Switching to Tirzepatide 5 mg from GLP-1 RAs: Clinical Expectations in the First 12 Weeks of Treatment

What were the changes in glycemic outcomes, body weight (BW) and adverse event (AE) occurrence in the first 12-weeks following a switch from GLP-1 RA to tirzepatide 5 mg, omitting 2.5-mg initiation dose?

Methods: This open-label study included participants of≥18yrs with type 2 diabetes (T2D), HbA1c≥6.5% to≤9.0%, and body mass index (BMI)≥25 kg/m^2 who 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 and secondary endpoints were change from baseline (CFB) in HbA1c and CFB in BW and glucose levels assessed by continuous glucose monitoring. Safety was also assessed.

Results: The efficacy analysis set (EAS) included 140 participants 58.3yrs on average, mean baseline HbA1c 7.39%, BMI 35.18 kg/m^2, duration of T2D ~12.4yrs and 55% female. GLP-1 RAs before switching included semaglutide, dulaglutide, and liraglutide (n=77, 59, 3). Mean HbA1c decreased from 7.39% to 6.96% after 12-weeks; mean CFB was -0.43% (p<0.001). Mean BW decreased from 100.42 kg to 98.27 kg, mean CFB was -2.15 kg (p<0.001). Significant changes from baseline in HbA1c and weight were observed in a subgroup analysis of baseline GLP-1 RAs, semaglutide and dulaglutide. At baseline, time above range (TAR,>180 mg/dL) was 22%, time in range (TIR, 71-180 mg/dL) 77%, and time below range (TBR,≤70 mg/dL) 1.1% while at Week-12 they were 15%, 83%, and 3.1% respectively. At Week-12, absolute TAR reduced by -7% (p<0.001); TIR, TBR increased by 6% (p<0.001) and 2% (p<0.05). In the GLP-1 RA subgroups, dulaglutide and semaglutide, TAR reduced (-9% and -7%, respectively; p<0.01) and TIR increased (6% and 5% respectively, p<0.05) while TBR did not change significantly from baseline. Participants (EAS, n=20) had gastrointestinal (GI) events which were mild (n=18) and moderate (n=2) in severity. Three participants discontinued tirzepatide due to AE. There were no deaths or incidences of severe hypoglycemia.

Conclusion: In this prospective study, when people with T2D on stable GLP-1 RA-treatment were switched directly and maintained on tirzepatide 5 mg, they experienced improved glycemic outcomes and additional weight reduction with an acceptable risk of GI AE over 12-weeks.

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Interessenkonflikt

S.J reports consultancy fees from Eli Lilly and Company and Sanofi. Grazia Aleppo has received research support to her institution, Northwestern University, from Dexcom, Emmes, Eli Lilly and Company, Fractyl Health, Insulet, MannKind, Tandem Diabetes, and Welldoc. She has received consulting fees from Dexcom, Insulet, and Medscape. J. S. P., P. S., E. G. V., and B. D. B. are employees and shareholders of Eli Lilly and Company.

Publication History

Article published online:
28 May 2025