Abstract
Type 2 diabetes mellitus is a complex heterogeneous group of metabolic conditions characterized by increased levels of blood glucose due to impairment in insulin action and/or insulin secretion. Exploring new drug therapies will benefit in preventing morbidity and mortality associated with diabetes as well as the growing health care costs. Sitagliptin is a highly selective DPP-4 inhibitor that has been shown to improve glycemic control and beta cell function. Repaglinide is a short acting insulin sectretagogue stimulating insulin release. The purpose of this study was to evaluate the effect of combining sitagliptin (5 mg/kg) and repaglinide (0.15 mg/kg & 0.3 mg/kg) on improving hyperglycemia and enhancing the pancreatic function in high fat diet/streptozotocin-induced type 2 diabetes mellitus rat model. The current results highlight a significant improvement in glycemic control and pancreatic insulin production upon addition of sitagliptin to repaglinide therapy. Repaglinide either alone or in combination was effective in preserving islet cell integrity. Further, immunohistochemical staining revealed significant higher insulin content in the combination groups compared to corresponding monotherapies. The combination therapy had a positive effect in lowering serum lipids. In conclusion, the present study reinforces the view of using gliptins in combination with repaglinide to enhance the glycemic control and lipid profile in patients with type 2 diabetes.
Highlights
Hyperglycemia and diabetes are important causes of mortality and morbidity worldwide (Danaei et al, 2006)
In patients with type 2 diabetes, the long term treatment with a single antidiabetic drug often results in a poor maintenance of the glycemic control due to the deteriorating β-cell function in addition to the side effects of the existing antidiabetic drugs (Hou et al, 2012)
The current study aimed to investigate the added benefits of combining two antihyperglycemic agents, sitagliptin and repaglinide, in a rat model for type 2 diabetes
Summary
Hyperglycemia and diabetes are important causes of mortality and morbidity worldwide (Danaei et al, 2006). Type 2 diabetes mellitus accounts for 95% of diabetic people around the world (Lysy et al, 2012). It is a chronic metabolic disorder characterized by a progressive decline in insulin action (insulin resistance), followed by the inability of βcells to compensate for insulin resistance (pancreatic β-cell dysfunction) (Li et al, 2008; Gunasekaran and Gannon, 2011; Ashcroft and Rorsman, 2012). Decreased β cell mass resulting from increased apoptosis is an important property of type 2 diabetes (Butler et al, 2003; Marchetti et al, 2010). When considering therapeutic intervention in type 2 diabetes, the agents of choice will be those that stimulate insulin secretion in a glucose dependent manner and maintain or enhance β-cell mass through either increased proliferation or decreased apoptosis
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