802-P: A New Dawn beyond Basal Insulin? Dose-Response Meta-analysis for Efficacy and Safety of Tirzepatide Compared with Basal Insulin in Uncontrolled Diabetes Mellitus

Introduction & Objective: Insulin is the mainstay for uncontrolled type 2 diabetes mellitus (T2D) but is associated with hypoglycemia and weight gain. Tirzepatide is a first-in-class dual incretin GLP-1/GIP analog. We assessed the efficacy and safety of Tirzepatide compared to basal insulin for uncontrolled T2D. Methods: We searched PubMed, Scopus, and CENTRAL till 2023/08/02 for relevant RCTs. We compared Tirzepatide 15mg once weekly with basal insulin, and then various doses after confirming dose-response linearity by Wald’s test. Then, we graded the evidence quality. Protocol: CRD42023450278 [PROSPERO] Results: We identified 4,339 patients from 3 RCTs. Tirzepatide 15mg has a greater reduction in HbA1c [-1.23%, -1.53 to -0.93] compared to basal insulin. The 95% prediction interval for expected reduction in clinical practice is -5.04 to 2.58. More patients had >5% weight loss [RR 13.75, 9.91 - 19.09] and adverse events [RR 1.95, 1.66 - 2.30], but not serious adverse events [RR 0.78, 0.53 - 1.16]. There is considerable dose-dependent improvement in efficacy [Figure]. Conclusion: High quality evidence suggests Tirzepatide leads to better glycemic control with an acceptable safety profile, along with benefits like weight loss and decreased frequency of administration. Future studies can inform dose optimization and long-term safety. Disclosure M. Shamim: None. P. Dwivedi: None. P. Aggarwal: None. R. Dwivedi: None. A. Anil: None. A. Saravanan: None. K. Tiwari: None. R.P. Dodiya: None. I. Yadav: None. S. Sukhija: None. S. Varthya: None. R. Shukla: None. S. Singh: None. K. Singh: None.