Core evidence clinical impact summary for canagliflozin
| Outcome measure | Evidence | Implications |
|---|---|---|
| Disease-oriented evidence | ||
| Glycemic efficacy versus placebo | Clear (pair-wise meta-analyses of randomized controlled trials [RCTs]) | Canagliflozin 100 and 300 mg once daily reduce HbA1c by 0.6%–0.8%, respectively |
| Glycemic efficacy versus other antidiabetic agents | Clear versus sitagliptin (pair-wise meta-analyses of RCTs) Substantial versus other comparators (network meta-analyses of RCTs) | Canagliflozin 300 mg reduces HbA1c by 0.2% compared with sitagliptin 100 mg Canagliflozin may be slightly more effective in reducing HbA1c compared with other SGLT2 inhibitors, linagliptin, and saxagliptin, and appears to be of similar efficacy with sulfonylureas, pioglitazone, and glucagon-like peptide-1 receptor agonists (GLP-1 RA) |
| Reduction in body weight | Clear versus placebo and sitagliptin (pair-wise meta-analyses of RCTs) Substantial versus other comparators (network meta-analyses of RCTs) | Canagliflozin 100 and 300 mg confer reductions of 2 and 2.8 kg in body weight compared with placebo, respectively Canagliflozin seems to be more effective in reducing body weight compared with DPP-4 inhibitors |
| Reduction in arterial blood pressure | Clear versus placebo and sitagliptin (pair-wise meta-analyses of RCTs) Substantial versus other comparators (network meta-analyses of RCTs) | Compared with placebo, canagliflozin 100 and 300 mg reduce systolic blood pressure by 4.2 and 5.4 mmHg, respectively Canagliflozin reduces systolic blood pressure by 4 mmHg compared with sitagliptin Canagliflozin is superior to sulfonylureas and saxagliptin, and similar to pioglitazone, linagliptin, vildagliptin, and GLP-1 RA in terms of systolic blood pressure reduction |
| Patient-oriented evidence | ||
| Hypoglycemia | Clear versus placebo and sitagliptin (pair-wise meta-analyses of RCTs) Substantial versus other comparators (network meta-analyses of RCTs) | Canagliflozin is associated with an increased risk for hypoglycemia compared with placebo (odds ratio ranging between 1.5 and 1.6) and is similar to sitagliptin Risk for hypoglycemia with canagliflozin seems to be lower compared with sulfonylureas, and similar to other DPP-4 inhibitors and GLP-1 RA |
| Urinary and genital tract infections | Clear (pair-wise and network meta-analyses of RCTs) | Incidence of urinary tract infections does not significantly differ between canagliflozin and placebo Incidence of genital infections is higher with canagliflozin compared with placebo (odds ratio ranging between 4.9 and 5.2) and compared with active control (excluding other SGLT2 inhibitors) |
| Intravascular volume reduction and osmotic diuresis Cardiovascular outcomes | Substantial (pooled analyses of RCTs) Moderate (meta-analyses of short-term RCTs) | Canagliflozin is associated with an increased incidence of adverse events related to osmotic diuresis compared with placebo Canagliflozin is not associated with increased risk for all-cause mortality and cardiovascular outcomes |
| Economic evidence | ||
| Monotherapy | Substantial (mostly conference abstracts of cost-effectiveness studies) | In the UK, canagliflozin as monotherapy appears to be cost-effective versus DPP-4 inhibitors, but not versus sulfonylureas or pioglitazone |
| Dual therapy | Substantial (mostly conference abstracts of cost-effectiveness studies) | As add-on to metformin, canagliflozin is likely to be cost-effective compared to sitagliptin in the UK, Ireland, France, Belgium, Sweden, Norway, Spain, Portugal, Slovakia, and the Czech Republic In comparison to sulfonylureas, canagliflozin seems cost-effective in Ireland, Belgium, Sweden, Norway, Poland, and the Czech Republic |
| Triple therapy | Substantial (mostly conference abstracts of cost-effectiveness studies) | As add-on to metformin and sulfonylurea, canagliflozin is likely to be cost-effective compared with sitagliptin in the UK, Ireland, France, Belgium, Norway, Spain, Portugal, Slovakia, the Czech Republic, Canada, and Brazil |