Juurinen L, Tiikkainen M, Saltevo J, Nikkilä K, Lanki H, Leppävuori E, Kock T, Teikari-Myyrä T, Kauppinen-Mäkelin R, Kotronen A, Yki-Järvinen H
Helsinki University Central Hospital, Helsinki, Finland.
Diabet Med. 2009 Apr;26(4):409-15. doi: 10.1111/j.1464-5491.2009.02691.x.
To compare the effect of adding nateglinide or placebo on postprandial glucose excursions (PPGEs), glycated haemoglobin (HbA(1c)), diurnal glucose profiles and hypoglycaemia in patients with Type 2 diabetes treated with the combination of basal insulin and metformin.
This was an investigator-initiated, double-blind, randomized, parallel-group, study in five centres. Patients with Type 2 diabetes (n = 88, age 56.0 +/- 0.9 years, duration of diabetes 9.4 +/- 0.5 years, HbA(1c) 7.8 +/- 0.1%, body mass index 32.4 +/- 0.5 kg/m(2)) treated with basal insulin and metformin entered a 24-week period, during which basal insulin was titrated to optimize glucose control. Thereafter, the patients were randomized to receive either nateglinide (120 mg three times daily) or placebo before their main meals for 24 weeks.
During the optimization period, HbA(1c) decreased by -0.3 +/- 0.1 and -0.4 +/- 0.2% (NS) and insulin doses increased by 10.0 IU (2.0-32.0) [0.09 IU/kg (0.02-0.34)] and 10.0 IU (0.0-19.0) [0.11 IU/kg (0.0-0.25)] (NS) in the nateglinide and placebo groups. Mean postprandial glucose during weeks 20-24 averaged 9.0 +/- 0.3 and 10.0 +/- 0.3 mmol/l in the nateglinide and placebo groups (P = 0.025) and mean PPGE averaged 2.4 +/- 0.2 and 3.1 +/- 0.2 mmol/l, respectively (P = 0.019). At 24 weeks as compared with 0 weeks, mean HbA(1c) had decreased by 0.41 +/- 0.12% in the nateglinide group and by 0.04 +/- 0.12% in the placebo group (P = 0.023). The frequency of confirmed, symptomatic hypoglycaemia was 7.7 episodes/patient-year vs. 4.7 episodes/patient-year in the nateglinide and placebo groups (P = 0.031).
Addition of a short-acting insulin secretagogue at main meals improves postprandial hyperglycaemia during combination therapy with basal insulin and metformin, but increases the frequency of hypolycaemia.
比较在接受基础胰岛素与二甲双胍联合治疗的2型糖尿病患者中，加用那格列奈或安慰剂对餐后血糖波动（PPGEs）、糖化血红蛋白（HbA1c）、日间血糖谱及低血糖的影响。
这是一项由研究者发起的、双盲、随机、平行组研究，在五个中心进行。接受基础胰岛素和二甲双胍治疗的2型糖尿病患者（n = 88，年龄56.0±0.9岁，糖尿病病程9.4±0.5年，HbA1c 7.8±0.1%，体重指数32.4±0.5 kg/m²）进入为期24周的阶段，在此期间调整基础胰岛素剂量以优化血糖控制。此后，患者被随机分为两组，分别在主餐前服用那格列奈（120 mg，每日三次）或安慰剂，为期24周。
在优化期，那格列奈组和安慰剂组的HbA1c分别下降了-0.3±0.1%和-0.4±0.2%（无显著差异），胰岛素剂量分别增加了10.0 IU（2.0 - 32.0）[0.09 IU/kg（0.02 - 0.34）]和10.0 IU（0.0 - 19.0）[0.11 IU/kg（0.0 - 0.25）]（无显著差异）。在第20 - 24周期间，那格列奈组和安慰剂组的平均餐后血糖分别为9.0±0.3和10.0±0.3 mmol/L（P = 0.025），平均PPGE分别为2.4±0.2和3.1±0.2 mmol/L（P = 0.019）。与第0周相比，在24周时，那格列奈组的平均HbA1c下降了0.41±0.12%，安慰剂组下降了0.04±0.12%（P = 0.023）。经确认的有症状低血糖发生频率在那格列奈组和安慰剂组分别为7.7次/患者年和4.7次/患者年（P = 0.031）。
在基础胰岛素与二甲双胍联合治疗期间，主餐时加用短效胰岛素促泌剂可改善餐后高血糖，但会增加低血糖发生频率。
