GSK1292263 - GSK
Novel effects on lipids of GSK1292263, a GPR119 agonist, in type 2 diabetics (ADA 2012) - May 25, 2012 - Presentation time: 6/9/2012 11:30:00 AM; P2,N=66; Article describes the safety, tolerability and PK of GSK1292263 and reported that 100-600mg/day for 14 days (n≈12 per arm) did not reduce AUCglucose (0-24h) as monotherapy or dosed with metformin or sitagliptin, but it increased circulating gut hormone levels, especially postprandial PYY; GSK1292263 also reduced significantly apoB(B100), with trends for a reduction of apoE and an elevation of apoA1 
P2 data • Diabetes
http://www.abstractsonline.com/Plan/ViewAbstract.aspx?mID=2936&cKey=1c86104a-9a6a-4c85-b230-4601979649da&sKey=07aff962-bab8-4955-800c-f731d933d91d
 
American Diabetes Association - 72nd Scientific Sessions June 8 - 12, 2012, Philadelphia, PA
 
May 25, 2012
 
Abstract # 1084-P Abstract:     GPR119 receptor agonists improve glucose control in animal models of type 2 diabetes (T2D). GSK1292263, a selective and potent GPR119 agonist, was investigated in two randomized, placebo-controlled studies with T2D patients either washed off prior anti-diabetic medications (NCT01119846) or on metformin monotherapy (NCT01128621). Previously, we described the safety, tolerability and PK of GSK1292263 and reported that 100-600mg/day for 14 days (n≈12 per arm) did not reduce AUCglucose (0-24h) as monotherapy or dosed with metformin or sitagliptin, but it increased circulating gut hormone levels, especially postprandial PYY. We now present novel plasma lipid effects of GSK1292263 observed in these studies with the highest doses, 300mg BID and 600mg QD.                  For GSK1292263 monotherapy Parameter (* = fasting) % Change from Baseline: Comparison to Placebo Least Squares Mean Lower 95% CI Upper 95% CI HDL-C* 300mg BID +26.9 +15.8 +37.9 HDL-C* 600mg QD +20.6 +9.6 +31.6 LDL-C* 300mg BID -23.5 -40.1 -6.9 LDL-C* 600mg QD -22.4 -39.0 -5.8 Triglycerides* 300mg BID -24.7 -47.6 -1.9 Triglycerides* 600mg QD -32.5 -55.4 -9.6 Triglycerides AUC(0-24h) 300mg BID -68.5 -129.5 -7.6 Triglycerides AUC(0-24h) 600mg QD -73.3 -135.7 -10.8 For GSK1292263 co-dosed with metformin: Parameter (* = fasting) % Change from Baseline: Comparison to Placebo Least Squares Mean Lower 95% CI Upper 95% CI HDL-C* 300mg BID +29.0 +18.6 +39.5 HDL-C* 600mg QD +10.5 +0.5 +20.5 LDL-C* 300mg BID -35.5 -49.0 -22.0 LDL-C* 600mg QD -25.2 -38.2 -12.3 Triglycerides* 300mg BID -63.0 -88.5 -37.5 Triglycerides* 600mg QD -53.2 -77.8 -28.7 Triglycerides AUC(0-24h) 300mg BID -82.1 -124.2 -40.0 Triglycerides AUC(0-24h) 600mg QD -72.0 -114.1 -29.9 In both studies, GSK1292263 also reduced significantly apoB(B100), with trends for a reduction of apoE and an elevation of apoA1. Sitagliptin 100mg had no significant lipid effects.These data suggest that GPR119 agonism with GSK1292263 can provide clinically meaningful lipid improvements in T2D patients.