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

Abstract

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).

Research design and 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 m² (mean = 89.6 mL/min/1.73 m²) and Population 2 (N = 721), patients with baseline eGFR ≥45 and <60 mL/min/1.73 m² (mean = 53.3 mL/min/1.73 m²).

Clinical trial registration:

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.

Main outcome measures:

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.

Keywords::

• Canagliflozin
• Sodium glucose co-transporter 2 (SGLT2) inhibitor
• Type 2 diabetes mellitus
• Electrolytes
• Potassium
• Phosphate
• Calcium

Transparency

Declaration of funding

Canagliflozin has been developed by Janssen Research & Development, LLC, in collaboration with Mitsubishi Tanabe Pharma Corporation. Janssen Research & Development, LLC, was involved in study design and conduct, and acquisition, analysis, and interpretation of the data. The manuscript was prepared by the authors, with editorial assistance funded by the sponsor. All authors had full access to the data, were responsible for the integrity of the data and the accuracy of the data analysis, and reviewed, edited, and approved the manuscript for publication.

Declaration of financial/other relationships

M.R.W. is a scientific consultant for Janssen. I.K., J.X., R.E., and K.U. are current or former employees of Janssen Research & Development, LLC. CMRO Peer Reviewers on this manuscript have received an honorarium from CMRO for their review work, but have no relevant financial or other relationships to disclose.

Acknowledgments

The authors thank all investigators, study teams, and patients for participating in this study. Editorial support was provided by Katie McClendon, PhD, of MedErgy, and was funded by Janssen Scientific Affairs, LLC.