Efficacy and safety of canagliflozin in subjects with type 2 diabetes: systematic review and meta-analysis

Abstract

Canagliflozin led to improvements in reducing glycated hemoglobin A1c levels and body weight with low risk of hypoglycemia in patients with T2DM. Common adverse effects including genital tract infections and osmotic diuresis-related AEs were identified and reviewed. Risks of cardiovascular events are even less certain, and more data on long-term effects are needed.

Canagliflozin: A Review in Type 2 Diabetes

“…increased urine volume/frequency) occurred in 6.1-fold more canagliflozin (100 or 300 mg/day) than placebo recipients (4.9 and 4.9 vs. 0.8%) in the pooled analysis of four 26-week trials (n = 2313) [40]; these AEs typically occurred during the first 6 weeks of therapy and none were serious [72]. Consistent with these findings, over 12-52 weeks, canagliflozin significantly (p < 0.01) increased the risk of osmotic diuresis-related AEs compared with placebo, as well as active comparators (sitagliptin or glimepiride), in meta-analyses (n = 3853 and 5057) [74].…”

“…UTIs with canagliflozin (100 or 300 mg/day), although often symptomatic, were rarely serious (≤0.2% of patients) [76] and responded to standard therapy without canagliflozin discontinuation [7] when four placebo-controlled studies were pooled. Compared with other active agents, the UTI incidence with canagliflozin did not significantly differ from that with sitagliptin or glimepiride in the meta-analysis of four 12-to 52-week trials [74], with data from individual sitagliptin-or glimepiride-controlled studies of up to 104 weeks' duration generally supporting these findings [15,[34][35][36].…”

“…The likelihood of GMIs with canagliflozin 300 mg/day was significantly greater (4.95-fold; p < 0.00001) than with sitagliptin or glimepiride over 12-52 weeks in a meta-analysis of four active comparator-controlled trials (n = 2510) [74]. Similarly, in individual studies, the GMI incidence was numerically greater with canagliflozin (100 or 300 mg/day) than with sitagliptin or glimepiride regimens over 52 weeks both in men (2-9 vs. 0.5-1%) and women (10-15 vs. 2-4%) [15,34,35], although did not further increase versus glimepiride over 104 weeks [36].…”

“…2), which may contribute to GMIs [7]. Canagliflozin 300 mg/day significantly (p < 0.00001; 3.76-fold) increased the risk of GMIs versus placebo over 12-26 weeks in a meta-analysis of eight placebocontrolled trials (n = 1338) [74]. The most common GMIs with canagliflozin (100 or 300 mg/day) over 26 weeks…”

“…Despite being a common AE with canagliflozin, UTIs did not significantly differ in incidence between canagliflozin 300 mg/day and placebo over 12-26 weeks in the meta-analysis of eight trials [74]. UTIs with canagliflozin (100 or 300 mg/day), although often symptomatic, were rarely serious (≤0.2% of patients) [76] and responded to standard therapy without canagliflozin discontinuation [7] when four placebo-controlled studies were pooled.…”