磷酸西格列汀对2型糖尿病降糖效果及对胰岛功能的保护作用

目的评价磷酸西格列汀对2型糖尿病患者胰岛功能的保护作用及降糖效果。方法新诊断的2型糖尿病患者60例,随机分为3组,分别给予磷酸西格列汀、磷酸西格列汀联合盐酸二甲双胍和盐酸二甲双胍治疗,为期12周。观察三组治疗前后患者HbA1c和血糖、胰岛素、C肽、胰岛素降糖指数(DI)、胆固醇、三酰甘油、HDL-C、LDL-C等指标的变化。结果磷酸西格列汀治疗后,患者HbA1c、FPG、2hPPG均下降,磷酸西格列汀联合二甲双胍组下降更多,与其他两组比较差异有统计学意义。西格列汀联合二甲双胍组DI上升最明显(P<0.05)。结论西格列汀单药治疗2型糖尿病效果良好并能提高胰岛素降糖指数,但联合二甲双胍效果更强。     

西格列汀联合甘精胰岛素对2型糖尿病患者血糖水平影响观察

摘 要 目的:观察西格列汀联合甘精胰岛素对2型糖尿病患者血糖水平的影响,以及临床疗效和安全性。方法：66例2型糖尿病患者随机分为观察组和对照组,分别给予西格列汀联合甘精胰岛素治疗和预混胰岛素治疗3个月。比较两组患者治疗前后的血糖水平变化,以及血压血脂等指标变化。评价两组临床疗效和药品不良反应。结果：除低血糖AUC外,观察组患者治疗后的空腹血糖、餐后2 h血糖、糖化血红蛋白,以及72 h内平均血糖水平、血糖水平标准差、日内血糖平均波动幅度、日内血糖平均绝对差、日内血糖波动次数、高血糖AUC等血糖指标均较前明显改善（P<0.05）,且优于对照组（P<0.05）。两组患者治疗前后血压、血脂无显著变化（P>0.05),观察组治疗后BMI低于对照组（P<0.05）。两组总有效率比较差异无统计学意义（P>0.05)。观察组药品不良反应发生率显著低于对照组（P<0.05）。结论：西格列汀联合甘精胰岛素能显著降低2型糖尿病患者的血糖水平,疗效确切,安全性高,建议临床推广。     

磷酸西格列汀联合门冬胰岛素30治疗2型糖尿病临床疗效观察

目的：观察磷酸西格列汀联合门冬胰岛素30治疗2型糖尿病的临床疗效与安全性。方法接受门冬胰岛素30治疗的血糖控制不理想的2型糖尿病患者60例,随机分为西格列汀组和二甲双胍组,各30例。西格列汀组给予西格列汀100 mg/d口服,二甲双胍组给予二甲双胍1.0 g/d,两组根据血糖监测情况适时调整门冬胰岛素30用量,疗程12周。检测两组用药前后空腹血糖(FPG),餐后2 h血糖(2 h PG),糖化血红蛋白(HbA1c),观察不良反应。结果西格列汀组完成29例,二甲双胍组完成28例。两组患者的空腹血糖、餐后2 h血糖及糖化血红蛋白值均较治疗前明显下降,差异有统计学意义(P<0.05);治疗后两组比较,西格列汀组优于二甲双胍组(P<0.05)。均无严重不良反应。结论磷酸西格列汀联合门冬胰岛素30治疗2型糖尿病有明显疗效,可以更好控制血糖,无明显不良反应,耐受性好。     

单用二甲双胍血糖控制不佳的2型糖尿病患者加用西格列汀及护理干预后的疗效观察

目的观察单用二甲双胍血糖控制不佳的2型糖尿病患者加用西格列汀并联合护理干预对患者血糖改善及生活质量的影响。方法选择2013年5-9月来我院就诊的单用二甲双胍至少1 500 mg/d治疗3个月以上,血糖控制不佳的2型糖尿病患者27例,加用西格列汀100 mg/d,持续治疗16周,并进行护理干预,观察治疗前后空腹血糖(FPG)、糖化血红蛋白(Hb A1c)、低密度胆固醇(LDL)的变化情况。结果加用西格列汀治疗并联合护理干预16周后,患者FPG、Hb A1c较治疗前显著下降(P<0.05),但LDL无显著变化(P>0.05),16周治疗期间无严重不良反应发生。结论对单用二甲双胍血糖控制不佳的2型糖尿病患者加用西格列汀及相应的护理干预措施后,血糖控制安全、有效,耐受性好。     

Sitagliptin and the risk of hospitalization for heart failure: A population-based study

Background

Saxagliptin was associated with an increased risk of hospitalization for heart failure (HHF) in diabetic patients with high cardiovascular risk. This study assessed the risk of HHF during an exposure to sitagliptin in general diabetic patients.

Methods

In Taiwan National Health Insurance research database, a study of the beneficiaries aged ≥ 45 years with diabetes treated with or without sitagliptin between March 2009 and July 2011 was conducted. Patients treated with sitagliptin were matched to patients never exposed to a dipeptidyl peptidase-4 (DPP-4) inhibitor by the propensity score methodology. The outcome measures were the first and the total number of HHF, and mortality for heart failure or all causes.

Results

A total of 8288 matched pairs of patients were analyzed. During a median of 1.5 years, the first event of HHF occurred in 339 patients with sitagliptin and 275 patients never exposed to a DPP-4 inhibitor (hazard ratio: 1.21, 95% confidence interval: 1.04–1.42, P = 0.017); all-cause mortality was similar (hazard ratio: 0.87, 95% confidence interval: 0.74–1.03, P = 0.109). The risk for HHF was proportional to exposure (hazard ratio: 1.09, 95% confidence interval: 1.06–1.11, P < 0.001 for every 10% increase in adherence to sitagliptin). Overall, there were 935 events of HHF, in which the association between the number of HHF and the adherence to sitagliptin was linear. The greatest total number of HHF occurred in the patients with the highest adherence.

Conclusions

The use of sitagliptin was associated with a higher risk of HHF but no excessive risk for mortality was observed.     

Sitagliptin attenuates methionine/choline-deficient diet-induced steatohepatitis

Aims

Accumulating evidence suggests that inhibitors of dipeptidyl peptidase-4 (DPP-4), such as sitagliptin, may play an important role in the prevention of non-alcoholic steatohepatitis (NASH). This study was conducted to elucidate whether sitagliptin could prevent steatohepatitis by inhibiting pathways involved in hepatic steatosis, inflammation, and fibrosis.

Methods

C57BL/6 mice were fed a methionine/choline-deficient (MCD) diet with or without supplement with sitagliptin for 5 weeks. Liver and adipose tissue from mice were examined histologically and immunohistochemically to estimate the effect of sitagliptin on the development of NASH.

Results

Supplementation with sitagliptin resulted in significant improvement of MCD diet-induced fat accumulation in the liver. In addition, sitagliptin treatment lowered fatty acid uptake, expression of VLDL receptor and hepatic triglyceride content. Sitagliptin also effectively attenuated MCD diet-induced hepatic inflammation, endoplasmic reticulum (ER) stress, and liver injury, as evidenced by reduced proinflammatory cytokine levels, ER stress markers, and TUNEL staining. Expression of CYP2E1 and 4NHE were strongly increased by the MCD diet, but this effect was successfully prevented by sitagliptin treatment. Furthermore, sitagliptin significantly decreased levels of MCD diet-induced fibrosis-associated proteins such as fibronectin and α-SMA in the liver. Inflammatory and atrophic changes of adipose tissue by MCD diet were restored by sitagliptin treatment.

Conclusions

Sitagliptin attenuated MCD diet-induced hepatic steatosis, inflammation, and fibrosis in mice through amelioration of mechanisms responsible for the development of NASH, including CD36 expression, NF-κB activation, ER stress, CYP2E1 expression, and lipid peroxidation. Treatment with sitagliptin may represent an effective approach for the prevention and treatment of NASH.     

西格列汀治疗合并糖调节受损的肥胖患者的疗效分析

目的:观察西格列汀对肥胖合并糖调节受损患者的胰岛功能、血糖、体重指数、腰围等指标影响,探讨西格列汀在糖尿病预防及早期治疗方面的作用。方法:选取2011年6月²013年11月首次门诊就诊于泉州市第一医院内分泌科的70例糖调节受损(IGR)患者,年龄(48.61±5.07)岁,未经过任何调脂、降糖及其他治疗。随机分为两组,即A组(35例):进行糖尿病、低脂饮食,运动锻炼;B组(35例):同样进行饮食控制、体育锻炼(同A组),同时加用西格列汀100 mg,qd;6个月后,观察空腹血糖(FBG)、餐后2 h血糖(2 h PG)、空腹血清胰岛素、餐后2 h血清胰岛素、胰岛素抵抗指数(HOMA-IR)、腰围、体重指数(BMI)等指标的变化。结果:A组入组后6个月,空腹及餐后2 h血清胰岛素水平、HOMA-IR无明显变化,差异无统计学意义;空腹及餐后2 h血糖、BMI、腰围水平显著降低,差异有统计学意义(P<0.05)。B组治疗后,空腹及餐后2 h血糖、空腹及餐后2 h血清胰岛素水平、HOMA-IR、BMI、腰围水平均显著降低,差异有统计学意义(P<0.01)。结论:西格列汀具有明显的降低高胰岛素血症及改善胰岛素抵抗的作用。     

Efficacy and safety of sitagliptin monotherapy and combination therapy in Japanese type 2 diabetes patients

(J Diabetes Invest, doi: 10.1111/j.2040‐1124.2012.00221.x, 2012) Aims/Introduction: To determine the efficacy and safety of sitagliptin monotherapy and combination therapy in Japanese type 2 diabetes patients after 3 months’ therapy. Materials and Methods: A retrospective, observational study of 741 type 2 diabetes patients was carried out; 110 received sitagliptin monotherapy, and 631 received combination therapy with sitagliptin when other oral medications were insufficient. The primary outcome measure was glycated hemoglobin (HbA_1c) measured at 0, 4 and 12 weeks of sitagliptin therapy. Results: In the monotherapy and combination therapy groups, HbA_1c decreased significantly after 12 weeks. Target HbA_1c (<7%) was achieved in 39.1% overall. On logistic regression analysis, baseline HbA_1c was the strongest contributing factor for achieving target HbA_1c; baseline body mass index and duration of diabetes were also significant factors. A total of 82 patients (11%) were unresponsive to sitagliptin. These patients’ baseline body mass index was significantly higher and their baseline HbA_1c was significantly lower than those of patients who responded to sitagliptin. The most commonly co‐administered drugs were sulfonylureas (508 patients). In these patients, the dose of sulfonylurea decreased with time. In 66 patients whose sulfonylurea dosage was reduced when sitagliptin was started, HbA_1c and bodyweight decreased significantly after 12 weeks. A total of 24 patients receiving sulfonylureas had mild hypoglycemia, but none discontinued sitagliptin. Conclusions: Sitagliptin was effective and safe as both monotherapy and combination therapy in Japanese type 2 diabetes patients. When sulfonylureas were ineffective, sitagliptin improved glycemic control. In patients whose sulfonylurea dose was reduced at the start of sitagliptin, blood glucose improved and bodyweight decreased after 12 weeks.