METHODS: In a randomized, placebo-controlled, double-blind, crossover study, 15 individuals with T2D (median HbA1c 50 mmol/mol [6.7%], body mass index 30.1 kg/m2, age 71 years) underwent, in randomized order, 14 days of metformin and placebo treatment, respectively. Each treatment period was preceded by 14 days without any glucose-lowering medicine and concluded by two 4 h mixed meal tests performed in randomized order and separated by >24 h with either continuous intravenous exendin(9-39)NH2 or saline infusion.
RESULTS: Compared to placebo, metformin treatment lowered fasting plasma glucose (mean of differences [MD] 1.4 mmol/L × min [95% CI 0.8-2.0]) as well as postprandial plasma glucose excursions during both saline infusion (MD 186 mmol/L × min [95% CI 64-307]) and exendin(9-39)NH2 infusion (MD 268 mmol/L × min [95% CI 108-427]). The metformin-induced improvement in postprandial glucose tolerance was unaffected by GLP-1R antagonization (MD 82 mmol/L × min [95% CI -6564-170]). Metformin treatment increased fasting plasma GLP-1 (MD 1.7 pmol/L × min [95% CI 0.39-2.9]) but did not affect postprandial GLP-1 responses (MD 820 pmol/L × min [95% CI -1750-111]).
CONCLUSIONS: Using GLP-1R antagonization, we could not detect GLP-1-mediated postprandial glucose-lowering effect of metformin in individuals with T2D. We show that 2 weeks of metformin treatment increases fasting plasma GLP-1, which may contribute to metformin\'s beneficial effect on fasting plasma glucose in T2D. Trial registration: Clinicaltrials.gov NCT03246451.
方法:在随机的,安慰剂对照,双盲,交叉研究,15例T2D患者(HbA1c中位数为50mmol/mol(6.7%),BMI30.1kg/m2,年龄71岁)接受,按随机顺序,二甲双胍和安慰剂治疗14天,分别。每个治疗期之前为14天,没有任何降糖药物,并通过以随机顺序进行的两次4小时混合餐测试结束,并以>24小时的间隔连续静脉注射exendin(9-39)NH2或盐水输注。
结果:与安慰剂相比,二甲双胍治疗可降低空腹血糖(平均差异(MD)1.4mmol/l×min(95%CI0.8-2.0))以及盐水输注(MD186mmol/l×min(95%CI64-307))和exendin(9-39)NH2输注(MD268mmol/l×min(95%CI108-427))。二甲双胍诱导的餐后葡萄糖耐量改善不受GLP-1R拮抗作用的影响(MD82mmol/l×min(95%CI-6,564-170))。二甲双胍治疗可增加空腹血浆GLP-1(MD1.7pmol/l×min(95%CI0.39-2.9)),但不影响餐后GLP-1反应(MD820pmol/l×min(95%CI-1,750-111))。
结论:使用GLP-1R拮抗,我们无法检测到GLP-1介导的二甲双胍在T2D患者中的餐后降糖作用.我们显示,二甲双胍治疗两周可增加空腹血浆GLP-1,这可能有助于二甲双胍对T2D空腹血糖的有益作用。
背景:Clinicaltrials.govNCT03246451。