Aims: Metformin might improve glycemic control in patients with T1D, but whether it has cardiovascular benefit is controversial. We aimed to investigate whether metformin improved cardiac autonomic neuropathy, as measured by heart rate variability (HRV), in patients with T1D.

Methods: This is a secondary analysis of a crossover, randomized trial conducted in adolescents with T1D inadequately controlled with insulin. Patients were randomly received metformin added on insulin for 24 weeks followed by insulin treatment alone for a subsequent 24 weeks or vice versa. The mean amplitude of glycemic excursions (MAGE) was obtained from CGM as a measure of glucose variability, while SD of beat-to-beat (NN) intervals (SDNN), SD of the average NN intervals calculated over 5 minutes (SDANN), the percentage of the interval differences of successive NN intervals greater than 50 ms (PNN50), the square root of the mean squared differences of successive NN intervals (RMSSD), low-frequency (LF) and high frequency (HF) power were assessed by 24-h Holter monitoring as measures of HRV.

Results: Seventeen patients with age 14.4±2.3 years, BMI 18.2±1.8 kg/m2, T1D duration 5.4±3.2 years and HbA1c 9.2±1.6% were enrolled. Changes in HbA1c, BMI, lipid profiles and MAGE were similar between groups. Compared with insulin monotherapy, metformin added on insulin markedly increased SDNN (between group difference [SE], 26.96 [11.77], P=0.034), SDANN (25.62 [12.12], P= 0.049), pNN50 (10.14 [3.05], P= 0.003) and HF (236.08 [83.21], P= 0.01). Changes in RMSSD and LF were not different between groups. In a multivariable regression analysis, the increase in SDNN remained significant after adjusting for ΔHbA1c, ΔMAGE and Δ systolic blood pressure (SBP) (β= 28.62, P= 0.039), suggesting the independent effect of metformin on SDNN.

Conclusions: In adolescent patients with T1D, metformin increased HRV despite no obvious effect on improvement in metabolic parameters.


D. Yang: None. W. Xu: None. H. Deng: None. J. Lv: None. J. Yan: None. B. Yao: None. J. Weng: None.


National Key Research and Development Program of China (2017YFC1309602); Science and Technology Planning Project of Guangdong Province (2017A020215142); Natural Science Foundation of Guangdong Province (2019A1515010979)

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