Comparative Pharmacology
Head-to-head clinical analysis: AVANDAMET versus INVOKAMET XR.
Peer-Reviewed Evidence
Head-to-head clinical analysis: AVANDAMET versus INVOKAMET XR.
AVANDAMET vs INVOKAMET XR
Comparing the clinical profiles, pharmacokinetic behaviors, and safety indices of these two therapeutic agents.
AVANDAMET combines rosiglitazone, a thiazolidinedione that improves insulin sensitivity by activating peroxisome proliferator-activated receptor gamma (PPARγ), and metformin, a biguanide that decreases hepatic glucose production, reduces intestinal glucose absorption, 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, initial dose of rosiglitazone 4 mg/metformin 500 mg twice daily or rosiglitazone 2 mg/metformin 500 mg twice daily; maximum recommended dose rosiglitazone 8 mg/metformin 2000 mg per day.
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
Rosiglitazone: 3-4 hours (terminal); metformin: 6.2 hours (terminal). No accumulation with normal renal function.
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.
Renal (90-95% as unchanged drug for rosiglitazone; metformin is 90% renally eliminated unchanged). Biliary/fecal: minor (<5% for both).
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
Thiazolidinedione and Biguanide Combination
SGLT2 Inhibitor / Biguanide Combination