7018 Improved Tolerability After Transitioning from Glucagon-like Peptide-1 Receptor Agonists to Tirzepatide
Authors: Hudson Sydney , Aurora John , Erenler Feyza 
Published: October 2024

Abstract
Disclosure: S. Hudson: None. J. Aurora: None. F. Erenler: None.
Background: Tirzepatide is a dual incretin targeting glucagon-like peptide-1 receptor agonist (GLP-1RA) and glucose-dependent insulinotropic polypeptide receptor agonist (GIP-RA) with potent reductions in HbA1c and weight, especially compared to semaglutide, a GLP-1RA (1). Gastrointestinal (GI)-related events are commonly associated with incretins. As an imbalanced dual agonist, tirzepatide has a stronger affinity for GIP compared to GLP-1 receptors (2). This stronger affinity for GIP receptors may be related to the improved tolerability of tirzepatide, as GIP is not as associated with GI effects as compared to GLP-1 (2). There is a reported dose-dependent increase in GI events and treatment discontinuation with tirzepatide compared to semaglutide in RCTs, although this has not been corroborated in real-world data (1). Additionally, there is no literature evaluating GI tolerability when switching from GLP-1 receptor agonists to tirzepatide. We present a case series to highlight improved tolerability and sustained clinical outcomes observed in patients transitioning from GLP-1RA to tirzepatide, who previously had GI intolerances. Clinical Case A retrospective review was conducted of five patients who started on GLP-1RA for either T2DM (n=3) or obesity (n=2) but stopped due to GI-related events. All patients were female with a mean age of 57 years. On average, patients with T2DM had a 23-year duration of diabetes, HbA1c 8.4%, weight 78.4 kg, and BMI 29.5 kg/m2 prior to starting tirzepatide. For patients without T2DM, the average weight was 75.9 kg and BMI 30.0 kg/m2 prior to starting tirzepatide. Before switching to tirzepatide, three patients were on maximally tolerated dulaglutide and two patients were on semaglutide. Patients were initially transitioned to tirzepatide 2.5 mg (n=2), 5 mg (n=2), and 7.5 mg (n=1). All patients tolerated tirzepatide with no GI-related events after an average of 6 months of treatment. Of the three patients with T2DM, they saw an additional average HbA1c reduction of 1.1% and an average weight loss of 3%. For patients who transitioned to tirzepatide for weight loss, they saw an additional average weight loss of 9%. Clinical Implications Tirzepatide may offer improved tolerability in patients who are intolerant of GLP-1RA drugs, while yielding further glycemic lowering and weight loss. Given tirzepatide’s stronger affinity to GIP than GLP-1 receptors, this may explain improved GI tolerability as seen in our case series. Further research is needed to evaluate tolerability improvement with tirzepatide using real-world data and larger sample sizes. References 1. Frías JP, Davies MJ, Rosenstock J, et al. Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes. N Engl J Med. 2021;385(6):503-515 2. Willard FS, Douros JD, Gabe MB, et al. Tirzepatide is an imbalanced and biased dual GIP and GLP-1 receptor agonist. JCI Insight. 2020;5(17):e140532
Presentation: 6/3/2024