Dapagliflozin, a novel, selective SGLT2 inhibitor, improved glycemic control over 2 weeks in patients with type 2 diabetes mellitus.

Abstract

Dapagliflozin, administered to patients in once-daily oral doses, is a sodium-glucose cotransporter 2 (SGLT2) inhibitor that blocks the reabsorption of glucose from urine into the blood. This 14-day study randomized patients with type 2 diabetes mellitus (T2DM) to four treatment groups receiving daily oral doses of 5-, 25-, or 100-mg doses of dapagliflozin or placebo, in order to evaluate glucosuria and glycemic parameters. Significant reductions in fasting serum glucose (FSG) were observed on day 2 with 100 mg dapagliflozin (-9.3%, P < 0.001), and dose-dependent reductions were observed on day 13 with the 5-mg (-11.7%; P < 0.05), 25-mg (-13.3%; P < 0.05), and 100-mg (-21.8%; P < 0.0001) doses as compared with placebo. Significant improvements in oral glucose tolerance test (OGTT) were observed with all doses on days 2 and 13 (P < 0.001 as compared with placebo). On day 14, urine glucose values were 36.6, 70.1, and 69.9 g/day for the 5-, 25-, and 100-mg doses (as compared with no change for placebo), which were slightly lower than those on day 1. This was attributed to the decrease in filtered glucose load following improved glycemic control. Dapagliflozin produced dose-dependent increases in glucosuria and clinically meaningful changes in glycemic parameters in T2DM patients.

• Authors: B Komoroski, N Vachharajani, Y Feng, L Li, D Kornhauser, M Pfister
• Journal: Clinical pharmacology and therapeutics (Clin Pharmacol Ther) Vol. 85 Issue 5 Pg. 513-9 (May 2009) ISSN: 1532-6535 [Electronic] United States
• PMID: 19129749 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Benzhydryl Compounds
• Blood Glucose
• Glucosides
• Hypoglycemic Agents
• SLC5A2 protein, human
• Sodium-Glucose Transporter 2
• Sodium-Glucose Transporter 2 Inhibitors
• dapagliflozin

Topics

• Administration, Oral
• Benzhydryl Compounds
• Blood Glucose (drug effects)
• Diabetes Mellitus, Type 2 (drug therapy, physiopathology)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Female
• Glucose Tolerance Test
• Glucosides (administration & dosage, adverse effects)
• Glycosuria (chemically induced)
• Humans
• Hypoglycemic Agents (administration & dosage, adverse effects)
• Male
• Middle Aged
• Sodium-Glucose Transporter 2
• Sodium-Glucose Transporter 2 Inhibitors
• Time Factors