Pioglitazone as monotherapy or in combination with sulfonylurea or metformin enhances insulin sensitivity (HOMA-S or QUICKI) in patients with type 2 diabetes

BACKGROUND: Miyazaki et al. demonstrated using the hyperinsulinemic, euglycemic clamp that pioglitazone (PIO) enhanced insulin sensitivity in patients (n = 23) with type 2 diabetes (T2D). Although considered the reference method for measuring insulin sensitivity, the clamp is seldom used in large clinical trials because of its complexity.The Homeostasis Model Assessment Insulin Sensitivity (HOMA-S) and Quantitative Insulin Sensitivity Check Index (QUICKI) are two alternative insulin sensitivity surrogates that correlate with the clamp method and are suitable for use with large study populations. STUDY AIM: To evaluate the effect of PIO monotherapy and in combination therapy with sulfonylurea (SU) or metformin (MET) on insulin sensitivity as assessed by HOMA-S and QUICKI in a large group of patients (approximately 1000). Research design and methods: Patient data from three randomized, double blind, multicenter, parallel group, placebo-controlled registration trials (Studies-001 PIO monotherapy and 010 and 027 combination therapy with SU or MET, respectively) were analyzed for this study.We evaluated insulin sensitivity for all three studies using HOMA-S and QUICKI. RESULTS: PIO 15, 30 and 45 mg enhanced HOMA-S compared with baseline (56.9-63.6%, p = 0.0298); (53.7-64.7%, p = 0.0008); (59.0-75.9%, p < 0.0001), respectively. Only the 45 mg dose showed a difference from placebo (p = 0.0025). Similarly, PIO enhanced QUICKI versus baseline (0.290-0.296, p = 0.0026); (0.287-0.299, p = 0.0001); (0.290-0.306, p = 0.0001), respectively. Both the 30 and 45 mg doses were different from placebo for QUICKI (p = 0.0005, p < 0.0001). PIO 15 and 30 mg plus SU enhanced HOMA-S compared with baseline (58.4-66.7%, p = 0.0007; 53.2-68.4%, p < 0.0001) and placebo plus SU (p = 0.0129, p < 0.0001, respectively). Likewise, PIO 15 and 30 mg plus SU enhanced QUICKI versus baseline (0.289-0.300, p = 0.0001; 0.287-0.305, p = 0.0001, respectively). Both doses had different effects from placebo plus SU (p = 0.0001) for QUICKI. PIO 30mg combined with MET enhanced HOMA-S versus baseline (66.2-82.2%, p < 0.0001) and placebo plus MET (p = 0.0002). Similarly, PIO 30 mg plus MET enhanced QUICKI compared with baseline (0.295-0.309, p = 0.0001) and placebo plus MET (p = 0.0001). CONCLUSION: PIO monotherapy and combination therapy with SU or MET enhanced insulin sensitivity as evaluated by HOMA-S and QUICKI. Both measures can detect changes in sensitivity for large numbers of subjects when the reference method hyperinsulinemic euglycemic clamp, or other complex methods are not feasible.     

Efficacy and safety of pioglitazone/metformin fixed-dose combination therapy compared with pioglitazone and metformin monotherapy in treating patients with T2DM

Abstract

Background:

Studies have shown that many patients with type 2 diabetes do not achieve optimal glycemic control, and progression of diabetes over time requires more than one pharmacotherapy to achieve glycemic goal.     

Effect of saxagliptin as add-on therapy in patients with poorly controlled type 2 diabetes on insulin alone or insulin combined with metformin

Abstract

Objective:

To evaluate efficacy and safety of saxagliptin as add-on therapy in patients with type 2 diabetes (T2D) with inadequate glycemic control on insulin alone or combined with metformin.     

吡格列酮联合二甲双胍治疗2型糖尿病疗效观察

目的观察吡格列酮联合二甲双胍治疗2型糖尿病的临床疗效。方法152例2型糖尿病患者按数字表法随机分为对照组和治疗组各76例,对照组口服二甲双胍0．5g,3次／d;治疗组给予吡格列酮30mg,1次／d,同时口服二甲双胍0．5g,3次／d。两组连续治疗3个月。结果治疗组治疗总有效率96．1％明显高于对照组的84．2％（P〈0．05）;两组治疗后空腹血糖和餐后血糖均明显低于治疗前（均P〈0．05）,治疗组较对照组降低更明显（均P〈0．05）;两组均未发生严重不良反应。结论吡格列酮联合二甲双胍治疗2型糖尿病临床效果显著,优于单用二甲双胍治疗。     

Effects of early use of pioglitazone in combination with metformin in patients with newly diagnosed type 2 diabetes

ABSTRACT

Background: Type 2 diabetes is characterised by a progressive decline in HbA_1c control over time. Early combination therapy, rather than sequential introduction of individual oral glucose-lowering agents, has been proposed to prevent this gradual rise in HbA_1c. This observational study assessed the effect of early dual combination oral glucose-lowering therapies within 6 months of diagnosis in newly diagnosed, drug-naïve patients with type 2 diabetes.

Patients and methods: This was an observational, open-label, non-randomised study in newly diagnosed patients with type 2 diabetes, aged 35–70 years, with HbA_1c levels >?8.0% at diagnosis or >?7.0% at the 3–6-month follow-up. Patients were allocated to dietary management alone if the HbA_1c level was 7.0–8.0% at diagnosis. Metformin combined with gliclazide, repaglinide, or pioglitazone was given at diagnosis if the HbA_1c was >?8.0%. Similar treatments were introduced at 3–6 months if the HbA_1c was >?7.0%. Over a 3-year period, HbA_1c was measured at 3-monthly intervals. All patients underwent regular dietetic review. Target HbA_1c was ≤?7.0%.

Results: 416 patients were considered eligible for inclusion, with a mean (±?SD) age of 54.1 ± 9.2 years, BMI of 33.5 ± 6.1?kg/m², and baseline HbA_1c of 8.6 ± 1.7%. A mixed model analysis of variance on the 178 patients who started with combination therapy, either immediately or after a 3–6 month period on diet, showed that metformin plus gliclazide, repaglinide, or pioglitazone was associated with a gradual increase in HbA_1c values. Amongst those patients treated with the metformin/pio­glitazone combination there was an estimated 0.1% increase in HbA_1c/year. This was much less pronounced than the rises seen in HbA_1c/year of 0.5% with the met­formin/gliclazide and metformin/repaglinide combinations.

Conclusions: This preliminary analysis of an obervational, non-randomised, open-label ongoing study has shown that early use of combination therapy at time of diagnosis or within the first 3–6 months following diagnosis with metformin plus pioglitazone in newly diagnosed type 2 diabetes results in a slower deterioration in glycaemic control than that with metformin combined with either gliclazide or repaglinide. This may be due to the β?cell protective properties of pioglitazone. These results need to be confirmed by further studies with a more robust design and methodology.     

二甲双胍和吡格列酮对2型糖尿病患者的疗效及抗氧化作用研究

目的 探讨二甲双胍或吡格列酮对2型糖尿病患者的疗效及其对超氧化物歧化酶（SOD）、丙二醛（MDA）的影响。方法 纳入北京市昌平区中西医结合医院收治的2型糖尿病患者160例,按随机数字表法平均分为二甲双胍组和吡格列酮组,分别给予盐酸二甲双胍肠溶片（1 g/次,每日2次）和盐酸吡格列酮片（30 mg/次,每日1次）,两组疗程均为4周。比较两组患者治疗前后空腹血糖（FPG）、餐后2 h血糖（PPPG）、糖化血红蛋白（HbA1c）,血脂以及两组患者SOD、MDA水平。结果 给予降糖药4周后,两组患者FPG、PPPG、HbA1c均显著下降,同组治疗前后比较差异有统计学意义（P<0.05）。治疗后,二甲双胍组患者三酰甘油（TG）、低密度脂蛋白（LDL）水平显著降低,同组治疗前后比较差异有统计学意义（P<0.05）,而吡格列酮患者则无显著性变化。吡格列酮组患者血清MDA水平下降,同组治疗前后比较差异有统计学意义（P<0.05）;二甲双胍组患者血清SOD水平显著上升（P<0.05）,且显著高于吡格列酮组（P<0.05）;吡格列酮组患者血清MDA水平显著下降（P<0.05）,且显著低于二甲双胍组（P<0.05）。结论 二甲双胍或吡格列酮均能改善胰岛素抵抗和糖尿病并发症;吡格列酮降低MDA水平效果优于二甲双胍,但增加SOD水平仅见于二甲双胍。两种药物对氧化应激的作用机制不同,有利于联合用药。     

二甲双胍联合西格列汀或吡格列酮对肥胖型2型糖尿病的疗效比较

目的：比较西格列汀与吡格列酮分别联用二甲双胍治疗二甲双胍单药控制不佳的肥胖型2型糖尿病的疗效。方法：60例2型糖尿病肥胖患者在服用二甲双胍片的前提下,随机分为西格列汀组（n=30）和吡格列酮组（n=30）,分别给予西格列汀片与吡格列酮片口服,检测入组时和治疗12周后两组糖化血红蛋白、空腹及餐后血糖水平、低血糖例数、体重指数等数据。结果：治疗12周后,西格列汀组患者的糖化血红蛋白、空腹及餐后血糖、体重指数均比吡格列酮组改善明显,两组均无低血糖发生。结论：西格列汀联用二甲双胍片治疗肥胖型2型糖尿病的疗效优于吡格列酮片联用二甲双胍片。     

吡格列酮联合二甲双胍对2型糖尿病周围神经病变患者血尿酸变化的影响

目的 探讨吡格列酮对2型糖尿病周围神经病变患者血尿酸变化的影响。方法 收集2014年7月-2015年7月在南通市通州区第三人民医院住院并确诊患有糖尿病周围神经病变的患者80例,随机分为对照组和观察组各40例,两组患者均进行饮食控制结合运动疗法等一般治疗方式。对照组给予二甲双胍治疗,0.5 g/次,每日3次。观察组在对照组的基础上给予吡格列酮治疗,吡格列酮剂量为15 mg/次,每日1次。两组服药时间均为2个月。结果 两组空腹血糖及餐后2 h血糖浓度经治疗后均降低,观察组低于对照组（P<0.05）;对照组治疗前后血尿酸差异无明显变化（P>0.05）,观察组治疗后血尿酸浓度显著降低（P<0.05）;两组治疗后CSS评分均低于治疗前评分（P<0.05）;治疗后观察组评分低于对照组（P<0.05）。结论 吡格列酮联合二甲双胍对治疗2型糖尿病周围神经病变有一定疗效,可降低2型糖尿病周围神经病变患者血尿酸水平。     

门冬胰岛素联合吡格列酮二甲双胍治疗糖尿病患者的临床效果及安全性

目的 探究门冬胰岛素联合吡格列酮二甲双胍治疗糖尿病患者的临床效果及安全性。方法 90例糖尿病患者,采取随机数字表法分为观察组与对照组,各45例。对照组给予门冬胰岛素30治疗,观察组在对照组基础上加用吡格列酮二甲双胍治疗。对比两组治疗前后的血糖相关指标、胰岛素用量、不良反应发生率。结果 治疗后,观察组空腹血糖(5.66±1.09)mmol/L、餐后2 h血糖(9.80±1.97)mmol/L、糖化血红蛋白(6.40±1.15)%均低于对照组的(8.57±1.25)mmol/L、(15.43±3.09)mmol/L、(7.85±1.27)%,差异有统计学意义(P<0.05)。观察组治疗期间胰岛素用量(32.78±5.50)U少于对照组的(41.08±6.33)U,差异有统计学意义(P<0.05)。两组不良反应发生率比较,差异无统计学意义(P>0.05)。结论 门冬胰岛素联合吡格列酮二甲双胍治疗糖尿病患者可取得较好的降低血糖水平的目的 ,安全性高。     

吡格列酮联合胰岛素对2型糖尿病患者脂联素水平的影响

目的观察吡格列酮联合胰岛素治疗2型糖尿病对患者血浆脂联素水平的影响。方法60例2型糖尿病患者随机分为2组,分别给予胰岛素及吡格列酮联合胰岛素治疗,疗程共12周。分别检测和记录2组患者治疗前后空腹血糖(FBG)、糖化血红蛋白(HbA1c)、脂联素以及胰岛素用量,观察吡格列酮对2型糖尿病患者血浆脂联素的影响。结果2组患者治疗后血糖和HbA1c均控制良好,其中观察组胰岛素日需求量明显低于对照组(P<0.05);观察组血浆脂联素水平较对照组明显升高(P<0.05)。结论吡格列酮联合胰岛素治疗2型糖尿病不仅可良好地控制血糖HbA1c,同时增加患者血浆脂联素水平,提高患者对胰岛素的敏感性,减少胰岛素用量。     

2型糖尿病患者血清脂联素和胰岛素敏感性的相关性

目的探讨正常人和2型糖尿病（T2DM）患者血清脂联素（APN）和胰岛素敏感性的相关性。方法正常对照组20例,T2DM58例按体重指数（BMI）又分为正常体重组（16例）、超重组（22例）和肥胖组（20例）。测定正常对照组和T2DM各组患者的胰岛素抵抗指数（HOMA-IR）、APN、糖化血红蛋白（HbA1C）、空腹血糖（FPG）和空腹胰岛素（FINS）水平。结果与正常对照组相比,T2DM超重组和肥胖组的APN显著降低（均P〈0．01）,肥胖组APN较超重组显著降低,超重组APN较正常体重组显著降低（均P〈0．05）;与正常对照组相比,T2DM各组HOMA-IR显著升高（均P〈0．01）。所有研究个体APN与BMI（r=-0．538,P〈0．01）和HOMA-IR（r=-0．459,P〈0．01）呈显著负相关。结论T2DM患者血清APN水平显著降低,并以超重组和肥胖组患者降低更为明显;APN与HOMA-IR和BMI呈显著负相关。     

胰岛素联合二甲双胍或优降糖治疗2型糖尿病的疗效比较

目的探讨胰岛素联合二甲双胍或优降糖对单一磺酰脲类药物治疗失效的2型糖尿病的临床疗效。方法80例患者随机分为2组，均采用胰岛素治疗，一组加服二甲双胍，一组加服优降糖，观察治疗12周前后空腹血糖（FPG）、餐后2小时血糖（2hPG）、糖化血红蛋白（HbA1C）、体重指数（BMI）、血甘油三酯（TG）、总胆固醇（TC）、低密度脂蛋白（LDL-C）及高密度脂蛋白（HDL-C）的变化。结果两组FPG、2hPG、HbA1C均较治疗前明显下降，优降糖组BMI增高明显，二甲双胍组TG、TC、LDL-C降低有统计学差异。结论2组均能很好控制血糖，但联合二甲双胍在纠正血脂紊乱，避免体重增加等不良反应方面较联合优降糖更佳。     

The effect of vildagliptin relative to sulfonylurea as dual therapy with metformin (or as monotherapy) in Muslim patients with type 2 diabetes fasting during Ramadan in the Middle East: the VIRTUE study

Objective: To assess the effect of vildagliptin relative to sulfonylurea (SU) on hypoglycemic events, in Muslim patients from the Middle East with type 2 diabetes who fast during Ramadan. The primary endpoint was the proportion of patients with at least one hypoglycemic event (HE) during the fasting period. Secondary endpoints included change in weight, HbA1c levels, treatment adherence and overall safety.

Design and methods: This multicenter, prospective, observational cohort study enrolled Muslim adult T2DM patients from Middle Eastern countries who received treatment with vildagliptin or SU as add on to metformin or monotherapy. During a ～16 week observation period, data was collected up to 6 weeks before and 6 weeks after Ramadan fasting.

Results: A total of 584 patients from the Middle East enrolled in the study; 308 patients received vildagliptin and 265 received SU. Significantly fewer vildagliptin patients reported at least one HE (3.7% vildagliptin vs. 25.5% SU; p?p?=?.128). Mean change in HbA1c at the end of study showed ?0.18% between treatment difference in favor of vildagliptin, p?=?.001. Mean body weight change at the end of study showed ?0.68?kg between treatment difference in favor of vildagliptin, p?Limitations: Being observational and not mandating HE confirmation with blood glucose measurement (though it was done in a large number of patients) were key limitations.

Conclusion: Anti-hyperglycemic treatment with vildagliptin led to significantly fewer hypoglycemia events compared to sulfonylurea treatment among Muslim diabetic patients who fast during Ramadan. Good glycemic control, weight control and safety results supported this outcome.     

胰岛素联合口服药二甲双胍治疗2型糖尿病的临床体会

目的：探讨胰岛素联合口服药二甲双胍治疗2型糖尿病的临床效果。方法选取我院于2011年10月～2012年10月收治的2型糖尿病患者60例,随机分为观察组与对照组,各30例。对照组仅给予二甲双胍口服治疗,观察组给予胰岛素联合二甲双胍实施治疗,观察两组的治疗效果。结果治疗后,两组的血糖水平较治疗前均明显下降,且观察组的血糖水平明显优于对照组,P＜0.05;观察组的总有效率明显高于对照组（96.67% VS 70.00%）,不良反应发生率明显低于对照组（26.67% VS 73.33%）,差异有统计学意义（P＜0.05）。结论胰岛素联合口服药二甲双胍治疗2型糖尿病,疗效显著,不良反应少,值得临床推广。     

Achieving glycemic goal with initial versus sequential combination therapy using metformin and pioglitazone in type 2 diabetes mellitus

Abstract

Objective:

To compare glycemic goal achievement (HbA_1c?<?7%) in type 2 diabetes patients receiving initial metformin plus pioglitazone combination therapy and initial metformin monotherapy augmented with pioglitazone in a cohort follow-up study.     

甘精胰岛素联合二甲双胍治疗2型糖尿病的临床研究

目的探讨甘精胰岛素联合二甲双胍治疗2型糖尿病的临床疗效及安全性。方法将126例口服降糖药物血糖控制不理想的2型糖尿病患者随机分为对照组（60例）与观察组（66例）,对照组给予诺和灵N联合二甲双胍治疗,观察组给予甘精胰岛素联合二甲双胍治疗,疗程12周。比较两组患者血糖、血糖达标时间、糖化血红蛋白、胰岛功能及低血糖发生率。结果观察组血糖达标时间显著低于对照组（P〈0.05）;观察组餐后2 h血糖及糖化血红蛋白显著优于对照组（P〈0.05）;观察组餐后2 h C肽值显著高于对照组（P〈0.05）;观察组低血糖发生率显著低于对照组（22.7%vs.41.7%,P〈0.05）。结论与诺和灵N相比,甘精胰岛素联合二甲双胍降血糖效果更为理想,可改善胰岛功能,且安全性好。     

二甲双胍血糖控制不佳的2型糖尿病患者联合应用沙格列汀或吡格列酮疗效观察

目的 探讨二甲双胍血糖控制不佳的2型糖尿病患者联合沙格列汀或吡格列酮的疗效。方法 选择2015年1月至2016年1月安徽医科大第二附属医院内分泌门诊符合入选条件的2型糖尿病患者70例,随机被分为两组,观察组35例采用沙格列汀+二甲双胍治疗,对照组35例患者采用吡格列酮+二甲双胍治疗,观察两组治疗前后的空腹血糖（FPG）、餐后2 h血糖（2 hPG）、糖化血红蛋白（HbA1c）、空腹血清胰岛素水平、胰岛素抵抗指数（HOMA-IR）、体质指数（BMI）等。结果 与治疗前比较,治疗16周后观察组、对照组患者的FPG、餐后 2 hPG与HbA1c明显降低,HOMA-IR改善,差异有统计学意义（P<0.05）;但两组间差异无统计学意义（P>0.05）。与治疗前比较,治疗16周后观察组BMI无明显变化,差异无统计学意义（P>0.05）,对照组患者BMI明显上升,差异有统计学意义（P<0.05）,两组间差异有统计学意义（P<0.05）。结论 沙格列汀或吡格列酮联合二甲双胍可有效控制2型糖尿病患者血糖、改善胰岛素敏感性,沙格列汀不增加体质量且不良反应小,联合二甲双胍治疗是一种安全可靠的治疗方法。     

甘精胰岛素联合盐酸二甲双胍治疗2型糖尿病疗效观察

目的探讨甘精胰岛素联合盐酸二甲双胍治疗2型糖尿病的临床效果。方法选择本院2型糖尿病患者80例,将上述患者随机分为观察组和对照组。两组均给予糖尿病相关健康教育,控制饮食和适当运动。两组均给予二甲双胍．对照组给予诺和灵N,观察组给予甘精胰岛素。记录两组患者血糖达标时间、每天所用胰岛素总量;观察两组低血糖反应发生情况。结果观察组血糖达标时间显著低于对照组,差异有统计学意义（P〈0．05）;观察组日胰岛素用量显著低于对照组,差异有统计学意义（P〈0．05）：观察组夜间低血糖发生率显著低于对照组,差异有统计学意义（P〈0．05）。结论甘精胰岛素联合盐酸二甲双胍治疗2型糖尿病疗效显著,能够较短时间控制皿糖,降低低血糖反应发生,临床效果显著。     

Exenatide: a review of its use in patients with type 2 diabetes mellitus (as an adjunct to metformin and/or a sulfonylurea)

Exenatide (Byetta) is a novel, synthetic, incretin mimetic, glucoregulatory peptide approved in the US and Europe for the treatment of patients with type 2 diabetes mellitus who have inadequate glycaemic control despite receiving treatment with maximum tolerated doses of metformin and/or a sulfonylurea. In randomised, controlled, phase III trials and post hoc completer analyses in this patient population, the addition of subcutaneous exenatide twice daily significantly improved glycaemic control and was associated with progressive and significant bodyweight reduction from baseline for up to 2 years. The overall intensity of glycaemic control with exenatide was similar to that achieved with once-daily insulin glargine or twice-daily biphasic insulin aspart. Exenatide was generally well tolerated. Most adverse events were mild to moderate in severity and gastrointestinal in nature. The overall rate of hypoglycaemia was similar to rates observed with placebo (when administered with metformin) and insulin comparators (when administered with metformin and a sulfonylurea). The addition of exenatide to therapy with metformin and a sulfonylurea provided significant improvements in treatment satisfaction and patients' health-related quality of life (HR-QOL). The drug was also cost effective compared with pioglitazone, glibenclamide (glyburide), insulin glargine (all in combination with metformin and/or a sulfonylurea) and metformin alone. Overall, adjunctive therapy with exenatide is a valuable therapeutic option in patients with type 2 diabetes requiring moderate improvements in glycaemic control despite treatment with metformin and/or a sulfonylurea.