艾塞那肽治疗2型糖尿病的有效性及安全性研究
摘要
目的：探讨血糖控制不佳的2型糖尿病患者使用艾塞那肽的有效性及安全性。方法：随机选取于新疆自治区人民医院内分泌科门诊及病区就诊的12例血糖控制欠佳、血清C肽正常并且确诊为2型糖尿病的患者,给予艾塞那肽5μg每日2次治疗4周,随后改为10μg每日2次治疗20周,观察该药的临床疗效和安全性。结果：1.艾塞那肽治疗后患者体重持续减轻(较基线下降2.2kg,P<0.05),体重指数(BMI)、腰臀围比(WHR)和腹围降低(P<0.05)；2.糖化血红蛋白(HbA1c)、空腹血糖(FBG)、空腹胰岛素(FINS)、胰岛素抵抗指数(HOMA-IR)降低(P<0.05),空腹C肽(FCP)、胰岛8细胞功能指数(HOMA-B)升高(P<0.05)；3.治疗前后血脂谱、血压无显著变化；4.日间血糖平均绝对差(MODD)、日内平均血糖波动幅度(MAGE)餐后血糖达峰时间(At),餐后血糖漂移幅度(PPGE)等动态血糖监测指标均降低(P<0.05),日内血糖波动次数(NGE)治疗前后无差异；5.艾塞那肽耐受性良好,最常见的不良事件是轻到中度的胃肠道反应。轻度至中度低血糖事件发生率低,无严重低血糖事件。结论：本次研究表明艾塞那肽可以在短期内改善血清C肽正常的2型糖尿病患者的HbA1c、FBG和餐后血糖水平,减轻血糖波动,改善胰岛β细胞功能,所有患者均有体重减轻。不良反应轻,主要表现在轻度胃肠道反应与轻度低血糖事件,但其远期疗效及安全性尚需进一步观察。
Objective:To evaluate the efficacy and safety of exenatide in patients with type2 diabetes (T2D) inadequately controlled with oral agents. Methods:Randomly selected 12 T2D patients with normal serum c-peptide and suboptimally controlled blood glucose in the Xinjiang Autonomous Region People's Hospital of Endocrinology outpatient clinics and ward. All the patients received exenatide 5μg tiwce-daily for 4 weeks then 10μg tiwce-daily for 20 weeks to evaluate the efficacy and safety. Results:1.Exenatide progressively reduced body weight from baseline (-2.2kg at 24 weeks,p<0.05). There was a significant decrease in Body Mass Index (BMI), Waist/Hip Ratio(WHR) and Abdominal girth (P<0.05) after exenatide treatment for 24weeks; 2.Significant differences in glycosylated hemoglobin (HbAlc), fasting blood glucose (FBG), fasting insulin (FINS), fasting C-peptide (FCP), homeostasis model assessment-insulin resistance (HOMA-IR) and HOMA-B change from baseline were observed; 3.However, there was no significant difference in serum lipids and blood pressure; 4.Absolute means of daily difference (MODD), mean of amplitude glycemic excursions(MAGE), postprandial glycimic excursions (PPGE) and the time of reaching postprandial peak glucose(At) were significant decreased afeter exenatide treatment. Number of glycimic excursions(NGE) was no significant difference; 5.Exenatide was generally well tolerated. The most frequent adverse events were gastrointestinal in nature and generally mild to moderate. Incident of mild to moderate hypoglycemia was low, with no severe hypoglycemia.Conclusion:In these T2D patients with normal serum c-peptide, exenatide treatment was associated with improved HbAlc, FBG, improved postprandial glucose control, reduced weight and glycemic excursions, improved P-cell function, and was well tolerated. But the long-time implications of the efficacy and safety with exenatide have yet to be difined.
Objective:To evaluate the efficacy and safety of exenatide in patients with type2 diabetes (T2D) inadequately controlled with oral agents. Methods:Randomly selected 12 T2D patients with normal serum c-peptide and suboptimally controlled blood glucose in the Xinjiang Autonomous Region People's Hospital of Endocrinology outpatient clinics and ward. All the patients received exenatide 5μg tiwce-daily for 4 weeks then 10μg tiwce-daily for 20 weeks to evaluate the efficacy and safety. Results:1.Exenatide progressively reduced body weight from baseline (-2.2kg at 24 weeks,p<0.05). There was a significant decrease in Body Mass Index (BMI), Waist/Hip Ratio(WHR) and Abdominal girth (P<0.05) after exenatide treatment for 24weeks; 2.Significant differences in glycosylated hemoglobin (HbAlc), fasting blood glucose (FBG), fasting insulin (FINS), fasting C-peptide (FCP), homeostasis model assessment-insulin resistance (HOMA-IR) and HOMA-B change from baseline were observed; 3.However, there was no significant difference in serum lipids and blood pressure; 4.Absolute means of daily difference (MODD), mean of amplitude glycemic excursions(MAGE), postprandial glycimic excursions (PPGE) and the time of reaching postprandial peak glucose(At) were significant decreased afeter exenatide treatment. Number of glycimic excursions(NGE) was no significant difference; 5.Exenatide was generally well tolerated. The most frequent adverse events were gastrointestinal in nature and generally mild to moderate. Incident of mild to moderate hypoglycemia was low, with no severe hypoglycemia.Conclusion:In these T2D patients with normal serum c-peptide, exenatide treatment was associated with improved HbAlc, FBG, improved postprandial glucose control, reduced weight and glycemic excursions, improved P-cell function, and was well tolerated. But the long-time implications of the efficacy and safety with exenatide have yet to be difined.
引文
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[3]Anderson JW, Kendall CW, Jenkins DJ. Importance of weight management in type 2 diabetes:review with meta-analysis of clinical studies[J]. J Am Coll Nutr, 2003,22:331-339.
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[13]Hernandez-Diaz S, Adami HO. Diabetes therapy and cancer risk:causal effects and other plausible explanations [J]. Diabetologia,2010,53(5):802.
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[15]Cornu M, Modi H, Kawamori D, et al. Glucagon-like peptide-1 increases beta-cell glucose competence and proliferation by translational induction of insulin-like growth factor-1 receptor expression[J]. J Biol Chem,2010,285:10538-10545.
[16]Wenn DM, WintleM, Malone JK. Exenatide effects on glucose metabolism and metabolic disorders common to overweight and obese patients with type 2 diabetes[J]. Drug Devel Res,2006,67:666-676.
[17]Nauck MA, Duran S, Kim D, et al. A comparison of twicedaily exenatide and biphasic insulin aspart in patients with type 2 diabetes who were suboptimally controlled with sulfonylurea and metformin:a noninferiority study[J]. Diabetologia, 2007,50:259-267.
[18]Zinman B, Hoogwerf BJ, Garcia SD, et al. The effect of adding exenatide to a t hiazolidinedione in suboptimally controlled type 2 diabetes[J]. Ann Intern Med,2007, 146:477-485.
[19]Mack CM, Laugero BJ, Liu Q, et al. Therapeutic applications of incretin mimetics for metabolic diseases:preclinical studies[J]. Drug Dev Res,2006,67:553-558.
[20]Arakawa M, Ebato C, Mita T, et al. Effects of exendin-4 on glucose tolerance, insulin secretion, and beta—cell proliferation depend on treatment dose, treatment duration and meal contents[J]. Biochem Biophys Res Commun,2009,390:809-814.
[21]Deacon CF. Dipeptidyl peptidase 4 inhibition with sitagliptin:a new therapy for Type 2 diabetes[J]. Expert Opin Investig Drugs,2007,16:533-545.
[22]Vilsboll T. The effects of glucagon-like peptide-1 on the beta cell[J]. Diabetes Obes Metab,2009,11(3):11-18.
[23]Bradley DP, Kulstad R, Schoeller DA. Exenatide and weight loss[J]. Nutrition,2010, 26:243-249.
[24]Gedulin BR, Nikoulina SE, Smith PA, et al. Exenatide(exendin-4) improves insulin sensitivity and β-cell mass in insulin-resistant obese fa/fa Zucker rats independent of glycemia and boby weight[J]. Endocrinology,2005,146:2069-2076.
[25]Doyle ME, Egan JM. Mechanisms of action of glucagon-like peptide-1 in the pancreas[J]. Pharmacol Ther,2007,113(3):546-593.
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