University of Canberra, Locked Bag 1, Canberra, ACT, 2601, Australia.
The Australian National University, Canberra, ACT, 2600, Australia.
Acta Diabetol. 2020 Nov;57(11):1359-1366. doi: 10.1007/s00592-020-01559-9. Epub 2020 Jun 30.
The aim of this study was to investigate the effectiveness of metformin in diabetes prevention in a prediabetic population across a range of fasting plasma glucose (FPG) levels at baseline. A secondary aim was to assess the effectiveness of metformin in preventing diabetes in those participants where impaired fasting glucose (IFG) was relatively more pronounced as opposed to impaired glucose tolerance (IGT).
Participants randomised to metformin and placebo arms in the Diabetes Prevention Program study were stratified into cohorts according to level of FPG at baseline. Cumulative incidence of diabetes for the different cohorts was assessed. Change in FPG, insulin sensitivity, and levels of fasting insulin and proinsulin for the different cohorts were also calculated.
The largest reductions in incidence of diabetes and FPG occurred within prediabetic persons with a higher level of FPG at baseline. Metformin was able to stabilise insulin sensitivity in every stratified sub-cohort except one. Sub-cohorts which had higher levels of insulin sensitivity at baseline experienced the largest increases in insulin sensitivity. Metformin reduced the incidence of diabetes by 43% (RR 0.57, CI 0.4-0.9) in those prediabetic persons whose IFG was more pronounced compared to a 26% (RR 0.74 CI 0.7-0.8) when all participants in the study were included.
The largest reductions in both incidence of diabetes and FPG occurred in prediabetic persons with a higher level of FPG at baseline. Metformin was able to stabilise insulin sensitivity and was more effective in persons with more pronounced IFG.
本研究旨在探讨二甲双胍在不同空腹血糖(FPG)水平的糖尿病前期人群中的预防糖尿病的效果。次要目的是评估二甲双胍在预防那些空腹血糖受损(IFG)较明显而非葡萄糖耐量受损(IGT)的参与者中发生糖尿病的有效性。
将糖尿病预防计划研究中随机分配到二甲双胍和安慰剂组的参与者根据基线时的 FPG 水平分层为不同队列。评估不同队列的糖尿病累积发生率。还计算了不同队列的 FPG、胰岛素敏感性以及空腹胰岛素和胰岛素原水平的变化。
在基线 FPG 水平较高的糖尿病前期人群中,糖尿病和 FPG 的发生率下降幅度最大。除了一个亚组外,二甲双胍能够稳定每个分层亚组的胰岛素敏感性。基线胰岛素敏感性水平较高的亚组经历了最大的胰岛素敏感性增加。与包括研究中的所有参与者时相比,在 IFG 更为明显的糖尿病前期人群中,二甲双胍使糖尿病的发生率降低了 43%(RR 0.57,CI 0.4-0.9),而在研究中所有参与者中,这一比例降低了 26%(RR 0.74 CI 0.7-0.8)。
在基线 FPG 水平较高的糖尿病前期人群中,糖尿病和 FPG 的发生率下降幅度最大。二甲双胍能够稳定胰岛素敏感性,在 IFG 更为明显的人群中更为有效。