Effect of Sodium-Glucose Transporter 2 Inhibitors on Cardiovascular Outcomes in Type 1 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

Background: Cardiovascular disease is a major cause of increasing morbidity and mortality in type 1 diabetes mellitus (T1DM). Although insulin therapy is the cornerstone of T1DM, its difficult use and narrow therapeutic index make it difficult for patients to reach glycated haemoglobin targets, increasing the risk of cardiovascular events. Therefore, the combination of sodium-glucose transporter 2 inhibitors (SGLT2i) can likely improve or provide more cardiovascular benefits to patients with T1DM.

Methods: This study conducted a systematic review and meta-analysis of randomised controlled trials (RCTs) published in PubMed, Scopus, Cochrane Library, Web of Science, and Embase up to 30th June 2024. The data from eligible trials were summarised as mean difference (MD) and standard deviation for continuous methods and 95% confidence interval (CI) and risk ratio (RR) for dichotomous approaches.

Results: There were 16 articles that met the inclusion criteria. Compared with placebo, SGLT2i significantly reduced glycated haemoglobin levels (MD: -0.40%, 95%CI: -0.44% to -0.36%; P<0.00001, I2=37%), and body weight (MD: -3.31kg, 95%CI: -3.67kg to -2.96kg; P<0.00001, I2=70%) in insulin-using patients with T1DM, and did not significantly increase the risk of hypoglycaemia and severe hypoglycaemia. It should be noted that SGLT2i significantly increased the risk of diabetic ketoacidosis acidosis (RR: 4.45, 95%CI: 2.81 to 7.05, P<0.00001, I2=0%).

Conclusion: SGLT2i not only significantly improved glycated haemoglobin and body weight in patients with T1DM but also significantly increased the risk of diabetic ketoacidosis acidosis.