This prospective study aimed to describe the clinical course in terms of glycemic outcomes, body weight, and adverse events during the first 12 weeks following a switch from GLP-1 RAs directly to tirzepatide 5 mg.

Participants were ≥18 years with type 2 diabetes (T2D), HbA1c ≥6.5% to ≤9.0%, body mass index (BMI) ≥25 kg/m2 and were on a stable treatment dose of GLP-1 RAs (liraglutide once-daily (QD) [1.2, 1.8 mg], semaglutide once-weekly (QW) [0.5, 1.0, 2.0 mg], or dulaglutide QW [0.75, 1.5, 3.0, 4.5 mg]) for ≥3 months at baseline. The primary endpoint was HbA1c change from baseline at Week 12. Secondary endpoints included change from baseline in fasting serum glucose (FSG), body weight, and glucose assessed by continuous glucose monitoring. Safety was also assessed.

Participants were 58.3 years on average, with baseline HbA1c 7.39%, BMI 35.18 kg/m2, T2D duration around 12.4 years, and included 55% females. Dulaglutide (42%) and semaglutide (55%) were the most commonly used GLP-1 RAs at baseline with dulaglutide 1.5 mg and semaglutide 1.0 mg being the most common treatment doses. At Week 12, mean HbA1c changed from baseline by -0.43%, FSG by -7.83 mg/dL, and body weight by -2.15 kg (all p<0.001). Glycemic outcomes and body weight improved in participants in all baseline GLP-1 RA subgroups. Twenty participants (13.2%) developed gastrointestinal events. Three (2%) participants discontinued tirzepatide due to adverse events. There were no severe hypoglycemic events or deaths.

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 over 12 weeks.