The Effects of Non-Insulin Anti-Diabetic Medications on the Diabetic Microvascular Complications: A Systemic Review and Meta-Analysis of Randomized Clinical Trials

Objectives: This systemic review focused on the clinical implications of diabetic microvascular complications by non-insulin anti-diabetic medications. Search Methods: We searched the Medical Subject Headings (MESH) combined with entry terms and screened the published literature for previously conducted randomized clinical trials (RCTs) reporting the effects of drugs on diabetic microvascular complications Data Collection and Analysis: We extracted the indices of the continuous variables of estimated glomerular filtration rate (eGFR) and urinary albumin to creatinine ratio (UACR) or urinary albumin excretion rate (UAE) for all studies reporting the results on renal microvascular complication; continuous variables indices of measures for cardiovascular autonomic neuropathy (CAN), vibration detection threshold (VDT), or dichotomous variables indices of risk for DPN; continuous variables of retinal nerve fiber thickness (RNFL) or dichotomous variables indices of risk for DR. When sufficient clinical data and statistical homogeneity existed, we conducted a meta-analysis using random effects models. Certain non-insulin anti-diabetic medications and the indicated anti-diabetic medications used in the RCTs were compared.Main Results: According to the analyses, metformin (MET) may decrease the eGFR by 19 mL/min*1.73m2 (p < 0.05) compared to medications such as sulfonylurea (SUs). The UACR or UAE results showed variations in the effects and significance of the decline. In addition, we compiled various standard measures of the DPN or DR and discovered that the effect and significance of each medication varied. Funding: This work was supported by the Project of Key Medical Discipline of Pudong Hospital of Fudan University (Zdxk2020-11), Project of Key Medical Specialty and Treatment Center of Pudong Hospital of Fudan University (Zdzk2020-24), Integrative Medicine special fund of Shanghai Municipal Health Planning Committee (ZHYY- ZXYJHZX-2-201712), Special Department Fund of the Pudong New Area Health Planning Commission (PWZzk2017-03), Outstanding Leaders Training Program of Pudong Health Bureau of Shanghai (PWR12014-06), Pudong New Area Clinical Plateau Discipline Project (PWYgy-2021-03), the Natural Science Foundation of China (21675034), National Natural Science Foundation of China (81370932), Shanghai Natural Science Foundation (19ZR1447500), Fudan Zhangjiang Clinical Medicine Innovation Fund Project (KP0202118), Talents Training Program of Shanghai Pudong Hospital (YQ202101). Declaration of Interest: We declared no conflict of potential interest.