Therapeutic efficacy of mitiglinide combined with once daily insulin glargine after switching from multiple daily insulin regimen of aspart insulin and glargine in patients with type 2 diabetes mellitus

Mitiglinide is novel class of rapid-acting insulin secretagogues, which have been widely used alone or in combination with other oral hypoglycemic drugs to improve postprandial hyperglycemia in early type 2 diabetes. While mitiglinide enhances postprandial requirement of insulin, the efficacy of mitiglinide combined with insulin has yet to be established. We investigated the efficacy of mitiglinide combined with insulin glargine, the first soluble insulin analog that has a flat and prolonged effect. After control with the intensive regimen (daily aspart insulin and glargine), 30 inpatients with type 2 diabetes were switched to premeal mitiglinide combined with once daily insulin glargine (mitiglinide regimen), and daily profiles of blood glucose level were compared under each regimen. Fifteen patients showed similar control of hyperglycemia with mitiglinide regimen and intensive insulin regimen, assessed by M value (<32), while the remaining 15 showed worsening under the mitiglinide regimen. The patients who were well controlled with mitiglinide regimen were significantly younger (51.9 +/- 16.0 years, p<0.005) and heavier (body mass index: 25.7 +/- 3.3 kg/m(2), p<0.05) than those who were not (67.9 +/- 8.7 and 23.0 +/- 3.1, respectively). Moreover, insulin doses of aspart per body weight were significantly fewer in effective group than in ineffective group. Duration of diabetes was shorter in the effective group, albeit insignificantly. Previous treatment before starting intensive insulin regimen, such as insulin and sulfonylurea, was not different between the two groups. Our results suggest that mitiglinide plus insulin glargine combination therapy is useful for lowering both fasting and postprandial hyperglycemia in a subpopulation of type 2 diabetes. The long-term effects of such treatment need to be established in future studies.     

甘精胰岛素和格列美脲对初诊2型糖尿病疗效的比较

目的对HbA1c〉9％的新诊断的2型糖尿病（T2DM）患者进行甘精胰岛素或格列美脲联合二甲双胍的短期强化治疗,探讨两种强化方案的疗效。方法36例新诊断的T2DM患者随机分为两组,每组18例,分别使用甘精胰岛素或格列美脲联合二甲双胍治疗,疗程12周,对其在治疗前后血糖控制情况及胰岛β细胞功能进行自身及组间比较。结果治疗后两组FPG、2hPG、HbA1c均显著下降（P均〈0．01）,HOMA-IR下降（P〈0．05）,HOMA-β升高（P〈0．01）。FPG、2hPG、HbA1C治疗前后的差值及治疗12周后早餐前后血糖差值,两组间比较差异均有统计学意义（P均〈0．05）,甘精组血糖达标更迅速。结论HbA1c〉9％的新诊断的T2DM患者两种短期强化方案疗效均佳,且胰岛素组降糖更显著、迅速。     

甘精胰岛素和格列齐特缓释片对初诊2型糖尿病患者的疗效比较

目的对糖化血红蛋白（HbAlc）在8％～10％的初诊为2型糖尿病的患者,在饮食、运动治疗的基础上,采用“甘精胰岛素加阿卡波糖”或“格列齐特缓释片加阿卡波糖”进行短期强化治疗,比较两种方案的疗效。方法将60例初诊的2型糖尿病患者随机分为两组,甘精胰岛素组采用甘精胰岛素联用阿卡波糖治疗,格列齐特组采用格列齐特缓释片联用阿卡波糖治疗,共12周,观察两组患者治疗前后血糖、糖化血红蛋白（HbAlc）、空腹胰岛素（Fins）、餐后胰岛素（2hIns）、胰岛素抵抗指数（HOMA—IR）及胰岛素分泌指数（HOMA—β）的变化。结果两种治疗方案均能显著降低血糖及HbAlc（P〈0．01）,Fins升高（P〈0．05）,HOMA—IR下降（P〈0．05）,HOMA-β升高（P〈0．01）,低血糖发生率低。甘精胰岛素组降低血糖的效果优于格列齐特组（P〈0．05）。结论两种强化方案对HbAlc在8％～10％的初诊2型糖尿病患者均有较好的疗效,且甘精胰岛素组降糖效果更加显著。     

甘精胰岛素联合赖脯胰岛素强化治疗2型糖尿病临床疗效和安全性观察

目的探讨甘精胰岛素联合赖脯胰岛素强化治疗2型糖尿病的临床疗效和安全性。方法选取确诊为2型糖尿病的患者120例作为研究对象,将患者按照随机数字表法分为对照组和观察组,每组60例,对照组采用诺和灵R联合诺和灵N进行治疗,观察组采用甘精胰岛素联合赖脯胰岛素进行治疗,比较两组患者的临床疗效和安全性。结果观察组患者治疗后的总有效率(90.00%)明显高于对照组(65.00%),观察组患者治疗后低血糖发生率(13.33%)明显低于对照组(41.67%),两组比较差异具有统计学意义(P0.05)。结论对2型糖尿病患者采用甘精胰岛素联合赖脯胰岛素进行强化治疗能够取得较好的临床效果,可以降低患者治疗后低血糖的发生率,值得在临床中推广应用。     

Comparison of insulin detemir and insulin glargine in subjects with Type 1 diabetes using intensive insulin therapy.

AIMS: To compare glycaemic control and risk of hypoglycaemia of twice-daily insulin detemir with once-daily insulin glargine in subjects with Type 1 diabetes. METHODS: In this 26-week, multicentre, open-label, parallel-group trial, 320 subjects with Type 1 diabetes received either insulin detemir twice daily or insulin glargine once daily. each in combination with premeal insulin aspart. RESULTS: After 26 weeks, HbA(1c) had decreased from 8.8 to 8.2% in the insulin detemir group and from 8.7 to 8.2% in the insulin glargine group. Home-measured fasting plasma glucose (PG) was lower with insulin glargine than with insulin detemir (7.0 vs. 7.7 mmol/l, P < 0.001). The overall shape of the home-measured nine-point PG profiles was comparable between treatments (P = 0.125). Overall, there was no significant difference in within-subject variation in PG (P = 0.437). Within-subject variation in predinner PG was lower with insulin detemir than with insulin glargine (P < 0.05). The overall risk of hypoglycaemia was similar with no differences in confirmed hypoglycaemia. However, the risk of severe and nocturnal hypoglycaemia was 72% and 32%, respectively, lower with insulin detemir than with insulin glargine (P < 0.05). Body weight gain was not significantly different comparing insulin detemir and insulin glargine (0.52 kg vs. 0.96 kg, P = 0.193). CONCLUSIONS: Treatment with twice-daily insulin detemir or once-daily insulin glargine, each in combination with insulin aspart, resulted in similar glycaemic control. The overall risk of hypoglycaemia was comparable, whereas the risks of both severe and nocturnal hypoglycaemia were significantly lower with insulin detemir.     

Glycemic control and safety in Chinese patients with type 2 diabetes mellitus who switched from premixed insulin to insulin glargine plus oral antidiabetics: a large,prospective, observational study

In some circumstances, the premixed insulin should be switched to alternative therapy. The effectiveness and the safety of switching from premixed insulin to insulin glargine plus oral antidiabetic drugs (OADs) in Chinese patients with type 2 diabetes mellitus (T2DM) have not been clarified and, hence, will be assessed in this study. Chinese patients with T2DM (2013 men and women aged 18–75 years) who had received premixed insulin ± OADs for ≥3 months with glycated hemoglobin (HbA1c) ≤ 10% were enrolled in a prospective, observational study conducted at 53 hospitals across China. At baseline and at the discretion of the physician, patients switched from premixed insulin to insulin glargine plus OADs. Changes in HbA1c, fasting plasma glucose (FPG), 2‐hour postprandial glucose (PPG), treatment satisfaction, and the incidence of hypoglycemia were assessed for 16 weeks. In total, 1850 patients completed the study. Mean HbA1c level for the group decreased significantly (from 7.8% ± 1.2% at week 1 to 7.0% ± 1.0% at week 16; P  < .0001), and 55.2% of patients achieved HbA1c < 7% at week 16. Mean FPG and 2‐hour PPG decreased significantly (−1.4 ± 2.2 and −2.1 ± 3.9 mmol/L, respectively; both P  < .0001), whereas patient satisfaction improved significantly. Adverse events were reported in 18.7% of patients. Chinese patients with T2DM who switched from premixed insulin to insulin glargine plus OADs achieved significantly improved glycemic control and treatment satisfaction with a low incidence of hypoglycemia. Patients who are most likely to achieve the HbA1c target less than 7% are younger, have shorter disease duration, and have lower baseline HbA1c and FPG levels.     

Comparison of insulin lispro protamine suspension versus insulin glargine once daily in basal-bolus therapies with insulin lispro in type 2 diabetes patients: a prospective randomized open-label trial

Aims: To compare the efficacy and safety of insulin lispro protamine suspension (ILPS) versus insulin glargine once daily in a basal‐bolus regimen in type 2 diabetes mellitus (T2DM) patients. Methods: Three hundred eighty‐three insulin‐treated patients were randomized to either ILPS plus lispro or glargine plus lispro in this open‐label 24‐week European study. Insulin doses were titrated to predefined blood glucose (BG) targets. Non‐inferiority of ILPS versus glargine was assessed by comparing the upper limit of the 95% confidence interval (CI) for the change of HbA1c from baseline to week 24 (adjusted for country and baseline HbA1c) with the non‐inferiority margin of 0.4%. Secondary endpoints included HbA1c categories, BG profiles, insulin doses, hypoglycaemic episodes, adverse events and vital signs. Results: Non‐inferiority of ILPS versus glargine in the change of HbA1c from baseline was shown: least‐square mean between‐treatment difference (95% CI) was 0.1% (?0.11; 0.31). Mean changes at week 24 were ?1.05% (ILPS) and ?1.20% (glargine). HbA1c <7.0% was achieved by 21.7 versus 29.4% of patients. Mean basal/mealtime insulin doses at week 24 were 29.6/36.2 IU/day (ILPS) versus 32.8/42.2 IU/day (glargine); the difference was not statistically significant for total dose (p = 0.7). In both groups, 56.1/25.7% versus 63.6/19.3% of patients experienced any/nocturnal hypoglycaemia (p = 0.2 for both). No relevant differences were noted in any other variables. Conclusions: A basal‐bolus regimen with ILPS once daily resulted in non‐inferior glycaemic control compared to a similar regimen with glargine, without statistically significant or clinically relevant differences in hypoglycaemia. ILPS‐based regimens can be considered an alternative to basal‐bolus regimens with glargine for T2DM patients.     

甘精胰岛素联合格列美脲对比联合吡格列酮治疗新诊断2型糖尿病的疗效观察

目的 比较甘精胰岛素联合格列美脲对比联合吡格列酮治疗新诊断HbA1 c＞9.0％的T2DM患者的疗效与安全性. 方法 新诊断的T2DM患者92例随机分为甘精胰岛素联合格列美脲（A）组和联合吡格列酮（B）组,观察治疗前后,两组BMI、FPG、2 hPG、HbA1 c、胰岛β细胞功能、血糖达标时间、胰岛素单日用量及低血糖发生率. 结果 12周后,两组FPG、2hPG、HbA1c、HOMA-IR均比治疗前下降（P＜0.01）;FC-P、2 hC-P、胰岛素功能指数（HOMA-islet）均升高（P＜0.01）;B组治疗后较治疗前体重增加（P＜0.05）,而A组无明显变化（P＞0.05）;与B组比较,A组达标时间短,单日胰岛素用量少、体重增加少,且低血糖发生率低（P＜0.05）. 结论 甘精胰岛素联合格列美脲与联合吡格列酮治疗新诊断T2DM均能较好地控制血糖,但甘精胰岛素联合格列美脲低血糖发生率更低,体重增加更少.     

预混胰岛素转换为甘精胰岛素联合口服降糖药有效性与安全性的观察

目的 评价应用预混胰岛素治疗血糖控制不佳的T2DM患者转换为甘精胰岛素联合口服药物治疗的有效性及安全性. 方法 选择62例应用预混胰岛素治疗但血糖控制不佳的T2DM患者,将其治疗方案转换为甘精胰岛素联合口服药治疗16周.以治疗前后FPG、2hPG及HbA1c的变化评价方案的有效性和低血糖发生率及BMI的变化评价治疗的安全性,采用调查问卷评分比较治疗前后满意度. 结果 治疗16周后,FPG、2hPG及HbA1c较治疗前下降(P＜0.01),HbA1c下降幅度大于1％者占63.79％;治疗期间共有16例发生非重度日间低血糖27次;患者对治疗的满意度较治疗前增加(P＜0.01). 结论 应用预混胰岛素治疗但血糖控制不佳的T2DM患者转换为甘精胰岛素联合口服药物治疗具有安全性、有效性.     

每日1次地特胰岛素在2型糖尿病胰岛素起始治疗及强化治疗中的应用

随着疾病的进展。多数T2DM患者最终需要接受胰岛素治疗。目前,得到广泛公认的药物治疗途径是由口服降糖药经过单一胰岛素逐渐过渡至多次、多种胰岛素注射治疗。无论是在胰岛素起始治疗中,还是在强化胰岛素治疗（基础胰岛素＋餐时胰岛素方案）中,地特胰岛素的疗效都得到了证实,且相对于其他基础胰岛素而言,具有低血糖风险小、增重少、个体血糖更加稳定的优势。     

Comparison of tiotropium once daily, formoterol twice daily and both combined once daily in patients with COPD.

This study compared the bronchodilator effects of tiotropium, formoterol and both combined in chronic obstructive pulmonary disease (COPD). A total of 71 COPD patients (mean forced expiratory volume in one second (FEV1) 37% predicted) participated in a randomised, double-blind, three-way, crossover study and received tiotropium 18 microg q.d., formoterol 12 microg b.i.d. or both combined q.d. for three 6-week periods. The end-points were 24-h spirometry (FEV1, forced vital capacity (FVC)) at the end of each treatment, rescue salbutamol and safety. Compared with baseline (FEV1 prior to the first dose in the first period), tiotropium produced a significantly greater improvement in average daytime FEV1 (0-12 h) than formoterol (127 versus 86 mL), while average night-time FEV1 (12-24 h) was not different (tiotropium 43 mL, formoterol 38 mL). The most pronounced effects were provided by combination therapy (daytime 234 mL, night-time 86 mL); both differed significantly from single-agent therapies. Changes in FVC mirrored the FEV1 results. Compared with both single agents, daytime salbutamol use was significantly lower during combination therapy (tiotropium plus formoterol 1.81 puffs.day(-1), tiotropium 2.41 puffs x day(-1), formoterol 2.37 puffs x day(-1)). All treatments were well tolerated. In conclusion, in chronic obstructive pulmonary disease patients, tiotropium q.d. achieved a greater improvement in daytime and comparable improvement in night-time lung function compared with formoterol b.i.d. A combination of both drugs q.d. was most effective and provided an additive effect throughout the 24-h dosing interval.     

达格列净联合短期胰岛素强化治疗对初治2型糖尿病患者代谢指标的影响

目的探讨新诊断2型糖尿病（T2DM）患者在短期胰岛素强化治疗的基础上联用达格列净对代谢指标的影响。 方法入选2018年5月至2020年8月于东莞东华医院内分泌科住院的新诊断T2DM患者60例,随机分为试验组（短期胰岛素强化+达格列净）和对照组（短期胰岛素强化）,收集治疗前（d0）、血糖达标后14天（D14）及停药后随访第12周（W12）的资料,分析两组患者的代谢指标的变化。 结果两组患者的体重、体质量指数（BMI）及腰围在W12时仍出现明显下降,且试验组下降更显著;试验组的血尿酸（UA）在D14出现明显下降,但停药后明显回升,而对照组的UA治疗前后无明显变化;两组患者的甘油三酯（TG）、总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）在治疗后均出现明显下降,试验组高密度脂蛋白胆固醇（HDL-C）在停药后明显升高,而对照组治疗前后无明显变化。 结论对于新诊断的T2DM患者,在早期胰岛素强化降糖的同时加用达格列净治疗,可更显著减少体重、BMI、腰围,改善患者HDL-C等代谢指标。     

A quality-of-life assessment of intensive insulin therapy using insulin lispro switched from short-acting insulin and measured by an ITR-QOL questionnaire: a prospective comparison of multiple daily insulin injections and continuous subcutaneous insulin infusion

We examined quality-of-life (QOL) of patients with a prospective comparison of multiple daily insulin injections therapy (16 patients in MDI group) and continuous subcutaneous insulin infusion therapy (12 patients in CSII group) using insulin lispro (LP), which was switched from short-acting insulin on the basis of a questionnaire about insulin-therapy-related QOL measure (ITR-QOL). The overall score of ITR-QOL before using LP in the CSII group was significantly higher (P<0.02) than the MDI group. In four subscales of ITR-QOL, the scores of social and daily activities and of therapy-related feelings in the CSII group were significantly higher (P<0.02) than those in the MDI group, respectively, while there was no significant difference in the score of physical function between the two groups. Three months after using LP, the score of daily activities in the MDI group was significantly higher (P<0.02) than that before using LP, while there were no significant differences in other scores of the two groups. There were no significant differences in HbA1c between two groups before and after using LP. The frequency of hypoglycemic events in the MDI group before using LP was higher than that in the CSII group and decreased after using LP. These results show that QOL of patients treated by CSII is superior to that treated by MDI and demonstrate that insulin lispro has a more beneficial effect on daily activities in patients treated by MDI than short-acting insulin.     

The effect duration of candesartan cilexetil once daily, in comparison with enalapril once daily, in patients with mild to moderate hypertension

OBJECTIVE: To determine the antihypertensive efficacy, effect duration and safety of the angiotensin II type 1 receptor blocker candesartan cilexetil and the angiotensin converting enzyme inhibitor enalapril once daily in patients with mild to moderate hypertension. METHODS: A multicenter, randomised, double-blind parallel group study was performed in Finland, France, the Netherlands, Spain and Sweden. Three-hundred-and-ninety-five men and women in the age range 20-80 years with primary hypertension were randomised to an 8-week double-blind treatment period with either candesartan cilexetil 8-16 mg or enalapril 10-20 mg once daily, with forced dose titration after 4 weeks. Non-invasive ambulatory blood pressure was measured for 36 h at baseline and after 8 weeks. The primary efficacy variable was the change in mean diastolic and systolic ambulatory blood pressure 22-24 h post-dose. RESULTS: There was a significant difference in the adjusted mean difference for the change from baseline to week 8 between candesartan cilexetil and enalapril 22-24 h post-dose by -3.5 mmHg (95% confidence interval, CI: -6.8 to -0.3 mmHg; p < 0.032) in ambulatory systolic blood pressure and -3.0 mmHg (95% CI: -5.1 to -0.8 mmHg; p < 0.008) in ambulatory diastolic blood pressure. There was a significant difference in adjusted mean daytime ambulatory blood pressure 24-36 h post-dose by -4.2 mmHg (95% CI: -6.8 to -1.6 mmHg; p < 0.002)/-3.5 mmHg (95% CI: -5.1 to -1.8 mmHg; p < 0.001). Both drugs were generally well tolerated. CONCLUSION: The results of the present study suggest that advantages may be attributed to the use of candesartan cilexetil, as compared to enalapril in the treatment of patients with essential hypertension. In comparison with enalapril 20 mg, candesartan cilexetil 16 mg more effectively lowered blood pressure at trough and in particular on the day following the day after the last dose.     

A randomised,multinational study with sequential therapy comparing ciprofloxacin twice daily and ofloxacin once daily

Summary In a multinational, open, randomised, controlled clinical study, 474 hospitalised patients with moderate or severe infections were treated with sequential regimens of ofloxacin or ciprofloxacin. Ofloxacin 400 mg once daily or ciprofloxacin 200 mg twice daily were given intravenously for at least 3 days followed by oral treatment with ofloxacin 400 mg once daily or ciprofloxacin 500 mg twice daily. Overall cure rates of 86.8% (85.7%) in the ofloxacin group and 89.6% (89.5%) in the ciprofloxacin group were achieved in the intention-to-treat analysis (per protocol analysis). The overall bacteriological response rate (ofloxacin 89.5%, ciprofloxacin 89.0%) was comparable to the clinical cure rate. Both drugs were well tolerated and adverse events were rarely observed. It is concluded that ofloxacin and ciprofloxacin can be used successfully in the treatment of hospitalised patients with aerobic gram-positive and gram-negative infections. Ofloxacin has the advantage of a oncedaily regimen, compared to the twice-daily regimen with ciprofloxacin.

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Randomisierte, multinationale Studie mit einer sequentiellen Therapie, die Ciprofloxacin zweimal täglich mit Ofloxacin einmal täglich vergleicht

Zusammenfassung In einer multinationalen, offenen, randomisierten, kontrollierten klinischen Studie wurden 474 hospitalisierte Patienten mit mittelschweren oder schweren Infektionen mit einer sequentiellen Therapie behandelt. Für mindestens 3 Tage wurde Ofloxacin 400 mg 1× täglich oder Ciprofloxacin 200 mg 2× täglich intravenös verabreicht. Anschließend wurde die Therapie oral fortgesetzt mit 400 mg Ofloxacin 1× täglich oder 500 mg Ciprofloxacin 2× täglich. Die Heilungsrate betrug 86,8% (85,7%) in der Ofloxacin- und 89,6% (89,5%) in der Ciprofloxacin-Gruppe in der intention-to-treat-Analyse (per-protocol-Analyse). Die bakteriologische Wirksamkeit (Ofloxacin 89,5%, Ciprofloxacin 89,0%) war der klinischen Heilungsrate vergleichbar. Nebenwirkungen wurden selten beobachtet, die Verträglichkeit der beiden Therapien war gut. Die Ergebnisse haben gezeigt, daß Ofloxacin und Ciprofloxacin erfolgreich in der Behandlung hospitalisierter Patienten mit grampositiven (Aerobier) und gramnegativen Infektionen eingesetzt werden kann. Ofloxacin hat den Vorteil der Einmalgabe, Ciprofloxacin muß 2× am Tag verabreicht werden.