Comparative Pharmacology
Head-to-head clinical analysis: INVOKAMET versus INVOKAMET XR.
Peer-Reviewed Evidence
Head-to-head clinical analysis: INVOKAMET versus INVOKAMET XR.
INVOKAMET vs INVOKAMET XR
Comparing the clinical profiles, pharmacokinetic behaviors, and safety indices of these two therapeutic agents.
INVOKAMET is a combination of canagliflozin, an SGLT2 inhibitor, and metformin, a biguanide. Canagliflozin inhibits sodium-glucose cotransporter 2 in the renal proximal tubules, reducing glucose reabsorption and increasing urinary glucose excretion. Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity.
Combination of canagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, which reduces renal glucose reabsorption and lowers blood glucose, and metformin, an activator of AMP-activated protein kinase (AMPK) that decreases hepatic glucose production and improves insulin sensitivity.
Oral: Starting dose: 5 mg canagliflozin/500 mg metformin hydrochloride extended-release twice daily; titrate based on efficacy and tolerability, maximum 150 mg/1000 mg twice daily.
Maximum daily dose: canagliflozin 300 mg/metformin ER 2000 mg orally once daily with the morning meal. Initial dose: canagliflozin 50 mg/metformin ER 500 mg orally twice daily or canagliflozin 150 mg/metformin ER 1000 mg orally once daily; for patients not currently on metformin, start with canagliflozin 50 mg/metformin ER 500 mg orally twice daily; for patients on metformin, switch to INVOKAMET XR based on current metformin dose.
None Documented
None Documented
Canagliflozin: 10–13 hours (multiple dosing); Metformin: 6.2 hours (plasma). Accumulation occurs in renal impairment.
Canagliflozin: mean terminal elimination half-life is 13.1 hours (range 11-16 hours) for the 300 mg dose, consistent with once-daily dosing. Metformin: terminal elimination half-life is approximately 6.2 hours (range 4-9 hours) in patients with normal renal function; prolonged in renal impairment.
Canagliflozin (SGLT2 inhibitor): ~33% renal (1% unchanged, ~33% as glucuronide metabolites), ~52% fecal. Metformin (biguanide): 90% renal unchanged via tubular secretion.
Canagliflozin is primarily excreted as unchanged drug in urine (approximately 33%) and feces (approximately 41%), with about 7% as metabolites in urine and 34% as metabolites in feces. Metformin is excreted unchanged in urine (90-100% of absorbed dose) via tubular secretion and glomerular filtration.
Category C
Category C
SGLT2 Inhibitor / Biguanide Combination
SGLT2 Inhibitor / Biguanide Combination