(16.07) Switching to tirzepatide 5 mg from GLP-1 RAs: Clinical expectations in the first 12 weeks of treatment

This study aimed to describe the clinical course in terms of changes in glycemic outcomes and body weight and adverse event occurrence in the 12 weeks following a switch from GLP-1 RA to tirzepatide 5 mg, with the 2.5-mg initiation dose omitted.

Methods:

In this open-label study, participants were ≥18 years old with type 2 diabetes (T2D), HbA1c ≥6.5% to ≤9.0%, and body mass index (BMI) ≥25 kg/m², and were on a stable treatment dose of GLP-1 RAs for ≥3 months (liraglutide 1.2 or 1.8 mg once daily, dulaglutide 0.75, 1.5, 3, or 4.5 mg once weekly [QW], or injectable semaglutide 0.5, 1, or 2 mg QW). Tirzepatide 5 mg QW was initiated for 12 weeks. The primary endpoint was change from baseline in HbA1c at Week 12. Secondary endpoints included change from baseline in fasting serum glucose (FSG), body weight, and glucose levels assessed by continuous glucose monitoring. Safety was also assessed.

Results:

Of 152 participants who received treatment, 140 were included in the efficacy analysis set. GLP-1 RAs before switching included semaglutide (n=77), dulaglutide (n=59), and liraglutide (n=3). The overall study population was 58.3 years old on average, with mean baseline HbA1c 7.39%, BMI 35.18 kg/m², and duration of T2D approximately 12.4 years, and was 55% female. Mean HbA1c decreased from 7.39% to 6.96% after 12 weeks; mean change from baseline was -0.43% (p < 0.001). Mean FSG levels decreased from 140.24 mg/dL to 132.85 mg/dL after 12 weeks; mean change from baseline was -7.83 mg/dL (p < 0.001). Similarly, mean body weight decreased from 100.42 kg to 98.27 kg after 12 weeks; mean change from baseline was -2.15 kg (p < 0.001). Significant changes from baseline in HbA1c, FSG, and weight were observed in a subgroup analysis of baseline GLP-1 RAs, semaglutide and dulaglutide. Continuous glucose monitored time above range (TAR, >180 mg/dL) reduced by 7.4% at Week 12 (p < 0.001). Baseline TAR was 22.0%, while at Week 12 it was 14.6%. In the baseline GLP-1 RA subgroups, dulaglutide and semaglutide showed consistent TAR reductions at Week 12 (-9.0% and -6.7%, respectively; p< 0.01). Participants (n=20, 13.2%) had gastrointestinal (GI) events, including nausea, constipation, and diarrhea, which were mild (n=18) and moderate (n=2) in severity. Three participants discontinued tirzepatide due to adverse events. There were no deaths or incidences of severe hypoglycemia.

Discussion/Conclusion:

In this prospective study, when people with T2D on stable GLP-1 RA treatment were switched directly to tirzepatide 5 mg, they experienced improved glycemic outcomes and additional weight reduction with an acceptable risk of adverse GI events during the first 12 weeks.