| [Background]Diabetes is one of the major diseases affecting human health, according to IDF study[1], there is366million patients with diabetes around world, most of them living in developing countries. Current investigation in our counter show that the morbidity of diabetes in adults is as high as9.7%[3]. diabetes became a serious issue for public health.Drug therapy is one of most important parts for diabetes treatment system. Traditional anti-diabetes medicine includes OADs and insulin. The efficacy of these drugs is quite good but it still have several limitations, including body weight gain, hypoglycemia, gastrointestinal effects. Furthermore, Some large RCT research such as UKPDS showed that glucose management could reduce the incidence of diabetic complications significantly, but it could not revise the progress of islet β cell dysfunction. To face this challenge, incretin class drugs becomes our new hope.Incretin class drugs is new hotspot for anti-diabetic medicine research, it can be divided to Glucagon-like peptide l(GLP-1) analogue and Dipeptidyl Peptidase4(DPP-4) inhibitor. Sitagliptin is the first DPP-4inhibitor, it can reduce the degradation of GLP-1and GIP by inhibit the activity of Dipeptidyl Peptidase4, then rise the concentration of GLP-1and GIP indirectly and stimulates secretion of insulin. Studies in foreign countries proved that sitagliptin not only has a great efficacy and safety on diabetes, but also a weight neutral drug.There are a lot of studies involves sitagliptin in western countries. however, due to the rarely use of a glycosidase inhibitor(GSDI) in these places, research data focus on the comparison sitagliptin and a glycosidase inhibitor(GSDI) is limited. As one of the most common use GSDI in China, acarbose plays a key in anti-diabetic treatment. Despite the great efficacy, acarbose has several advantages, such as well tolerance, low hypoglycemia incidence. To compare the efficacy and effect on body weight, we choose acrabose as a positive-control. We hope we can find some novel relationship between sitagliptin and gastrointestinal hormones by this study.[Objective]Comparison effects of sitagliptin and acarbose short-term monotherapy on HbA1c>6.5%and<10.0%of drug-free type2diabetes (T2DM) patients by blood lipids, blood glucose, islet P cell secretory function, body weight and other parameters[Subjects and Methods]1.Subjects and sub-groups:WHO1999years by diagnostic criteria for diabetes and sub-type, screening out of HbAlc>6.5%and<10.0%of patients had not received oral hypoglycemic drugs, lipid-lowering drugs or insulin therapy in6weeks. Research subjects will be randomly divided into two groups:①Sitaglitin treatment group:22cases,12cases of male, female9cases, both from July,2010to April2011, patients with type2diabetes who visit in or out-patient division at endocrinology department in Nanfang hospital were continuously recruited.②Acarbose treatment group:18cases,11cases of male, female7cases, patients were recruited in the same period.All subjects except for the following diseases:acute myocardial infarction, acute and chronic heart failure, acute and chronic arrhythmia, unstable angina pectoris; cerebral infarction, cerebral hemorrhage; liver, renal insufficiency; acute and chronic infections, tumor, connective tissue disease; acute complications of diabetes. Surgery did not exist and other stress situations. Female in lactation period or gestation period, and has a pregnancy plan in study period.The last two months or the current study did not use prohibited drugs:such as systemic corticosteroid therapy, immunosuppressive agents or cytotoxic therapy or the use of vitamin C, E and aspirin, such as the impact of oxidative stress or inflammation drugs.2.Methods:①Before treatment:All patients were in outpatient treatment, and with the consent of the patients agreed to conduct diabetes education, and ask medical history, physical examination, recording age, sex, measured height, weight, waist circumference, hip circumference, blood pressure. Finish examination (blood glucose, insulin, ghrelin, gastrin level after standard meal, serum lipids, HbAlc and superoxide dismutase (SOD).②Intensive Therapy:a fasting blood glucose (FBG)<6.1mmol/L for glucose control objectives. The dose of Sitagliptin which is100mg once a day was not adjusted in treatment. Dose of acarbose was adjusted as follows:Starting dose was50mg,3times a day. If the FPG>6.1mmol/L in visits, the dose can be raised until the maximum dose reached(100mg3times a day).If hypoglycemia happened(FPG<3.9mmol/L), the dose can be reduced until starting dose reached. The drug administration starts in0day of follow-up and ends in the last day of the90days follow-up.③Observed during treatment:Subjects were required to monitor the peripheral blood glucose, in the baseline,4,8,12weeks after treatment follow-up, clinical follow-up each time for3consecutive days before the early morning fasting blood glucose monitoring in order to refer to peripheral blood for three consecutive days the mean FBG<6.1mmol/L for blood glucose control standard. The events may related to low blood glucose-related symptoms were recorded in visits.3. Statistical treatment:All treatment were statistically at the completion of SPSS13.0software. Continuous variables were expressed as mean±SD, and categorical variables were expressed as percentages. Student’s t-test, two independent samples t tests and the Chi-square test were used to compare the difference in the continuous and categorical variables. Otherwise, the nonparametric data line paired Wilcoxon signed rank test or Mann-Whitney’s U-test was performed.[Results]1. Baseline parameters in the two groups including blood glucose, blood lipids and SOD were compared and with good comparability (P>0.05). The difference of these parameters between two group2. After12weeks of treatment, FPG,2hPG, HbA1c and the area under curve of glucose after standard meal were significantly reduced in both groups, the difference was statistically significant (P<0.01). And there was not statistically significant difference (P>0.05)between two groups in these parameters. There is one confirmed hypoglycemia (blood glucose<3.9mmol/L) case in sitagliptin group and no confirmed hypoglycemia case in acarbose group.3. There was no statistically significant difference (P>0.05) of lipid profiles in sitagliptin group after treatment. Total cholesterol was found to be significantly reduced in acarbose after treatment(P<0.05),there was no statistically significant difference (P>0.05) in other lipid parameters.4.There was no statistically significant difference (P>0.05) of fast and2h insulin level in sitagliptin group. Opposite to fast insulin level,2h insulin level was found to be significantly reduced in acarbose after treatment(P<0.05). There was no statistically significant difference (P>0.05) of AUC-Ins in both groups. Homa-β but not Homa-IR parameter was found to be increased in sitagliptin group(P<0.01). Opposites finding was found in acarbose group.5.The rate reached the goal of HbAlc(<7.0%) was similar in both groups, There was no statistically significant difference (P>0.05).6. After12weeks treatment, body weight and BMI was significant reduced in both group(P<0.05).There was no statistically significant difference (P>0.05) of these parameters between two groups. SBP and DBE was found to be significantly reduced in sitagliptin group after treatment(P<0.01).There was no statistically significant difference (P>0.05) of SBP but not DBP in acarbose group.7. There was no statistically significant difference (P>0.05) of SOD in both groups.[Conclusion]Of HbA1c>6.5%and<10.0%of drug-free patients with T2DM1. Both sitagliptin and acarbose monotherapy has a great effects on blood glucose management and blood lipid control with a low incidence of hypoglycemia and well tolerance.2. Although there was no statistically significant difference between two groups(P>0.05), more patients reached the HbA1c control goal in sitagliptin group.3.Acarbose monotherapy can independently improves lipid profile in T2DM patients.4.Both of these drugs can improve islet β cell function and insulin resistance in patients.5.Mild body weight decreased was found in two groups, sitagliptin monotherapy can improves blood pressure level in T2DM patients.6.Sitagliptin monotherapy can significantly reduce fast and after meal ghrelin level in T2DM patients, these findings suggest some special novel advantage of sitagliptin.[Objective]Select ghrelin and gastrin as observation endpoints to analysis the relationship between gastrointestinal hormone and two OADs. Explans the advantages and parts of pharmacological actions of sitagliptin by these relationship.[Subjects and Methods]See Part Ⅰ[Results]There was no statistically significant difference (P>0.05) of baseline fast and2h ghrelin or gastrin in both groups. After12weeks of treatment, fast,2h and the area under curve of ghrelin after standard meal were significantly reduced in sitagliptin group(P<0.05), and no difference was found in gastrin level(P>0.05).Unlike the sitagliptin group,2h and the area under curve of gastrin after standard meal were significantly reduced in acarbose group(P<0.05).No difference of ghrelin level was foud in acarbose group(P>0.05)[Conclusion] Of HbA1c>6.5%and<10.0%of drug-free patients with T2DMSitagliptin monotherapy can significantly reduce fast and after meal ghrelin level in T2DM patients, these findings suggest some special novel advantage of sitagliptin. |
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