Combination of oral antidiabetic agents with basal insulin versus premixed insulin alone in randomized elderly patients with type 2 diabetes mellitus

OBJECTIVES: To compare initiation of insulin therapy by adding once-daily insulin glargine to oral antidiabetic agents (OADs) with switching patients to premixed 30% regular, 70% human neutral protamine hagedorn insulin (70/30) without OADs. DESIGN: A 24-week, multicenter, open, randomized (1:1), parallel study. SETTING: Three hundred sixty-four poorly controlled patients with type 2 diabetes mellitus were treated with once-daily morning insulin glargine with continued OADs (glimepiride+metformin) (glargine+OAD) or twice-daily 70/30 alone. Insulin dosage in each group was titrated to target fasting blood glucose (FBG) of 100 mg/dL or less (or=6.7 mmol/L) and hemoglobin (Hb)A(1c) levels between 7.5% and 10.5% on OADs (glargine+OAD, n=67; 70/30, n=63). MEASUREMENTS: HbA(1c), FBG, hypoglycemia, insulin dose, and adverse events were recorded. RESULTS: HbA(1c) decreased from baseline to endpoint for both glargine+OAD (from 8.8% to 7.0%) and 70/30 (from 8.9% to 7.4%); adjusted mean HbA(1c) decrease for glargine+OAD and 70/30 was -1.9% and -1.4%, respectively (P=.003). More patients reached HbA(1c) of 7.0% or less without confirmed nocturnal hypoglycemia with glargine+OAD (n=37, 55.2%) than with 70/30 (n=19, 30.2%) (P=.006). FBG decreased significantly more with glargine+OAD (-57 mg/dL (-3.2 mmol/L)) than with 70/30 (-40 mg/dL (-2.2 mmol/L)) (P=.002). Patients treated with glargine+OAD experienced fewer episodes of any hypoglycemia (3.68/patient-year) than did those treated with 70/30 (9.09/patient-year) (P=.008). CONCLUSION: In elderly patients, addition of once-daily morning glargine+OAD is a simple regimen to initiate insulin therapy, restoring glycemic control more effectively and with less hypoglycemia than twice-daily 70/30 alone.     

Comparison of insulin detemir and insulin glargine using a basal‐bolus regimen in a randomized,controlled clinical study in patients with type 2 diabetes

Background

This treat‐to‐target study compared the efficacy and safety of insulin detemir (IDet) and insulin glargine (IGla) in a basal‐bolus (insulin aspart) regimen in type 2 diabetes.

Methods

385 patients were randomized 2 : 1 (IDet : IGla). Non‐inferiority of IDet to IGla was determined by HbA_1c 95% CI upper limit <0.4.

Results

IDet and IGla showed similar efficacy in HbA_1c reduction at 26 weeks, as the non‐inferiority criterion was met at 26 weeks (LS mean [Det–Gla]: 0.207; 95% CI: 0.0149,0.3995). It appeared that IGla in some cases did better than IDet in terms of HbA_1c, but the difference (0.207%) was not clinically meaningful. Based on the CONSORT guideline, non‐inferiority analysis using the LOCF approach was inconclusive regarding possible inferiority of delta 0.4 (LS mean of [Det–Gla]: 0.307; 95% CI: 0.1023, 0.5109). HbA_1c decreased significantly from baseline in IDet (?1.1% [26 weeks], ?0.9% [LOCF], p < 0.001) and in IGla (?1.3% [26 weeks, LOCF], p < 0.001). Final HbA_1c were 7.1% (26 weeks) and 7.3% (LOCF) in IDet, and 6.9% (26 weeks) and 7.0% (LOCF) in IGla. Final FPG were 130 mg/dL (26 weeks) and 135 mg/dL (LOCF) in IDet, and 134 mg/dL (26 weeks) and 137 mg/dL (LOCF) in IGla. There was significantly less weight gain in IDet‐treated patients (1.2 ± 3.96 kg versus 2.7 ± 3.94 kg, p = 0.001). Hypoglycemia risk was comparable between groups. The majority of IDet‐treated patients (87.4%) remained on a once‐daily basal insulin regimen throughout the study.

Conclusions

IDet and IGla were both effective and safe treatments for glycemic control in a basal‐bolus regimen for type 2 diabetes. Clinically significant reductions in HbA_1c were achieved in both groups, but with significantly less weight gain in the IDet group at comparable basal insulin dosage. Copyright © 2009 John Wiley & Sons, Ltd.

     

Effects of basal and premixed insulin on glycemic control in type 2 diabetes patients based on multicenter prospective real‐world data

BackgroundTo investigate the different efficacies of glycemic control between basal and premixed insulin in participants with type 2 diabetes (T2DM) when non‐insulin medications fail to reach treatment targets.MethodsThis was a prospective, large‐scale, real‐world study at 10 diabetes centers in China. Between June 2017 and June 2021, we enrolled 1104 T2DM participants initiated with either once‐daily basal insulin or twice‐daily premixed insulin when the glycosylated hemoglobin (HbA1c) control target was not met after at least two non‐insulin agents were administered. A Cox proportional hazards regression model adjusting for multiple influencing factors was performed to compare the different effects of basal and premixed insulin on reaching the HbA1c control target.ResultsAt baseline, basal insulin (57.3%) was prescribed more frequently than premixed insulin (42.7%). Patients with a higher body mass index (BMI) or higher HbA1c levels were more likely to receive premixed insulin than basal insulin (both p < 0.001). After a median follow‐up of 12.0 months, compared to those with premixed insulin, the hazard ratio for reaching the HbA1c target to those with basal insulin was 1.10 (95% CI, 0.92‐1.31; p = 0.29) after adjustment, and less weight gain was observed in those with basal insulin than with premixed insulin (percentage change of BMI from baseline −0.37[5.50]% vs 3.40[6.73]%, p < 0.0001).ConclusionsIn this real‐world study, once‐daily basal insulin was more frequently prescribed and had similar glycemic control effects but less weight gain compared with twice‐daily premixed insulin when used as initiation therapy for those in whom glycemic control with non‐insulin medications failed.     

Prandial-basal insulin regimens plus oral antihyperglycaemic agents to improve mealtime glycaemia: initiate and progressively advance insulin therapy in type 2 diabetes

Aims: To compare two progressive approaches [once‐daily insulin glargine plus ≤3 mealtime lispro (G+L) vs. insulin lispro mix 50/50 (LM50/50) progression once up to thrice daily (premix progression, PP)] of beginning and advancing insulin in patients with type 2 diabetes (T2D) and inadequate glycaemic control on oral therapy, with the aim of showing non‐inferiority of PP to G+L. Methods: Patients were randomized to PP (n = 242) or G+L (n = 242) in a 36‐week, multinational, open‐label trial. Dinnertime insulin LM 50/50 could be replaced with insulin lispro mix 75/25 if needed for fasting glycaemic control. Results: Baseline haemoglobin A1c (HbA1c) were 9.5% (PP) and 9.3% (G+L); p = 0.095. Change in A1C (baseline to endpoint) was ?1.76% (PP) and ?1.93% (G+L) (p = 0.097) [between‐group difference of 0.17 (95% confidence interval: ?0.03, 0.37)]. Non‐inferiority of PP to G+L was not shown based on the prespecified non‐inferiority margin of 0.3%. A1C was lower with G+L at weeks 12 (7.8 vs. 7.9%; p = 0.042), 24 (7.4 vs. 7.6%; p = 0.046), but not at week 36 (7.5 vs. 7.6%; p = 0.405). There were no significant differences in percentages of patients achieving A1C ≤7%, overall hypoglycaemia incidence and rate or weight change. Total daily insulin dosages at endpoint were higher with PP vs. G+L (0.57 vs. 0.51 U/kg; p = 0.017), likely due to more injections (1.98 vs. 1.79; p = 0.011). Conclusions: Both treatments progressively improved glycaemic control in patients with T2D on oral therapy, although non‐inferiority of PP to G+L was not shown. Higher insulin doses were observed with PP with no between‐treatment differences in overall hypoglycaemia or weight gain.     

预混胰岛素治疗的2型糖尿病患者转为甘精胰岛素联合口服药治疗的疗效分析

目评价甘精胰岛素联合口服降糖药物(OADs)治疗方案对使用预混胰岛素血糖控制欠佳的2型糖尿病患者的疗效及安全性.方法 预混胰岛素30/70单独或联合使用OADs血糖控制不良的2型糖尿病患者50例,随机分为治疗组(停用预混胰岛素,改为皮下注射甘精胰岛素联合OADs,n=30)和对照组(继续使用预混胰岛素早、晚餐前皮下注射...     

Insulin glargine benefits patients with type 2 diabetes inadequately controlled on oral antidiabetic treatment: an observational study of everyday practice in 12,216 patients

AIMS: This observational study aimed to investigate the long-term efficacy and safety of adding insulin glargine (LANTUS((R))) to support oral antidiabetic (OAD) treatment in patients with type 2 diabetes in everyday practice. METHODS: A 9-month, open-label, multicentre, observational study, with an optional 20-month extension phase, in which add-on insulin glargine therapy was initiated in 12,216 patients with type 2 diabetes inadequately controlled on OADs. The insulin glargine dose was adjusted at the physician's discretion, reflecting everyday practice. The main outcome measures were changes in HbA(1c), fasting blood glucose (FBG), insulin dose and body mass index (BMI). RESULTS: At baseline, mean (+/- s.d.) age was 63.9 +/- 11.3 years; disease duration was >5 years in 47% of patients, 1-5 years in 39% of patients and <1 year in 10% of patients, while 4% of patients were newly diagnosed. Addition of insulin glargine to OAD therapy led to reductions in mean HbA(1c) (-1.5% from 8.7%) and FBG (-69 mg/dl from 202 mg/dl) levels after 3 months, which were maintained after 9 months [HbA(1c): -1.7%; FBG: -71 mg/dl (-3.9 mmol/l)] without an increase in BMI. Similar glycaemic control was observed after 20 months in the 2721 patients in the extension study. Adverse drug reactions were documented in 26 patients (0.2%). Of 47 adverse events documented, 19 were due to hypoglycaemia. CONCLUSIONS: In everyday practice, patients with type 2 diabetes who are inadequately controlled on OADs benefit from add-on basal insulin treatment with insulin glargine as they demonstrate improved glycaemic control without weight gain.     

2型糖尿病胰岛素治疗中诺和锐30和诺和灵30R的对比研究

目的比较诺和锐30和诺和灵30R每日2次皮下注射治疗在开始胰岛素治疗的2型糖尿病（T2DM）患者的疗效和安全性。方法为期12周的随机、开放性比较研究。72例T2DM患者被随机分为诺和锐30治疗组和诺和灵30R治疗组，采用每日早、晚餐前两次皮下注射方案，观察两组患者7个时点血糖、糖化血红蛋白（HbA1c）、低血糖事件及其他不良事件的差异。结果诺和锐30治疗组三餐后血糖水平明显低于诺和灵30R治疗组（P〈0．05）；诺和锐30组低血糖发生次数低于诺和灵30R组，严重低血糖发生次数约为诺和灵30R组的50％；两组HbA1c、胰岛素用量及其他不良事件差异无统计学意义。结论T2DM患者采用早、晚餐前预混胰岛素皮下注射方案治疗时，诺和锐30对餐后血糖控制更为满意，且低血糖事件发生率少；两种治疗之间的总体血糖控制水平相似。     

Efficacy and safety of LY2963016 insulin glargine in patients with type 1 and type 2 diabetes previously treated with insulin glargine

The safety and efficacy of LY2963016 insulin glargine (LY IGlar) and Lantus^® insulin glargine (IGlar), products with identical primary amino acid sequences, were assessed in subgroups of patients with type 1 (T1D, n = 452) or type 2 diabetes (T2D, n = 299) reporting prestudy IGlar treatment in 52‐week open‐label (ELEMENT‐1) and 24‐week double‐blind (ELEMENT‐2) studies. At randomization, patients transitioned from their prestudy IGlar to equivalent doses of LY IGlar or IGlar. Primary efficacy (change in glycated haemoglobin from baseline to 24 weeks), other efficacy and select safety outcomes of LY IGlar were compared with those of IGlar. Continuous data were analysed using analysis of covariance, categorical data by Fisher's exact test, and treatment comparisons for hypoglycaemia by Wilcoxon test. No statistically significant treatment differences were identified for efficacy and safety outcomes except for weight change (T1D), overall incidence of detectable insulin antibodies (T2D), and serious adverse events (T2D). These differences were neither consistently observed across both studies nor observed in the total study populations, and their magnitude suggests they were not clinically meaningful. LY IGlar and IGlar show similar efficacy and safety profiles in patients reporting prestudy IGlar treatment.     

An observational study comparing continuous subcutaneous insulin infusion (CSII) and insulin glargine in children with type 1 diabetes

OBJECTIVE: The advantages of continuous subcutaneous insulin infusion (CSII) or insulin glargine have been demonstrated both in adult and paediatric diabetic patients; however, as no data comparing these two approaches during childhood are available, we have examined the efficacy of these two intensive approaches. RESEARCH DESIGN AND METHODS: We retrospectively evaluated data from 36 diabetic children, who had changed their previous insulin regimen [with isophane insulin (NPH) at bedtime] because of HbA1c levels >8.0%. Twenty patients underwent CSII, while the other 16 (significantly younger for age) started insulin glargine at bedtime. RESULTS: At 6 and 12 months, CSII-treated patients showed a significant reduction in HbA1c values from 8.5 +/- 1.8 to 7.4 +/- 1.1% and to 7.6 +/- 1.2%, respectively. The insulin requirement significantly decreased from 0.93 +/- 0.2 IU/kg to 0.73 +/- 0.2 IU/kg of body weight and to 0.74 +/- 0.15 IU/kg of body weight, respectively, while no significant differences were observed for BMI SDS, fructosamine and severe hypoglycaemic events. The patients treated with glargine showed a small decline in HbA1c values from 8.9 +/- 1.7 to 8.3 +/- 0.9% (not significant) in the first 6 months of treatment and to 8.2 +/- 0.9% after 12 months. CONCLUSION: The basal insulin supplementation can be supplied effectively in children with type 1 diabetes by either CSII or insulin glargine. As previously reported for adults, it is confirmed that CSII is the best current intensive approach aimed to the improvement of glycaemic control.     

Options for the intensification of insulin therapy when basal insulin is not enough in type 2 diabetes mellitus

In the early treatment of type 2 diabetes mellitus (T2DM), the addition of a basal insulin, such as insulin glargine, to existing oral therapy can help patients attain recommended glycaemic control targets, including haemoglobin A_1c (HbA_1c) <7% and fasting blood glucose <5.5 mmol/l (<100 mg/dl). For patients close to but not at target, the management of postprandial glucose excursions with a rapid-acting insulin, such as insulin glulisine, can provide further improvements in glycaemic control. In this review, the options for intensifying insulin therapy with the addition of one or more daily doses of prandial insulin are discussed. In addition, the advantages/disadvantages of choosing a basal–bolus vs. a premixed insulin strategy are discussed. A conceptually simple approach for the treatment of T2DM is for optimization of the basal insulin dose (added to oral antidiabetic drugs) to target fasting glycaemia followed by the addition of a single prandial dose of rapid-acting insulin to target the largest glucose excursion. A second and third dose of prandial insulin can then be added if HbA_1c remains above target and to manage postprandial glucose excursions at other meals. Prospective studies are underway to further examine this concept and determine the benefit of this approach not only on overall glycaemic control but also on cardiovascular risk.     

Insulin management in overweight or obese type 2 diabetes patients: the role of insulin glargine

Type 2 diabetes mellitus (T2DM) and obesity commonly co-exist. Improved clinical management of T2DM and improved glycaemic control with traditional therapies including insulin usually result in some weight gain – a frequently perceived barrier to the introduction of insulin by both patient and healthcare professionals. Weight gain of 2.5 kg per 1% change in haemoglobin A_1c (HbA_1c) is common in many studies. Strategies to minimize weight gain, particularly in obese patients, are essential to help patients better manage their diabetes and improve quality of life. Insulin analogues with lower risk of hypoglycaemia and better within-patient variability compared with human insulin may help facilitate reaching treatment goals. Moreover, weight gain can be minimized by earlier insulinization and the use of basal insulin, such as insulin glargine, instead of premixed insulin. Data specific to the obese patient with T2DM are presented; they are currently limited but do indicate that insulin glargine therapy is associated with improved glycaemic control as well as less weight gain than other insulins, such as premixed insulin and prandial insulin regimens. Retrospective subanalyses of earlier trials and ongoing studies would shed further light on the impact of insulin therapy in obese people with T2DM in addition to determination of optimal therapeutic strategies.     

甘精胰岛素300 U/ml与100 U/ml治疗中国2型糖尿病患者疗效和安全性的比较

目的比较甘精胰岛素300 U/ml(Gla-300)与100 U/ml(Gla-100)治疗非胰岛素类降糖药血糖控制不佳中国T2DM患者的疗效和安全性。方法本研究为EDITION AP(NCT02855684)中国亚组分析,在这项开放标签、随机对照的临床试验中,非Ins类降糖药物血糖控制不佳的474例中国T2DM患者按2:1比例随机予Gla-300(n=315)或Gla-100(n=159)治疗,观察两组26周时的疗效和安全性指标。结果两组自基线至治疗26周时HbA1c降幅的最小二乘均值差为0.05%,达到非劣效性评估终点。26周治疗期间,Gla-300组发生至少1次重度和/或证实夜间低血糖患者比例低于Gla-100组(31.5%vs 42.0%,P=0.03)。两组其余疗效和安全性指标差异无统计学意义。结论Gla-300治疗26周降低HbA1c效果与Gla-100相似,发生夜间低血糖风险更低。