:Water-Electrolyte Imbalance / Q000097:blood / Q000139:chemically induced* / Q000175:diagnosis
D015415:Biomarkers; D004573:Electrolytes; D005960:Glucosides; D007004:Hypoglycemic Agents; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D013876:Thiophenes; D000068896:Canagliflozin
Calcium; Canagliflozin; Electrolytes; Phosphate; Potassium; Sodium glucose co-transporter 2 (SGLT2) inhibitor; Type 2 diabetes mellitus