PubMed30 Mar 2026BMJ open diabetes research & care● 6/10i Safety and efficacy of switching from dulaglutide to tirzepatide across clinically relevant baseline characteristics in participants with T2D: subgroup analysis of SURPASS-SWITCH.
Violante-Ortiz R, Rose L, Sharma P, Gomez Valderas E, Chivukula KK et al.
Switching from dulaglutide to tirzepatide provided superior HbA1c reduction (greater in high baseline HbA1c, low BMI) and weight loss (greater in non-Hispanic populations) across all patient subgroups at 40 weeks. Phase IV RCT, open-label, active-controlled, adults with type 2 diabetes on stable dulaglutide for 6+ months. This is the first head-to-head switching study between GLP-1 agents, establishing tirzepatide's superiority over Novo's dulaglutide across diverse patient populations.
Strategic Signal
This subgroup analysis strengthens Eli Lilly's commercial positioning against Novo Nordisk's dulaglutide by demonstrating consistent superiority across patient types that matter to prescribers making switching decisions. US endocrinologists now have evidence supporting tirzepatide switches regardless of patient characteristics, which removes clinical hesitation around switching criteria. The broad efficacy profile supports unrestricted formulary positioning and counters any payer attempts to limit tirzepatide to specific patient subsets, following the pattern established when SGLT2 inhibitors displaced older diabetes drugs through consistent subgroup benefits.
Original Abstract
INTRODUCTION: In SURPASS-SWITCH, switching from dulaglutide to tirzepatide resulted in greater improvements in glycemic control and body weight in adults with type 2 diabetes (T2D). This study aimed to investigate the efficacy and safety of switching from weekly dulaglutide to weekly tirzepatide in adults with T2D in prespecified baseline subgroups from SURPASS-SWITCH. RESEARCH DESIGN AND METHODS: This phase IV, randomized, open-label, active-controlled, parallel-group, multicenter, multinational trial included adults with hemoglobin A1c (HbA1c) ≥7.0% to ≤9.5%, on a stable dose of dulaglutide for at least 6 months, on a stable dose of 0-3 oral antihyperglycemic medications for at least 3 months, with stable body weight, and body mass index (BMI) ≥25 kg/m2 at screening. Participants were randomly assigned 1:1 to continue with and escalate to dulaglutide 4.5 mg or maximum tolerated dose (MTD) or switch to tirzepatide with escalation to 15 mg or MTD. Changes from baseline in HbA1c and body weight at week 40 in baseline subgroups of age (<65, ≥65 years), HbA1c (≤8.5%, >8.5%), duration of T2D (≤5, >5 to ≤10, >10 years), baseline dulaglutide dose (0.75 mg, 1.5 mg), duration of dulaglutide dose (<1, ≥1 year), BMI (<27, ≥27; <30, ≥30 to <35, ≥35 kg/m2), and ethnicity (Hispanic or Latino, non-Hispanic or non-Latino), and sex (female, male) were determined. RESULTS: Reductions in HbA1c and body weight at week 40 were significant and consistently greater with tirzepatide across all prespecified baseline subgroups. HbA1c reduction was greater in the subgroups with higher baseline HbA1c and low baseline BMI. Weight reduction was greater for participants in the non-Hispanic or non-Latino subgroup. The safety profile was similar across subgroups. Nausea and diarrhea were usually the most frequently reported treatment-emergent adverse events in each subgroup. CONCLUSIONS: In this subgroup analysis of SURPASS-SWITCH, switching to tirzepatide from dulaglutide was generally well-tolerated and associated with significant and consistent improvements in HbA1c and weight reductions versus dulaglutide across all baseline subgroups evaluated. These results indicate that switching to tirzepatide may provide a clinical option across a range of baseline characteristics when treatment goals are not being met with dulaglutide. TRIAL REGISTRATION NUMBER: NCT05564039.