N Engl J Med. 2012 Jul 26;367(4):319-28. doi: 10.1056/NEJMoa1203858. Epub 2012 Jun 11.
The provision of sufficient basal insulin to normalize fasting plasma glucose levels may reduce cardiovascular events, but such a possibility has not been formally tested.
We randomly assigned 12,537 people (mean age, 63.5 years) with cardiovascular risk factors plus impaired fasting glucose, impaired glucose tolerance, or type 2 diabetes to receive insulin glargine (with a target fasting blood glucose level of ≤95 mg per deciliter [5.3 mmol per liter]) or standard care and to receive n-3 fatty acids or placebo with the use of a 2-by-2 factorial design. The results of the comparison between insulin glargine and standard care are reported here. The coprimary outcomes were nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes and these events plus revascularization or hospitalization for heart failure. Microvascular outcomes, incident diabetes, hypoglycemia, weight, and cancers were also compared between groups.
The median follow-up was 6.2 years (interquartile range, 5.8 to 6.7). Rates of incident cardiovascular outcomes were similar in the insulin-glargine and standard-care groups: 2.94 and 2.85 per 100 person-years, respectively, for the first coprimary outcome (hazard ratio, 1.02; 95% confidence interval [CI], 0.94 to 1.11; P=0.63) and 5.52 and 5.28 per 100 person-years, respectively, for the second coprimary outcome (hazard ratio, 1.04; 95% CI, 0.97 to 1.11; P=0.27). New diabetes was diagnosed approximately 3 months after therapy was stopped among 30% versus 35% of 1456 participants without baseline diabetes (odds ratio, 0.80; 95% CI, 0.64 to 1.00; P=0.05). Rates of severe hypoglycemia were 1.00 versus 0.31 per 100 person-years. Median weight increased by 1.6 kg in the insulin-glargine group and fell by 0.5 kg in the standard-care group. There was no significant difference in cancers (hazard ratio, 1.00; 95% CI, 0.88 to 1.13; P=0.97).
When used to target normal fasting plasma glucose levels for more than 6 years, insulin glargine had a neutral effect on cardiovascular outcomes and cancers. Although it reduced new-onset diabetes, insulin glargine also increased hypoglycemia and modestly increased weight. (Funded by Sanofi; ORIGIN ClinicalTrials.gov number, NCT00069784.).
提供足够的基础胰岛素使空腹血糖水平正常化可能会降低心血管事件的风险，但这种可能性尚未经过正式检验。
我们随机分配了 12537 名（平均年龄 63.5 岁）有心血管风险因素、空腹血糖受损、葡萄糖耐量受损或 2 型糖尿病的患者，接受甘精胰岛素（目标空腹血糖水平≤95mg/dL[5.3mmol/L]）或标准治疗，并使用 2×2 析因设计接受 n-3 脂肪酸或安慰剂。这里报告的是甘精胰岛素与标准治疗比较的结果。主要复合结局是非致死性心肌梗死、非致死性卒中和心血管原因导致的死亡，以及这些事件加上血运重建或心力衰竭住院。还比较了各组之间微血管结局、新发糖尿病、低血糖、体重和癌症的发生率。
中位随访时间为 6.2 年（四分位间距，5.8 至 6.7）。胰岛素-甘精组和标准治疗组的心血管事件发生率相似：首次主要复合结局分别为每 100 人年 2.94 例和 2.85 例（危险比，1.02；95%置信区间[CI]，0.94 至 1.11；P=0.63），第二次主要复合结局分别为每 100 人年 5.52 例和 5.28 例（危险比，1.04；95%CI，0.97 至 1.11；P=0.27）。在 1456 名无基线糖尿病的参与者中，约有 30%的参与者在停止治疗后约 3 个月被诊断为新发糖尿病，而 35%的参与者被诊断为新发糖尿病（比值比，0.80；95%CI，0.64 至 1.00；P=0.05）。严重低血糖的发生率分别为每 100 人年 1.00 例和 0.31 例。甘精胰岛素组体重平均增加 1.6kg，标准治疗组体重平均下降 0.5kg。癌症无显著差异（危险比，1.00；95%CI，0.88 至 1.13；P=0.97）。
使用甘精胰岛素将空腹血糖水平目标控制在 6 年以上，对心血管结局和癌症没有影响。虽然它降低了新发糖尿病的风险，但也增加了低血糖的风险，并适度增加了体重。（由赛诺菲资助；ORIGIN 临床试验.gov 编号，NCT00069784。）
