Insulin requirements after switching from GLP-1 receptor agonist to dual GIP/GLP-1 receptor agonist in patients with type 2 diabetes mellitus

Introduction: With recent clinical implementation of tirzepatide, patients with type 2 diabetes mellitus (T2DM) are transitioning from glucagon-like peptide 1 receptor agonists (GLP-1 RA) to a dual gastric inhibitory polypeptide (GIP)/GLP-1 RA-like tirzepatide. Limited literature is available for insulin dose adjustments for patients concurrently using insulin during this transition. In clinical trials, tirzepatide has shown greater glycated hemoglobin (A1c) reduction and glucose-lowering effects compared to GLP-1 RAs, such as semaglutide, suggesting a potential elevated risk of hypoglycemia without proactive insulin adjustments. Objectives: The primary objective of this study was to assess the percent change in daily insulin requirements 6 months after transitioning patients from GLP-1 RAs to tirzepatide. Methods: This retrospective cohort study includes patients with T2DM who transitioned from a GLP-1 RA to tirzepatide while concurrently using insulin therapy. Patient-reported doses of insulin and study medications were collected by chart review by investigators, along with baseline demographics and adverse effects as additional endpoints. Results: Sixty-six patients were included. The median insulin dose reduced from 101 units at baseline to 71 units after 6 months, with a median decrease of 9.5 units (p < 0.001). The median percent change in insulin dose was -9.2%. Patients with a baseline A1c of 8.0% or lower required a larger decrease in insulin compared to patients with a higher baseline A1c (-22.6% vs. 0%, p = 0.018). The intensity of GLP-1 RA and tirzepatide, determined by agent and dose, did not show a difference in insulin requirements (p = 0.279 and p = 0.317, respectively). Hypoglycemia occurred in eight patients (12.1%). Conclusion: Patients require a reduction in insulin when transitioning from GLP-1 RAs to tirzepatide, especially if baseline A1c is less than or equal to 8.0%. Larger, comparative studies need to be performed to provide specific recommendations for various doses and product types of incretin receptor agonists.