Comparing hypoglycemic activity of novel GPR119 agonist and DPP-4 inhibitor sitagliptin

Hypoglycemic drugs affecting the incretin system increasingly becoming popular because of its high safety and efficacy. The regulation of the secretion of endogenous incretin involves a number of receptors on the enteroendocrine cells, among which the most promising is GPR119. After activation it increases the incretins secretion and glucose-dependent insulin secretion, that is important from the point of view of effective control of postprandial glucose levels with minimal risk of hypoglycemia.

Aims.

To conduct a comparative study of hypoglycemic activity of DPP-4 inhibitors (sitagliptin) and novel GPR119 agonist receptor — compound ZB-16 in streptozotocin-nicotinamide-induced rat model of type 2 diabetes mellitus (T2DM).

Material and methods.

The hypoglycemic effect of ZB-16 (0.1 and 1 mg/kg per os) and sitagliptin (10 mg/kg per os) was studied during 4-week administration in 50 adult female rats (6 months, 240—260 g) with streptozotocin-nicotinamide-induced T2DM. The oral glucose tolerance test (OGTT) was performed on the 14th and 28th day after the start of treatment.

Results.

Animals receiving compound ZB-16 at a dose of 1 mg/kg by the end of treatment there have a significant reduction in fasting glucose as compared with the control group (7.9±0.43 and 0.54±9,6 mmol/l, respectively). During the OGTT on day 28 of treatment compound ZB-16 improves the rate of glucose utilization, reducing «peak» of growth glycemia (15,7±0,88 versus 21,6±1,06 mmol/L) and area under the curve «glucose concentration-time» (to 25%) compared with the control group during the OGTT.

Conclusions.

Novel GPR119 agonist — ZB-16 (1 mg/kg) has a clear hypoglycemic effect comparable to that of sitagliptin in rats with streptozotocin-nicotinamide-induced T2DM.

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