DS-8500a improves glycaemic, lipid variables in T2D
The novel, G-protein coupled receptor 119 (GPR119) agonist DS-8500a demonstrated dose-dependent glucose-lowering effects and favourable improvements in lipid parameters that extended up to 12 weeks in Japanese patients with type 2 diabetes mellitus (T2D), according to data presented at EASD 2017.
This multicentre, double-blind trial comprised 368 patients with T2D and HbA1c levels between ≥7 and <10 percent. Participants were randomized 1:1:1 to receive once-daily administration of DS-8500a (either 25 mg, 50 mg, or 75 mg), sitagliptin 50 mg, or placebo for 12 weeks. [EASD 2017, abstract 847]
At week 12, a dose-dependent reduction in HbA1c levels was observed among patients on DS-8500a compared with placebo (-0.21 percent; p=0.0233 for 25 mg, -0.34 percent; p=0.0004 for 50 mg, and -0.45 percent; p<0.0001 for 75 mg).
Compared with placebo, DS-8500a 50 mg and 75 mg also reduced fasting plasma glucose (FPG, -12.7 mg/dL; p=0.0004 and -14.4 mg/dL; p<0.0001, respectively), area under the curve0-3h for glucose during a meal tolerance test (-50.6 mg/dL x h; p=0.0020 and -59.7 mg/dL x h; p=0.0003), and 2-hour postprandial glucose (-18.5 mg/dL; p=0.0102 and -22.0 mg/dL; p=0.0022).
FPG reduction was sustained for up to 12 weeks, said the researchers, which is an improvement from other GPR119 agonists that typically have shorter glucose-lowering effects lasting for up to 2–4 weeks only.
With regards to lipid profile, administration of DS-8500a 50 mg and 75 mg resulted in a significant increase in HDL cholesterol vs placebo (5.9 percent; p=0.0032 and 6.6 percent; p=0.0009, respectively), as well as a significant reduction in total cholesterol (-7.0 percent; p<0.0001 and -6.2 percent; p=0.0002), LDL cholesterol (-7.3 percent; p=0.0044 and -8.1 percent; p=0.0014), and triglycerides (-32.7 percent; p<0.0001 and -30.9 percent; p<0.0001).
Apart from two cases of clinically-relevant drug-related hypoglycaemia in the DS-8500a 50 mg arm, DS-8500a was generally well tolerated with no reports of serious drug-related treatment-emergent adverse events at any dose of DS-8500a.
These results were consistent with the findings of a previous study in another Japanese cohort, [Diabetes 2016;65:abstract 119-LB] providing additional data showing the potential benefit of DS-8500a for T2D, noted the researchers.