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| |  Combination Sitagliptin and Metformin Shows Substantial Beta-Cell Function Improvement at 2 Years: Presented at ADA By Bruce Sylvester SAN FRANCISCO -- June 9, 2008 -- Type 2 diabetic patients using combination sitagliptin and metformin have achieved substantial sustained improvements in beta-cell function after 2 years, correlating with decreases in haemoglobin (Hb) A1C levels, researchers reported here at the American Diabetes Association (ADA) 68th Scientific Sessions. "In this study, we saw both sustained beta-cell improved function over time and sustained improvements in Hb A1C," said Deborah Williams-Herman, MD, Merck Research Laboratories, Rahway, New Jersey, at her poster presentation here on June 8. "The combination of sitagliptin and metformin was well tolerated over time," she added. In the initial 24-week phase of the study, the investigators treated 1,091 patients with the sitagliptin/metformin combination or placebo; this was followed by an active-treatment phase, in which the 762 placebo subjects were switched to metformin. Five hundred eighty-seven subjects continued in the extension trial for 104 weeks, and 402 of these individuals were included in the all-patients analysis. Five treatment regimens for these 402 subjects comprised the following: (1) sitagliptin 50 mg BID plus metformin 500 mg BID (n = 96); (2) sitagliptin 50 mg BID plus metformin 1,000 mg BID (n = 105); (3) metformin 1,000 mg BID (n = 87); (4) metformin 500 mg BID (n = 67); or (5) sitagliptin 100 mg daily (n = 50). To assess beta-cell function at 104 weeks, the investigators analysed data on 125 self-selected subjects who underwent a frequently sampled meal-tolerance test at baseline and again at week 104. These subjects ate a standard meal (1 nutrition bar and 1 nutrition drink within 15 minutes) followed by blood collection at different time points relative to initiating the meal. At 104 weeks, the researchers reported substantial improvements in the steady-state rate of insulin secretion expressed as a function of glucose concentration. The median increases in these improvements from baseline to 2 years were as follows: groups (1) 20.2; (2) 22.5; (3) 10.4; (4) 9.8; and (5) 13.6. Also at 104 weeks, the mean Hb A1C reductions from baseline were as follows: groups (1) 1.4%; (2) 1.7%; (3) 1.3%; (4) 1.1%; and (5) 1.2%. "When you translate these data, they show increased responsivity of the beta cell to glucose among treated patients," concluded Dr. Williams-Herman. "You see that [measurement] translated into Hb A1C lowering over time, since they go hand-in-hand." Sitagliptin is a dipeptidyl peptidase-4 inhibitor, which inhibits the degradation of intact (active) incretins, resulting in 2- to 3-fold increases in active incretin (GLP-1) levels. In healthy subjects, metformin augments total GLP-1 levels, and sitagliptin and metformin, when coadministered, have at least additive effects on active GLP-1. Funding for this study was provided by Merck & Co., Inc.
[Presentation title: Substantial Improvement in Beta-Cell Function With Initial Combination Therapy of Sitagliptin and Metformin in Patients With Type 2 Diabetes After 1 Year of Treatment. Abstract 543-P]
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