Canagliflozin as monotherapy and as combination therapy was generally well tolerated in patients with T2DM inadequately controlled on their current diabetes mellitus treatment.

clinicaltrials.gov Identifier: NCT01915498.

The effects of canagliflozin, a sodium glucose co-transporter 2 inhibitor, on blood pressure (BP) and osmotic diuresis-and intravascular volume reduction-related adverse events (AEs) were evaluated using pooled data from four placebo-controlled, phase 3 studies in patients with type 2 diabetes mellitus (T2DM; N=2313). At baseline, 1332 (57.6%) patients were taking an antihypertensive medication. Canagliflozin 100 mg and 300 mg provided reductions (95% confidence interval [CI] .1], respectively). In patients with elevated SBP at baseline, placebo-subtracted reductions (95% CI) in SBP with canagliflozin 100 mg and 300 mg were À6.0 mm Hg (À9.1 to À2.9) and À7.4 mm Hg (À10.4 to À4.4), respectively. Placebo-subtracted changes in DBP were 1.5 mm Hg (À1.6 to 4.5) and À1.6 mm Hg (À4.5 to 1.2), respectively, in those with elevated DBP at baseline. Canagliflozin 100 mg and 300 mg were associated with increased incidence of osmotic diuresis-related AEs (eg, pollakiuria [increased urine volume] and polyuria [increased urine frequency]) vs placebo (6.7%, 5.6%, and 0.8%). The incidence of intravascular volume reduction-related AEs (eg, orthostatic hypotension and postural dizziness) was low across groups (1.2%, 1.3%, and 1.1%). In summary, canagliflozin was associated with reduced BP in patients with T2DM across a range of baseline BPs, with increased incidence of AEs related to osmotic diuresis but not intravascular volume reduction. J Clin Hypertens (Greenwich). 2014;16:875-882. ª

Background/Aims: Some sodium glucose co-transporter 2 (SGLT2) inhibitors are approved for the treatment of patients with type 2 diabetes mellitus (T2DM) with an estimated glomerular filtration rate (eGFR) of ≥45 ml/min/1.73 m². The efficacy and safety of canagliflozin, an approved SGLT2 inhibitor, was evaluated in patients with stage 3 chronic kidney disease (CKD; eGFR ≥30 to <60 ml/min/1.73 m²). Methods: This analysis used integrated data from four randomized, placebo-controlled, phase 3 studies that enrolled patients with T2DM and stage 3 CKD. Results are presented for the overall population as well as subgroups with stage 3a CKD (eGFR ≥45 and <60 ml/min/1.73 m²) and stage 3b CKD (eGFR ≥30 and <45 ml/min/1.73 m²). Results: Among all subjects studied with stage 3 CKD, placebo-subtracted reductions in HbA_1c (-0.38 and -0.47%; p < 0.001), body weight (-1.6 and -1.9%; p < 0.001), and systolic blood pressure (-2.8 and -4.4 mm Hg; p < 0.01) were seen with canagliflozin 100 and 300 mg, respectively. Decreases in HbA_1c, body weight, and systolic blood pressure were examined in the stage 3a and 3b CKD subgroups, with greater decreases in HbA_1c, -0.47% (-0.61, -0.32) and body weight in subjects in stage 3a CKD, -1.8% (-2.3, -1.2) with canagliflozin 100 mg. Initial declines in eGFR were seen early following treatment initiation with canagliflozin, but trended towards baseline over time. The most common adverse events with canagliflozin included genital mycotic infections and adverse events related to reduced intravascular volume likely secondary to osmotic diuresis. Conclusion: In subjectswith T2DM and stage 3 CKD, canagliflozin reduced HbA_1c, body weight, and blood pressure, and was generally well tolerated.

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.