Low-Dose Otelixizumab Anti-CD3 Monoclonal Antibody DEFEND-1 Study: Results of the Randomized Phase III Study in Recent-Onset Human Type 1 Diabetes

OBJECTIVE

Previous studies demonstrated that the anti-CD3 monoclonal antibody otelixizumab, administered at a total dose of 48–64 mg, can slow the loss of C-peptide in recent-onset type 1 diabetes patients, with frequent reactivation of Epstein Barr virus (EBV). The DEFEND-1 (Durable Response Therapy Evaluation for Early or New-Onset Type 1 Diabetes) trial was designed to test whether a lower dose of otelixizumab could preserve C-peptide secretion in new-onset type 1 diabetes patients.

RESEARCH DESIGN AND METHODS

A multicenter, randomized, placebo-controlled trial was performed in sites in the U.S., Canada, and Europe. Two hundred eighty-one patients were randomized to treatment with 3.1 mg otelixizumab administered over 8 days or placebo. The primary end point of the study was the change in C-peptide area under the curve (AUC) from a 2-h mixed-meal tolerance test at month 12.

RESULTS

The change in 2-h C-peptide AUC was not different between placebo-treated patients and otelixizumab-treated patients (−0.20 vs. −0.22 nmol/L, P = 0.81). Secondary end points, including HbA_1c, glucose variability, and insulin dose, were also not statistically different between the two groups. More patients in the otelixizumab group than in the placebo group experienced adverse events, mostly grade 1 or grade 2. There was no EBV reactivation (viral load >10,000 copies/10⁶ peripheral blood mononuclear cells) in the otelixizumab group, in contrast with previously published studies at higher doses of otelixizumab.

CONCLUSIONS

Otelixizumab was well tolerated in patients with recent-onset type 1 diabetes at a total dose of 3.1 mg, but did not achieve preservation of levels of C-peptide or other markers of metabolic control.     

Efficacy and Tolerability of Fixed-Dose Combination of Perindopril/Indapamide in Type 2 Diabetes Mellitus: PICASSO Trial

Background

Hypertension and type 2 diabetes mellitus (T2DM) synergistically deteriorate the vascular environment, making blood pressure reduction challenging, and substantially increasing cardiovascular risk.

Methods

In the real-life, open-label, observational, PICASSO study, 9,257 hypertensive patients unsuccessfully treated with antihypertensives were switched to fixed-dose combination of perindopril 10 mg/indapamide 2.5 mg. In this subgroup analysis, we analyzed changes in blood pressure and laboratory parameters of 2,762 hypertensive patients with T2DM or pre-diabetes.

Results

After 3 months of treatment, significant decreases in office blood pressure were noted in the whole cohort (?27.0 ± 14.8/?12.7 ± 9.8 mmHg; p < 0.001). Significant decreases were also recorded in patients with grade 1 hypertension (19.2 ± 10.0/?9.4 ± 7.9 mmHg), grade 2 (29.2 ± 10.9/?13.3 ± 8.7 mmHg) and grade 3 (?45.1 ± 15.4/?21.5 ± 11.2 mmHg). Significant decreases in ambulatory blood pressure were also noted (n = 93). In patients previously treated with angiotensin-converting enzyme inhibitor ± hydrochlorothiazide or angiotensin receptor blocker ± hydrochlorothiazide, mean 24-h blood pressure decreased by 23.4 ± 13.9/11.5 ± 9.7 and 22.3 ± 8.7/10.4 ± 13.2 mmHg, respectively (p < 0.001). Treatment was well tolerated and the switch to treatment with perindopril/indapamide was associated with improvements in laboratory parameters.

Conclusions

Data from this diabetes subgroup analysis suggest that fixed combination of perindopril 10 mg/indapamide 2.5 mg should be routinely considered for the treatment of hypertension in diabetic patients who are unsuccessfully managed with other antihypertensive medications.     

多药联用综合治疗高血压合并糖尿病的临床疗效研究

[目的]探讨多药联合综合治疗高血压合并糖尿病的临床疗效.[方法]选取2015年6月至2016年6月本院收治的高血压合并糖尿病的患者94例,应用随机数字表法分为观察组与对照组,对照组患者给予常规降压药物治疗,治疗组患者采用多药联用综合治疗,对比两组患者的临床疗效,并对比治疗前后两组患者的收缩压(SBP)、舒张压(DBP)、空腹血糖(FPG)、血尿素氮(BUN)、血清肌酐(SCr)、血清钾(K+)及尿酸(UA)等变化.[结果]与对照组对比,观察组患者的总有效率为93.62％显著高于对照组的85.11％,差异有统计学意义(x2 =8.732,P＜0.05);与治疗前对比,治疗后两组患者的SBP、DBP及FPG水平均明显改善,且观察组患者的SBP、DBP及FPG水平较对照组患者改善更明显(P＜0.05);与治疗前对比,治疗后观察组患者的BUN及SCr均显著改善(P＜0.05),但UA及K+水平无显著改善,且两组比较无显著差异(P＞0.05).[结论]多药联合综合治疗高血压合并糖尿病疗效显著,可有效控制患者病情,值得临床推广.     

两种胰岛素强化治疗方案治疗2型糖尿病疗效观察分析

目的观察采用胰岛素泵持续皮下输注胰岛素(CSII)和采用胰岛素泵多次皮下注射胰岛素(MSII)两种治疗方案对2型糖尿病的疗效。方法对68例2型糖尿病患者分别采取胰岛素泵持续皮下输注胰岛素法(CSII)(34例),和采用胰岛素泵多次皮下注射胰岛素法(MSII)(34例),比较二者达到标准血糖值的时间先后及血糖控制程度。结果采用胰岛素泵持续皮下输注胰岛素(CSII)较采用胰岛素泵多次皮下注射胰岛素(MSII)用时更短,对胰岛素量的需求也更少。结论临床实践中,在治疗2型糖尿病时,要尽可能使用胰岛素泵持续皮下输注胰岛素法(CSII)。     

The Role of Adjunctive Exenatide Therapy in Pediatric Type 1 Diabetes

OBJECTIVE

Exenatide improves postprandial glycemic excursions in type 2 diabetes. Exenatide could benefit type 1 diabetes as well. We aimed to determine an effective and safe glucose-lowering adjuvant exenatide dose in adolescents with type 1 diabetes.

RESEARCH DESIGN AND METHODS

Eight subjects completed a three-part double-blinded randomized controlled study of premeal exenatide. Two doses of exenatide (1.25 and 2.5 μg) were compared with insulin monotherapy. Prandial insulin dose was reduced by 20%. Gastric emptying and hormones were analyzed for 300 min postmeal.

RESULTS

Treatment with both doses of exenatide versus insulin monotherapy significantly reduced glucose excursions over 300 min (P < 0.0001). Exenatide administration failed to suppress glucagon but delayed gastric emptying (P < 0.004).

CONCLUSIONS

Adjunctive exenatide therapy reduces postprandial hyperglycemia in adolescents with type 1 diabetes. This reduction in glucose excursion occurs despite reduction in insulin dose. We suggest that exenatide has therapeutic potential as adjunctive therapy in type 1 diabetes.Intensive insulin therapy delays/prevents complications associated with type 1 diabetes (1,2). However, insulin monotherapy fails to achieve normoglycemia (3). Postprandial hyperglycemia and hypoglycemia (4,5) continue to create impediments to management. Even the closed-loop system fails to normalize postprandial hyperglycemia (6). Additional therapies to insulin are needed to achieve optimal glycemic control.Glucagon-like peptide (GLP)-1 is an incretin secreted in response to nutrient ingestion (7). Physiological GLP-1 enhances insulin secretion, delays gastric emptying, and suppresses glucagon. But because of its short half-life (8), it is unsuitable for clinical application.Exenatide is a long-acting GLP-1 receptor agonist and acts similarly to native GLP-1 (9). Exenatide is effective in decreasing postprandial hyperglycemia in type 2 diabetes (10). However, there are few studies using exenatide in type 1 diabetes and none in adolescents. The objective of our study was to examine the effect of adjuvant premeal exenatide and insulin on postprandial glucose in type 1 diabetes and establish an effective and safe glucose-lowering dose.     

综合疗法治疗儿童弱视疗效分析

目的观察探讨综合疗法对儿童弱视的临床疗效。方法以我院门诊治疗的弱视患者186例(263眼)为研究对象,对所有患者采用综合疗法治疗,包括遮盖法、增视训练、精细目力训练及药物治疗。分析不同弱视类型、不同弱视程度、不同患者年龄及不同注视类型间的基本治愈率差异。结果弱视治疗的总有效率为91.63%,其中治愈率为75.67%,进步为15.97%,无效为8.37%,治愈疗程平均为6个月。弱视的治疗效果与弱视类型、弱视程度、患者年龄及注视类型等密切相关,弱视程度越轻、患者年龄越小的屈光不正性及中心注视性弱视的基本治愈率更高。结论弱视的治疗效果与弱视类型、弱视程度、患者年龄及注视类型等密切相关,综合疗法可以提高弱视治愈率,缩短治疗时间。     

维格列汀与二甲双胍联合治疗对2型糖尿病患者IL-6、TNF-a、CRP的影响

目的探讨维格列汀与二甲双胍联合治疗对2型糖尿病患者白细胞介素6(IL-6)、肿瘤坏死因子a(TNF-a)、C反应蛋白(CRP)的影响。方法将104例2型糖尿病患者平均分为研究组与对照组。对照组给予盐酸二甲双胍治疗,研究组在对照组的基础上联合维格列汀治疗。结果两组血糖指标(FPG、Hb A1c、2h PG)明显降低(P0.05);且研究组FPG、Hb A1c水平低于对照组(P0.05)。研究组IL-6、TNF-a、CRP水平明显低于对照组及治疗前(P0.05)。结论针对2型糖尿病患者采取维格列汀与二甲双胍联合治疗,可以有效改善血糖水平,延缓糖尿病病情进展,降低合并症及并发症的发生率,安全可靠,适于推广。     

Detection of GAD65-reactive T-Cells in type 1 diabetes by immunoglobulin-free ELISPOT assays

OBJECTIVE: To investigate the prevalence of beta-cell autoantigen-reactive peripheral T-cells in type 1 diabetes, we developed an immunoglobulin-free enzyme-linked immunospot (ELISPOT) assay and assessed its usefulness for diagnosing this disease. RESEARCH DESIGN AND METHODS: Cellular immune responses to beta -cell autoantigens were studied both by immunoglobulin-free proliferation assays and ELISPOT assays in 33 patients with type 1 diabetes and 15 patients with type 2 diabetes, compared with 23 healthy control subjects. Autoantibodies against GAD65 and IA-2 were measured by radioimmunoassay. RESULTS: Significant proliferative responses to GAD65 were observed in 10 of 31 (32.3%) type 1 diabetic patients (P < 0.05), whereas GAD65-reactive gamma-interferon (IFN-gamma)-secreting cells were detected in 22 of 33 patients (66.7%) by ELISPOT assay (P < 0.001). Of patients negative for both GAD65 and IA-2, five of six (83.3%) showed IFN-gamma positivity in ELISPOT and two of five (40.0%) showed significant proliferation against GAD65. CONCLUSIONS: Using a newly developed ELISPOT assay, GAD-reactive T-helper 1 cells in PBMC of type 1 diabetic patients could be identified at a higher frequency than by the proliferation assay. Therefore, the immunoglobulin-free ELISPOT assay is an excellent tool for detecting T-cell reactivity to autoantigens with greater specificity and, in combination with beta-cell autoantibody determination, will improve the diagnosis of type 1 diabetes.     

罗格列酮与胰岛素联合治疗2型糖尿病的疗效观察

目的:探讨胰岛素联合罗格列酮治疗2型DM的协同作用、安全性。方法:将21例2型DM患者采用随机法分为两组,两组用药前FPG、PPG及每日胰岛素用量均无统计学差异。A组11例使用基因合成人胰岛素三短一中方案治疗12周。B组10例使用基因合成人胰岛素三短一中及联合罗格列酮治疗方案12周。结果:治疗12周后,两组的FPG及2hPPG均有所降低,以B组下降更为明显,有显著差异(P<0.001),用药后,B组的TG有明显改善,胰岛素用量也明显减少(P<0.001),HDL-C及舒张压也有所改善(P<0.05),而两组治疗前后BUN、Cr、TB、ALT均无统计学差异。结论:在2型DM治疗中,胰岛素联合罗格列酮方案能使2型DM患者的血糖得到很好控制,并可减少其胰岛素用量,有很好的协同作用和安全性,无明显不良事件发生。     

Open-Label Study Assessing the Long-term Efficacy and Safety of Triple Olmesartan/Amlodipine/Hydrochlorothiazide Combination Therapy for Hypertension

Introduction

To reduce cardiovascular risk associated with hypertension, the majority of patients require at least two drugs to control their blood pressure (BP), and many require three or more.

Methods

An open-label extension of a 10-week double-blind study assessed the long-term efficacy and safety of olmesartan/amlodipine/hydrochlorothiazide (OLM/AML/HCTZ) triple combination treatment in 2,509 patients with Grade 2–3 hypertension. After 8 weeks of single-blind OLM/AML/HCTZ 20/5/12.5 mg treatment, patients at BP goal [seated systolic/diastolic BP (SeSBP/SeDBP) <140/90 mmHg, or <130/80 mmHg for patients with diabetes, or chronic kidney or cardiovascular disease] entered open-label treatment for 36 weeks. Patients not at goal received 8 weeks of randomized, double-blind treatment before entering open-label treatment. During open-label treatment, patients received OLM/AML/HCTZ 20/5/12.5, 40/5/12.5, 40/5/25, 40/10/12.5 or 40/10/25 mg with up- or down-titration as needed to achieve BP goals.

Results

During open-label treatment, mean SeSBP/SeDBP levels remained within the ranges 120–140 and 75–85 mmHg, respectively. At study end, significant reductions from baseline were seen in each group for SeSBP (37–43 mmHg) and SeDBP (22–27 mmHg), and 78.1% of patients overall achieved BP goal. Categorical analysis of patients by baseline SeSBP (150–159, 160–169, 170–179, 180–189, 190 to <200 mmHg) correlated with changes in SeSBP. Patients in the lowest baseline category (150–159 mmHg) showed a reduction of 34.3 mmHg, and those in the highest category (190 to <200 mmHg) showed a 59.4 mmHg reduction. At baseline, 90.8% of patients had Grade 2 or 3 hypertension, but at study end 91.9% had normal/high-normal BP. The incidence of adverse events was similar across the treatment groups.

Conclusion

In patients with Grade 2–3 hypertension, long-term treatment with OLM/AML/HCTZ triple combination therapy was well tolerated and effective. A high level of BP control and a substantial reduction in the level of hypertension severity were achieved.     

多镜联合治疗复杂性肾结石的疗效观察

【目的】探讨多镜联合治疗复杂性肾结石的疗效。【方法】多镜联合治疗复杂性肾结石61例,选择输尿管硬镜联合组合式输尿管软镜碎石35例;单通道经皮肾镜联合组合式输尿管软镜碎石26例。【结果】输尿管硬镜联合组合式输尿管软镜碎石35例结石患者中,碎石成功率97．14％（34/35）,结石清除率为83．86％（29/35）。碎石手术时间50～100 min。术后住院2～7 d;单通道经皮肾镜联合组合式输尿管软镜碎石26例患者全部肾盂及主要肾盏结石均顺利击碎并排出,一期清除率为80．77％（21/26）,总结石清除率为92．30％（24/26）。碎石手术时间50～140 min。肾造瘘管留置时间5～35 d ,术后住院6～10 d。【结论】多镜联合治疗复杂性肾结石,可提高复杂性肾结石的结石清除率,减小手术创伤,缩短手术时间,降低手术风险及并发症,是复杂性肾结石较好的治疗方法。     

2型糖尿病焦虑、抑郁调查及对糖尿病治疗效果的影响

【目的】探讨2型糖尿病（T2DM）患者焦虑和抑郁的发生率及其对糖尿病治疗效果的影响。【方法】对86名T2DM患者和40名正常对照组进行心理学量表调查焦虑、抑郁,同时查血脂、血糖、HbA1c等指标,并观察血糖达标时间探讨对糖尿病治疗效果的影响。【结果】T2DM组40．1％存在抑郁,11．6％存在焦虑。合并抑郁、焦虑的T2DM患者对治疗有影响。【结论】T2DM的抑郁、焦虑发病率高,影响糖尿病的治疗。     

Effects of Naltrexone Sustained- Release/Bupropion Sustained-Release Combination Therapy on Body Weight and Glycemic Parameters in Overweight and Obese Patients With Type 2 Diabetes

OBJECTIVE

To assess the efficacy and safety of 32 mg naltrexone sustained-release (SR)/360 mg bupropion SR (NB) in overweight/obese individuals with type 2 diabetes with or without background oral antidiabetes drugs.

RESEARCH DESIGN AND METHODS

This was a 56-week, double-blind, placebo-controlled study in which 505 patients received standardized lifestyle intervention and were randomized 2:1 to NB or placebo. Coprimary end points were percent weight change and achievement of ≥5% weight loss. Secondary end points included achievement of HbA_1c <7% (53 mmol/mol), achievement of weight loss ≥10%, and change in HbA_1c, waist circumference, fasting blood glucose, and lipids.

RESULTS

In the modified intent-to-treat population (54% female, 80% Caucasian, and mean age 54 years, weight 106 kg, BMI 37 kg/m², and HbA_1c 8.0% [64 mmol/mol]), NB resulted in significantly greater weight reduction (−5.0 vs. −1.8%; P < 0.001) and proportion of patients achieving ≥5% weight loss (44.5 vs. 18.9%, P < 0.001) compared with placebo. NB also resulted in significantly greater HbA_1c reduction (−0.6 vs. −0.1% [6.6 vs. 1.1 mmol/mol]; P < 0.001), percent of patients achieving HbA_1c <7% (53 mmol/mol) (44.1 vs. 26.3%; P < 0.001), and improvement in triglycerides and HDL cholesterol compared with placebo. NB was associated with higher incidence of nausea (42.3 vs. 7.1%), constipation (17.7 vs. 7.1%), and vomiting (18.3 vs. 3.6%). No difference was observed between groups in the incidence of depression, suicidal ideation, or hypoglycemia.

CONCLUSIONS

NB therapy in overweight/obese patients with type 2 diabetes induced weight loss, which was associated with improvements in glycemic control and select cardiovascular risk factors and was generally well tolerated with a safety profile similar to that in patients without diabetes.Type 2 diabetes is a chronic disease characterized by elevated blood glucose and is often associated with a collection of metabolic abnormalities including low HDL cholesterol (HDL-C), elevated triglyceride concentrations, and high blood pressure. Excess body weight, particularly visceral adiposity, may contribute to the development of both diabetes and the associated metabolic abnormalities, perhaps due to pathologic effects of excessive adipose tissue (1). Based on the National Health and Nutrition Examination Survey (NHANES) data from 1999–2010, the combined prevalence of overweight and obesity in the U.S. is 69% (2), while the prevalence of overweight and obesity in people with type 2 diabetes has been estimated to be even higher at ~85% (3). Survey and clinical trial evidence supports a strong association between obesity (characterized by a BMI ≥30 kg/m² and central adiposity) and the development of insulin resistance, prediabetes, and type 2 diabetes (4).In patients with type 2 diabetes, the best achievable glycemic control for the individual is recommended to reduce the risk of microvascular and possibly macrovascular disease. While lifestyle modifications can improve glycemic control, most patients with type 2 diabetes will typically require the sequential addition of one or more medications to achieve and sustain glycemic control. Unfortunately, many glucose-lowering medications lead to an increase in body weight (5). This presents challenges in an overweight or obese patient population often already struggling with weight control, particularly given that even modest intentional weight loss can improve cardiovascular risk factors (6,7) and decrease mortality (8).Bupropion is a dopamine and norepinephrine reuptake inhibitor approved for use in the U.S. as an antidepressant and smoking cessation agent (9,10), with variable and modest effects on body weight as monotherapy (11). Naltrexone is an opioid receptor antagonist approved for use in the management of alcohol and opioid dependence (12). Animal studies suggest that when used together, bupropion and naltrexone increase the firing rate of proopiomelancortin neurons, in part due to naltrexone-induced reduction of an autoinhibitory effect of β-endorphins (13). Increased proopiomelancortin neuronal firing increases secretion of melanocortins such as α-melanocyte stimulating hormone, which is thought to mediate anorectic effects and regulate energy balance (14). Furthermore, naltrexone and bupropion therapy are believed to influence the mesolimbic dopaminergic reward system, which can modulate reward behaviors such as food intake (14,15). Thus, this novel combination treatment is believed to act on the central nervous system to elicit sustained appetite reduction and enhance control of eating behavior.While the development and clinical use of bupropion and naltrexone have spanned more than two decades, only recently have studies investigated the combined use of these agents in sustained-release (SR) form as a potential therapy for obesity. All three phase 3 trials of naltrexone SR plus bupropion SR (NB) in overweight or obese patients without diabetes demonstrated significant weight loss with an acceptable safety profile (16–18). This report details a 56-week, double-blind, placebo-controlled phase 3 clinical trial of NB for the treatment of overweight or obese patients with type 2 diabetes.     

鼻部联合治疗儿童急性分泌性中耳炎的疗效分析

目的:观察鼻部联合治疗儿童急性分泌性中耳炎的临床疗效。方法:2010年5月—2011年12月收治100例(126耳)急性分泌性中耳炎的儿童,随机分为鼻部联合治疗组(治疗组,60例,76耳)和对照组(40例,50耳),两组同时给予常规全身药物治疗。分别于第7天和第14天复诊,比较两组的治疗效果。结果:治疗组有效72耳,无效4耳,总有效率94.7%;对照组有效35耳,无效15耳,总有效率70%;两组差异有统计学意义(P<0.05)。结论:鼻部联合治疗儿童急性分泌性中耳炎效果较好。     

The Efficacy and Safety of Imeglimin as Add-on Therapy in Patients With Type 2 Diabetes Inadequately Controlled With Metformin Monotherapy

OBJECTIVE

A 12-week study assessed the efficacy and safety of a new oral antidiabetic agent, imeglimin, as add-on therapy in type 2 diabetes patients inadequately controlled with metformin alone.

RESEARCH DESIGN AND METHODS

A total of 156 patients were randomized 1:1 to receive imeglimin (1,500 mg twice a day) or placebo added to a stable dose of metformin (1,500–2,000 mg/day). Change in A1C from baseline was the primary efficacy outcome; secondary outcomes included fasting plasma glucose (FPG) and proinsulin/insulin ratio.

RESULTS

After 12 weeks, the placebo-subtracted decrease in A1C with metformin-imeglimin was −0.44% (P < 0.001). Metformin-imeglimin also significantly improved FPG and the proinsulin/insulin ratio from baseline (−0.91 mg/dL and −7.5, respectively) compared with metformin-placebo (0.36 mg/dL and 11.81). Metformin-imeglimin therapy was generally well-tolerated with a comparable safety profile to metformin-placebo.

CONCLUSIONS

Addition of imeglimin to metformin improved glycemic control and offers potential as a new treatment for type 2 diabetes.Imeglimin is the first in a new tetrahydrotriazine-containing class of oral antidiabetic agents, the glimins. Imeglimin decreases hepatic glucose production, increases muscle glucose uptake, and improves pancreatic glucose-dependent insulin secretion (1).Previous studies have demonstrated imeglimin to be as effective as metformin in improving glycemia (2). Since metformin is the preferred first-line therapy for type 2 diabetes, the current study examined the efficacy, safety, and tolerability of imeglimin in combination with metformin in patients with type 2 diabetes inadequately controlled with metformin alone.     

罗格列酮治疗30例2型糖尿病的临床疗效

目的 :观察罗格列酮联合治疗 2型糖尿病的疗效和安全性。方法 :6 0例 2型糖尿病患者分为 2组 ,罗格列酮组 (30例 )在原治疗方案基础上联合罗格列酮 4mg,qd ,po ,对照组 (30例 )维持原治疗方案。试验历时 5 2周 ,观察空腹血糖、糖化血红蛋白 (HbA1c)、空腹胰岛素、稳态模式胰岛素抵抗指数 (HOMA -IR)和血脂的变化。结果 :罗格列酮组空腹血糖、HbA1c、空腹胰岛素和HOMA -IR治疗后较治疗前明显下降 ,分别下降了 (1.4± 1.3)mmol·L-1,(0 .8± 1.0 ) % ,(3± 6 )mU·L-1和 (1.93± 3.13) ,均P <0 .0 5 ,而对照组治疗前后的变化无显著差异 (P >0 .0 5 ) ,2组间存在显著差异 (P <0 .0 5 ) ,罗格列酮组的高密度脂蛋白 (HDL -ch)、HDL -ch总胆固醇变化水平明显高于对照组 (分别为P <0 .0 1和P <0 .0 5 )。结论 :罗格列酮可降低 2型糖尿病患者的胰岛素水平 ,改善胰岛素抵抗 ,长期、有效地控制血糖 ,并能改善脂代谢 ,减少心血管疾病的危险因素 ,安全性好