Canagliflozin, a sodium glucose co-transporter 2 inhibitor, reduces post-meal glucose excursion in patients with type 2 diabetes by a non-renal mechanism: results of a randomized trial
| Autor: | Eunice Artis, Linda Morrow, David Polidori, Sarah Rusch, Nicole Vaccaro, Jolene K. Berg, Peter P. Stein, Damayanthi Devineni |
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| Rok vydání: | 2014 |
| Předmět: |
Blood Glucose
Male medicine.medical_specialty medicine.drug_class Endocrinology Diabetes and Metabolism Thiophenes Type 2 diabetes Kidney Placebo Excretion Endocrinology Double-Blind Method Glucosides Sodium-Glucose Transporter 2 Internal medicine medicine Humans Canagliflozin Sodium-Glucose Transporter 2 Inhibitors Cross-Over Studies business.industry Fasting Middle Aged Postprandial Period medicine.disease Sulfonylurea Crossover study Metformin Glucose Postprandial Diabetes Mellitus Type 2 Female business medicine.drug |
| Zdroj: | Metabolism. 63:1296-1303 |
| ISSN: | 0026-0495 |
| Popis: | Objective Canagliflozin is a sodium glucose co-transporter 2 inhibitor approved for treating patients with type 2 diabetes. This study evaluated renal and non-renal effects of canagliflozin on postprandial plasma glucose (PG) excursion in patients with type 2 diabetes inadequately controlled with metformin. Materials/Methods Patients (N=37) were randomized to a four-period crossover study with 3-day inpatient stays in each period and 2-week wash-outs between periods. Patients received Treatments (A) placebo/placebo, (B) canagliflozin 300mg/placebo, (C) canagliflozin 300mg/canagliflozin 300mg, or (D) canagliflozin 300mg/canagliflozin 150mg on Day 2/Day 3 in one of four treatment sequences (similar urinary glucose excretion [UGE] expected for Treatments B–D). A mixed-meal tolerance test (MMTT) was given 20minutes post-dose on Day 3 of each period. Results A single dose of canagliflozin 300mg reduced both fasting and postprandial PG compared with placebo, with generally similar effects on fasting PG and UGE observed for Treatments B–D. An additional dose of canagliflozin 300mg (Treatment C), but not 150mg (Treatment D), prior to the MMTT on Day 3 provided greater postprandial PG reduction versus placebo (difference in incremental glucose AUC 0–2h , −7.5% for B vs A; −18.5% for C vs A; −12.0% [ P =0.012] for C vs B), leading to modestly greater reductions in total glucose AUC 0–2h with Treatment C versus Treatment B or D. Canagliflozin was generally well tolerated. Conclusions These findings suggest that a non-renal mechanism (ie, beyond UGE) contributes to glucose lowering for canagliflozin 300mg, but not 150mg. |
| Databáze: | OpenAIRE |
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