| Background and ObjectiveType 2 diabetes mellitus (T2DM) was a chronic progressive disease. with the prolongation of the course of disease, function ofβ-cell diminishes gradually, the number ofβcells declines in its performance. For the patients of overweight or obesity with type 2 diabetes mellitus, the majority of patients were accompanied by insulin resistance. Therefore, we will take treatment to protecβ-cell function and reduce insulin resistance in this crowd of the patients ,the patients can benefit more from treatment. And many studies have confirmed that glucagon-like peptide -1 (GLP-1), a polypeptide incretion hormone secreting from intestinal mucosa L-cell can promote ? cell proliferation and inhibit its apoptosis so as to enhance the quality and function of ? cell. therefore, it results in increasing insulin secretion to regulate glucose metabolism .Besides delaying gastric emptying and reducing intestine peristalsis. GLP-1 can also specially activate the hypothalamic nuclei to produces satiety, suppress appetite, causing weight loss, thereby improving insulin resistance. Based on its characteristics above and reducing effect of incretin in patients with T2DM, so that GLP-1 receptor agonist- exenatide can be used by patients of T2DM in clinical treatment.Many clinical trials on exenatide have indicated that exenatide with metformin and /or sulfonylurea drugs in patients with T2DM can effectively control blood sugar levels as well as lost weight.at the same time, it can improveβ-cell function and insulin resistance. But the subjects of these trials were mostly European and American populations, the clinical study in patients of overweight or obesity with T2DM with exenatide and other antidiabetic drugs has not been reported. We have choosed the patients of overweight or obeseity with T2DM inadequately controlled with metformin and other antidiabetic drugs , using controll study of the treatment group by itself , we will evaluate its clinical efficacy and safety with metformin and exenatide, or adding to insulintropic drugs after the treatment of 16 weeks.Materials and methodsThis study was a single center, open trial. Subjects of recruitment were outpatinet patients in Endocrinology department of Guangdong Provincial People's Hospital between September 2009 and November 2010: (1) the patients have been diagnosed as T2DM by the diagnostic criteria of T2DM in WHO of1999; (2) metformin (daily dose of≥500mg) combined with other antidiabetic drugs for 3 months or more; (3) FPG> 7.0mmol / L, or 7.0%≤HBA1c≤10%; (4) overweight or obesity (according to the 2003 "Chinese adults overweight and Obesity Prevention and Control Guide " BMI≥24 kg / m2 as overweight, BMI≥28kg / m2 as obesity); (5) the patients who are willing to sign informed consent. After all the patients entered into groups: the foregoing dose of metformin was the same, insulintropic agents should be maintained if the patient were using it , and other antidiabetic drugs were stopped using. Then added with exenatide (5ug / time, 2 times / daily, subcutaneous injection) treatment for 4 weeks , increasing the dose (10ug / time, 2 times / daily, subcutaneous injection) for 12 weeks.The patients must be visited every 4 weeks (we call up the patients in the midt of two visits), their height (H), body weight (W), blood pressure (SBP / DBP) were measured during each visit, while observing the following indicators: (1) glucose metabolism indicators (FPG, 2h PPG, HbA1c); (2) islet B cell function indicators (insulin secretion index HOMA-% B); (3) insulin resistance indicators (BMI, BMI = W/H2, Wt, insulin resistance index HOMA-IR). On the beginning and endpoint of the trial, safety indicators were observed: adverse events, hypoglycemia, serum amylase (such as abdominal pain of patients , adding to measure serum amylase), and renal function (age≥65 years , or patients with mild liver or renal insufficiency, must be required to monitor liver and kidney function at each visit). When it occurred during of treatment :patients with blood glucose <3.9mmol/l or the symptomatic hypoglycemia ,we will adjust the program of treatment: (1) the patients are using insulintropic agent, first adjusting doses of it. (2) if they have not used insulintropic agent, reducing dose of metformin. During the test, if fasting CBG> 6.1mmmol / L for 3 days continuously, or postprandial CBG> 11.1mmol / L; or increasing HbA1C accured; increasing the dose of oral antidiabetic drugs or other antidiabetic drugs is considered a violation of research programs .the patients must be withdrew from the study. In principle, HBA1c <7.0% for the goal value, in the special cases, some patients may reach to individual goals. SPSS16.0 were used for statistical analysis.The data is calculated and analyzed by SPSS 16.0. Data with normal distribution was expressed as means±standard deviation. paired t test or Wilcoxon signed rank test are used to compare data analysis. For the differential analysis of the correlation between before and after treatment, Pearson or Spearman correlation analysis is applied. Statistics difference is presented by P<0.05.ResultsThis study has enrolled 22 patients. 14 patients (10 men, 4 women) have completed the trial ,in which 8 patients have withdrew from the study (1 case of adverse events, 2 patients have lost ,5 patients have violated program of research).⑴After treatment of 16 weeks, compared with baseline, the decrease of HbA1c (6.99±0.83 VS 8.04±0.89)% exitsts in statistical difference (P<0.05), degree of decrease as ( X [95% CI]) (-1.05 [-1.36, -0.73]%). Descent of 2h PPG (8.40±2.63 VS 13.32±4.74) mmol / l exists in statistical difference too (P <0.05), degree of decrease as (-4.92 [-8.07, -1.76] mmol / l). there is not statistical difference in FPG before and after treatment (P>0.05). Pearson correlation analysis has showed: After treatment, difference of HbA1c and 2h PPG are positive correlation (r = 0.024, P>0.05), but no statistical significant.⑵At the endpoint of treatment, HOMA-% B and HbA1c are compared by their treatment of 4 weeks repectively, the decrease of HbA1c (6.99±0.83 VS 7.50±0.86)% has statistical significant (P<0.05), degree of decrease (-0.51 [-0.83, -0.1]%). HOMA-% B (104.3±44.8 VS 86.9±30.2) is higher (P<0.05). Spearman correlation analysis has showed that: difference of HbA1c and HOMA-% B are negative correlation (r = -0.655, P <0.05).⑶At the endpoint of treatment, compared with the baseline, the decrease of BMI and Wt have statistical significant (P <0.05), degree of decrease (-1.78 [-2.33, -1.24] kg/m2), (-5.0 [-6.9, -3.1] cm) respectively. Spearman correlation analysis has showed that : difference of BMI and Wt are positive correlation before and after treatment (r = 0.789, P <0.05). Compared with the treatment of 4 weeks, the decrease of HOMA-IR has statistical significance (P <0.05) at the end of the trial.⑷At the endpoint of study, compared with the beginning of treatment, blood pressure,serum amylase and other biochemical indicators have no statistical significance (P> 0.05). the most common adverse events is nausea (50%), generally mild to moderate nausea; a headache in 2 patients (9.0%); 1 case of hypoglycemia (4.5%) in all patients enrolled in the study.ConclusionWhen the patients of overweight or obesity with T2DM were treated with exenatide and Metformin, or adding with insulinotropic drugs in this study:⑴Their postprandial blood glucose and HbA1c are significantly reduced in the patients of overweight or obesity with T2DM after treatment .⑵Their HOMA-%B has been increased, it suggests that it may be to improve the function of ? cells.⑶Their body mass index,waist circumference and HOMA-IR have been reduced ,it suggests that it may improve insulin resistance.⑷The most common adverse event is mild or moderate nausea generally , which could be tolerated.
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