Effect of Sodium-glucose Transporter 2 Inhibitors on Cardiovascular Outcomes in Type 1 Diabetes Mellitus: A Systematic Review and Meta-analysis of Randomized 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 hemoglobin 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 randomized controlled trials published in PubMed, Scopus, Cochrane Library, Web of Science, and Embase up to June 30, 2024. The data from eligible trials were summarized as mean difference (MD) and SD for continuous methods and 95% 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 hemoglobin levels (MD: -0.40%, 95% CI, -0.44 to -0.36; P < .00001, I2 = 37%), and body weight (MD: -3.31 kg, 95% CI, -3.67 to -2.96; P < .00001, I2 = 70%) in insulin-using patients with T1DM, and did not significantly increase the risk of hypoglycemia and severe hypoglycemia. It should be noted that SGLT2i significantly increased the risk of diabetic ketoacidosis acidosis (RR: 4.45, 95% CI, 2.81-7.05, P < .00001, I2 = 0%).

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