MON-515 Efficacy and Safety of Once-Weekly Insulin Efsitora Compared to Daily Insulin Degludec in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis

Abstract Disclosure: A. Ahmed: None. M. Ali: None. N.U. saleem: None. P. Saif: None. S. abid: None. H. Irfan: None. H.A. Mehdi: None. H. Ahmad: None. M. Hamza: None. M. Saeed: None. Z. Iftikhar: None. F. Ahmed: None. S. Joshi: None. H. Raza: None. F. Azhar: None. S. Eltawansy: None. Background: Insulin efsitora is a novel ultra-long-acting basal insulin analogue designed for once-weekly administration. Reducing injection frequency can potentially improve patients’ adherence and disease control. This study aims to evaluate the efficacy and safety of once-weekly insulin efsitora compared to daily insulin degludec in managing type 2 diabetes, providing insights into its potential as a more convenient therapeutic option for patients. Methods: This study was conducted in accordance with the PRISMA guidelines. A comprehensive search of three databases and ClinicalTrials.gov was performed through November 2024 to identify eligible studies. Only randomized controlled trials (RCTs) that compared the efficacy and safety of insulin efsitora with insulin degludec in type 2 diabetes were included. The extracted data were then analyzed for meta-analysis using RevMan 5.3 software. Results: Three RCTs involving 1,605 patients met the inclusion criteria for this analysis. The pooled results revealed no statistically significant differences between once-weekly insulin efsitora and daily insulin degludec in terms of changes in HbA1c (MD: -0.01, 95% CI: -0.11), fasting plasma glucose levels (MD: -0.16, 95% CI: -5.03 to 4.71), body weight (MD: 0.15, 95% CI: -0.15 to 0.46), and time within the glucose target range (MD: 0.43, 95% CI: -1.56 to 2.43). Additionally, no significant differences were observed in the risk of serious adverse events (RR: 1.03, 95% CI: 0.72 to 1.47), hypersensitivity reactions (RR: 1.79, 95% CI: 0.84 to 3.82), injection-site reactions (RR: 1.39, 95% CI: 0.69 to 2.80), and treatment-emergent adverse events (RR: 1.11, 95% CI: 0.96 to 1.28). The pooled estimates for hypoglycemia also showed no significant differences, including level 1 hypoglycemia (RR: 1.13, 95% CI: 0.95 to 1.35), level 2 or 3 hypoglycemia (RR: 1.09, 95% CI: 0.76 to 1.51), level 1 nocturnal hypoglycemia (RR: 0.80, 95% CI: 0.55 to 1.15), and level 2 or 3 nocturnal hypoglycemia (RR: 0.81, 95% CI: 0.62 to 1.05). Furthermore, the risk of major cardiovascular events (RR: 0.92, 95% CI: 0.18 to 4.71) and mortality (RR: 0.67, 95% CI: 0.20 to 2.26) were comparable between the two treatment groups. Conclusion: In conclusion, our research suggests that once-weekly insulin efsitora and daily insulin degludec exhibit comparable efficacy and safety profiles in the management of type 2 diabetes mellitus. Both treatments showed similar effects on key glycemic control markers, including HbA1c, fasting plasma glucose levels, and time in range. These results emphasize the need for more extensive, well-powered trials to investigate further the long-term efficacy, safety, and patient-reported outcomes of once-weekly insulin efsitora. Presentation: Monday, July 14, 2025