Abstract Body (Do not enter title and authors here): Background:The efficacy of semaglutide, a glucagon-like peptide-1 receptor agonist, has been studied in patients with type 2 diabetes mellitus (T2DM) who also have advanced chronic kidney disease (CKD) and/or established cardiovascular disease. These conditions pose a high cardiovascular risk. However, the impact of semaglutide on safety outcomes and the incidence of adverse effects in this population remains unclear.
Hypothesis:The use of semaglutide is associated with a higher incidence of gastrointestinal adverse events and specific safety concerns such as severe hypoglycemia and retinopathy.
Aims:This study aimed to evaluate the impact of semaglutide on safety outcomes in high-risk cardiovascular patients with T2DM.
Methods:PubMed, Embase, and Cochrane Central databases were systematically searched in May 2024 for randomized controlled trials (RCTs) that compared semaglutide (oral and subcutaneous) to placebo in adult patients with T2DM with CKD and/or established cardiovascular disease and reported the safety outcomes of (1) gastrointestinal disorder; (2) acute pancreatitis; (2) severe hypoglycemia; (3) retinopathy; (4) acute kidney failure and (5) malignant neoplasm. A systematic review and meta-analysis of the findings were performed using RStudio version 2024.04.0. Heterogeneity was examined with the Cochran Q test and I2 statistics.
Results: We included 3 RCTs in the final analysis, with a total of 10.013 participants, of whom 5.006 (49.99%) were on semaglutide. Semaglutide was associated with a significant increase in the incidence of gastrointestinal disorders compared with placebo (OR 2.00; 95% CI 1.07-3.77; p= 0.031; figure 1A). Severe hypoglycemia (OR 1.10; 95% CI 0.92-1.31; p=0.31; figure 1B), acute kidney failure (OR 0.93; 95% CI 0.78-1.10; p= 0.402), acute pancreatitis (OR 0.92; 95% CI 0.49-1.71; p= 0.792), retinopathy (OR 1.17; 95% CI 0.91, 1.50; p=0.225) and malignant neoplasm (OR 1.02; 95% CI 0.85-1.24; p=0.809) were not significantly different between groups.
Conclusion: In high cardiovascular risk T2DM patients, semaglutide was associated with a higher incidence of gastrointestinal disorders as compared with placebo.