sitagliptin-phosphate and Hyperinsulinism

To compare the therapeutic effects between sitagliptin and voglibose both with sensor-augmented insulin pump (SAP) in newly diagnosed type 2 diabetes mellitus (T2DM).. Fifty-six newly diagnosed hospitalized T2DM patients in Department of Endocrinology of the First Affiliated Hospital of Dalian Medical University, with hemoglobin A1c (HbA1c) value of 9%-11%, were randomized into the sitagliptin (S) group (n=28) and the voglibose (V) group (n=28) by block randomisation. Participants in S group received sitagliptin 100 mg per day, and V group received voglibose 0.2 mg for 3 times per day. All patients were treated with SAP for 9 days. Real-time continuous glucose monitoring (RT-CGM) was used. Glucose variability parameters were observed. The research has been approved by the ethics committee of the First Affiliated Hospital of Dalian Medical University(KY2014-08).. No significant differences were observed in baseline characteristics between the two groups (all P>0.05). In V group and S group, fasting blood glucose (FPG) [(6.4±1.1) vs (11.4±3.0) mmol/L, P=0.008; (5.5±0.8) vs (11.0±2.1) mmol/L, P<0.001], mean blood glucose(MBG) [(7.5±0.8) vs (12.0±1.1) mmol/L, P=0.045; (6.7±0.7) vs (12.5±1.3) mmol/L, P=0.002], standard deviation of blood glucose (SDBG) (P=0.023, 0.036) decreased and homeostasis model assessment (HOMA)-β (P=0.002, 0.001) increased significantly after 9 days therapy. The mean of daily differences (MODD)(P=0.027), coefficient of variation-FPG (CV-FPG) (P=0.033) and HOMA-IR (P=0.039) in S group significantly decreased, while postprandial glycemic excursion (PPGE)(P=0.003, 0.026, 0.011, 3 meals respectively)and the low glycemic index(LBGI)(P=0.025) in V group decreased, the peak postprandial level of glucose(Δt)was longer compared with before (P=0.028, 0.026, 0.030, 3 meals respectively). After therapy, PPGE in V group significantly became lower than those in S group (P=0.041, 0.032, 0.036, 3 meals respectively), while FPG and MBG in S group were significantly lower than those in V group (P=0.041, 0.039).. Sitagliptin or voglibose combined with SAP can improve glucose control and protect islet function for patients with newly diagnosed T2DM. Sitagliptin has advantages in controlling MBG and FPG compared with voglibose. Voglibose has more striking advantages in reducing the postprandial blood glucose fluctuation.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Glucose; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Hyperinsulinism; Inositol; Insulin Infusion Systems; Insulins; Postprandial Period; Sitagliptin Phosphate

Pharmacological approaches that enhance incretin action for the treatment of type 2 diabetes mellitus have recently been developed, i.e. injectable glucagon-like peptide-1 receptor (GLP-1R) agonists with prolonged plasma half-lives and orally available inhibitors of dipeptidyl peptidase (DPP)-4, the main enzyme responsible for the rapid degradation of circulating glucagon-like peptide-1 and glucose-dependent insulinotropic peptide. The mechanism(s) underlying the glucose-lowering effect of these two pharmacotherapies differs and is not yet fully understood. Here we investigated whether acute GLP-1R activation (exendin-4) or DPP-4 inhibition (des-F-sitagliptin) modulates insulin action in mice using a hyperinsulinemic euglycemic clamp. A single iv bolus of des-F-sitagliptin (11 mg/kg) was administered to mice 15 min after the start of the clamp, and its effect was compared with a 50-ng bolus of exendin-4 or the same volume of saline. Despite matched levels of plasma glucose and insulin, within 15 min the glucose infusion rate required to maintain euglycemia was significantly greater after des-F-sitagliptin compared with saline or exendin-4. This difference was entirely due to enhancement of insulin-mediated suppression of endogenous glucose production by des-F-sitagliptin, with no difference in glucose disposal rate. These findings illustrate that DPP-4 inhibition modulates glucose homeostasis through pathways distinct from those used by GLP-1R agonists in mice.

Topics: Animals; Blood Glucose; Body Weight; Dipeptidyl-Peptidase IV Inhibitors; Exenatide; Glucose Clamp Technique; Glucose Tolerance Test; Hyperinsulinism; Hypoglycemic Agents; Insulin; Insulin Secretion; Male; Mice; Mice, Inbred C57BL; Peptides; Pyrazines; Sitagliptin Phosphate; Triazoles; Venoms

We sought to establish the extent and mechanisms by which sitagliptin and metformin singly and in combination modify islet disease progression in human islet amyloid polypeptide transgenic (HIP) rats, a model for type 2 diabetes.. HIP rats were treated with sitagliptin, metformin, sitagliptin plus metformin, or no drug as controls for 12 weeks. Fasting blood glucose, insulin sensitivity, and beta-cell mass, function, and turnover were measured in each group.. Sitagliptin plus metformin had synergistic effects to preserve beta-cell mass in HIP rats. Metformin more than sitagliptin inhibited beta-cell apoptosis. Metformin enhanced hepatic insulin sensitivity; sitagliptin enhanced extrahepatic insulin sensitivity with a synergistic effect in combination. beta-Cell function was partially preserved by sitagliptin plus metformin. However, sitagliptin treatment was associated with increased pancreatic ductal turnover, ductal metaplasia, and, in one rat, pancreatitis.. The combination of metformin and sitagliptin had synergistic actions to preserve beta-cell mass and function and enhance insulin sensitivity in the HIP rat model of type 2 diabetes. However, adverse actions of sitagliptin treatment on exocrine pancreas raise concerns that require further evaluation.

Topics: Amyloid; Animals; Animals, Genetically Modified; Arginine; Diabetes Mellitus, Type 2; Disease Models, Animal; Glucose Clamp Technique; Humans; Hyperglycemia; Hyperinsulinism; Hypoglycemic Agents; Islet Amyloid Polypeptide; Islets of Langerhans; Metformin; Pyrazines; Rats; Rats, Sprague-Dawley; Sitagliptin Phosphate; Triazoles