The Effect of Metformin on Insulin Requirement, Glycaemic Control and Weight Gain in Type 1 Diabetes During Pregnancy—a Randomised, Placebo-Controlled Multicentre Study
Elina Juuma, Kati Tihtonen, Saara E. Metso, Päivi M. Hannula, Mika Helminen, Kristiina Tertti, Heidi Immonen, Leena Georgiadis, Kirsi Väyrynen, Petteri Ahtiainen, Hilkka Nikkinen, Minna Koivikko, Hannele Laivuori, Jukka Uotila
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引用次数: 0
Abstract
Aim
Our aim was to ascertain whether metformin can reduce insulin requirement without compromising glycaemic control during pregnancy in women with type 1 diabetes.
Methods
A total of 126 pregnant women with type 1 diabetes were recruited for a randomised, double-blind, placebo-controlled multicentre study. The primary outcome was total insulin change, defined as the difference between baseline and third trimester maximum insulin dose (IU).
Results
Fifty women in the placebo group and 51 women in the metformin group completed the study. A predetermined sample size of 200 participants was not achieved. There was no significant difference in the primary outcome, that is, in the change of total insulin requirement (33 vs. 27 IU, p = 0.193). However, the metformin group showed a significantly lower increase in the prandial insulin change, with 24 versus 14 IU (p = 0.014) and 0.3 versus 0.2 IU/kg (p = 0.048). In the exploratory subgroup analysis, metformin attenuated prandial insulin increase in women with high BMI (> 25 kg/m2) or high baseline insulin requirement (> 40 IU) (25 vs. 15 IU, p = 0.028, 30 vs. 14 IU, p = 0.007). Weight gain remained more often within target in the metformin group (20% vs. 40%, p = 0.029). A similar weight benefit was observed in subgroups (BMI> 25 kg/m2 8% vs. 32%, p = 0.005, insulin requirement> 40 IU 6% vs. 34%, p = 0.004). No differences were seen in glycaemic control or neonatal outcome between the groups.
Conclusions
Metformin was not shown to affect total insulin change but reduced the prandial insulin change and improved weight gain control especially in insulin-resistant subgroups. These findings warrant further studies on metformin as an adjunctive medicine.
我们的目的是确定二甲双胍是否可以在不影响1型糖尿病妇女妊娠期间血糖控制的情况下降低胰岛素需求。方法对126例1型糖尿病孕妇进行随机、双盲、安慰剂对照的多中心研究。主要结果是总胰岛素变化,定义为基线和妊娠晚期最大胰岛素剂量(IU)之间的差异。结果安慰剂组50名妇女和二甲双胍组51名妇女完成了研究。没有达到预定的200名参与者的样本量。两组的主要结局,即总胰岛素需要量的变化没有显著差异(33对27 IU, p = 0.193)。然而,二甲双胍组在膳食胰岛素变化方面的增幅明显较低,分别为24 IU/kg和14 IU/kg (p = 0.014), 0.3 IU/kg和0.2 IU/kg (p = 0.048)。在探索性亚组分析中,二甲双胍降低了高BMI (25 kg/m2)或高基线胰岛素需求(40 IU)女性的膳食胰岛素升高(25 vs 15 IU, p = 0.028, 30 vs 14 IU, p = 0.007)。二甲双胍组的体重增加更常保持在目标范围内(20% vs 40%, p = 0.029)。在亚组中也观察到类似的体重益处(体重指数25 kg/m2 8% vs 32%, p = 0.005,胰岛素需求40 IU 6% vs 34%, p = 0.004)。两组间血糖控制和新生儿结局均无差异。结论二甲双胍不影响总胰岛素变化,但可降低膳食胰岛素变化,改善体重增加控制,尤其是在胰岛素抵抗亚组中。这些发现为二甲双胍作为辅助药物的进一步研究提供了依据。临床试验注册:NCT03765359。
期刊介绍:
Diabetes/Metabolism Research and Reviews is a premier endocrinology and metabolism journal esteemed by clinicians and researchers alike. Encompassing a wide spectrum of topics including diabetes, endocrinology, metabolism, and obesity, the journal eagerly accepts submissions ranging from clinical studies to basic and translational research, as well as reviews exploring historical progress, controversial issues, and prominent opinions in the field. Join us in advancing knowledge and understanding in the realm of diabetes and metabolism.