A Combination of Metformin and Insulin Is an Effective Treatment That Benefits the Cardiovascular and Cerebrovascular System in Individuals With Type 1 Diabetes Mellitus

Background: This study aims to further clarify whether there are cardiovascular and cerebrovascular benefits associated with insulin treatment combined with metformin in individuals with type 1 diabetes. Methods: Electronic databases were searched for randomized controlled trials in which the efficacy and safety of metformin were compared with those of a placebo for the treatment of cardiovascular and cerebrovascular disease among type 1 diabetes patients, and a meta-analysis was conducted. Results: Thirteen cardiovascular studies were identified. In the metformin group, mean carotid intimal media thickness was significantly reduced by 0.03 mm, ascending aortic pulse wave velocity by 6.3 m/s, descending aortic wall shear stress by 1.77 dyn/cm2 (P=0.02), insulin daily dose by 0.05 U/kg/d, body weight by 2.27 kg, fat-free mass by 1.32 kg, body mass index by 0.58 kg/m2, hip circumference by 0.29 m, and low-density lipoprotein by 0.16 mmol/L, all above are P<0.05. In the metformin group, flow-mediated dilation was increased by 1.29%, glucose infusion rate/insulin by 18.22 mg/(kg•min), and waist-to-hip ratio by 0.02, all above are P<0.00001. The metformin group showed no differences in blood pressure, reactive hyperemia index, waist circumference, triglyceride, total cholesterol, high-density lipoprotein cholesterol, or body mass index Z score. For cerebrovascular studies were identified. But none of them had a risk factor assessment. Conclusions: There is strong evidence supporting wider use of metformin to improve cardiovascular and cerebrovascular disease risk among individuals with type 1 diabetes, not just obese or adults. Funding Statement: This work was supported by the National Natural Science Foundation of China (81901106). Declaration of Interests: The authors declare that they have no competing interests. Ethics Approval Statement: This study was approved by the Second Hospital, Cheeloo College of Medicine, Shandong University(KYLL-2017(KJ)P-0016).