Tirzepatide is a novel glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist (RA) that is approved for the treatment of type 2 diabetes mellitus (T2D). Despite its similarities to GLP-1 RA, there is a lack of data on how to switch between GLP-1 RA and GIP/GLP-1 RA.The objective of this study is to evaluate the efficacy and safety of switching from GLP-1 RA to tirzepatide in patients with T2D and provide guidance for switching between the two classes.This was a retrospective case series of patients with T2D who met protocol criteria for switching between the two classes. Hemoglobin A1C (A1C) and weight data were evaluated at 3 and 6 months.A total of 10 patients were included. Mean change from baseline in A1C was -0.7 ± 0.9% at 3 months (N = 8) compared to -1.4 ± 0.7% at 6 months (N = 4). Percentage of patients who achieved their goal A1C was 25% (2/8) at 3 months post switch compared to 50% (2/4) at 6 months. Mean change from baseline in weight was -3.6 ± 2.3 kg at 3 months and -6 ± 3.4 kg at 6 months. Percentage of patients who achieved weight loss from baseline of ≥10% was 0 at 3 months versus 33.3% (1/3) at 6 months. Few adverse events were reported after switching.Switching can be considered for patients with T2D that require further A1C and weight reduction to reach their target goals despite being on GLP-1 RA.