Comparison of Dose Escalation Versus Switching to Tirzepatide Among People With Type 2 Diabetes Inadequately Controlled on Lower Doses of Dulaglutide : A Randomized Clinical Trial.

BACKGROUND: Tirzepatide, a once-weekly glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist approved for the treatment of adults with type 2 diabetes or obesity, showed clinically meaningful reductions in hemoglobin A(HbA) and body weight in the SURPASS phase 3 clinical trial program. OBJECTIVE: To compare efficacy and safety of escalation of dulaglutide dose versus switching to tirzepatide in inadequately controlled type 2 diabetes. DESIGN: Multicenter, randomized, open-label, phase 4 trial (SURPASS-SWITCH [A Phase 4, Randomized, Open-Label, Active-Controlled Study to Investigate the Efficacy and Safety of Switching from Weekly Dulaglutide to Weekly Tirzepatide in Adults with Type 2 Diabetes], ClinicalTrials.gov: NCT05564039). SETTING: 38 sites across 5 countries. PARTICIPANTS: Adults with HbA7.0% or greater to 9.5% or less, stable body weight, body mass index of 25 kg/mor greater, receiving a stable dose of dulaglutide (0.75 or 1.5 mg) for at least 6 months and 0 to 3 oral antihyperglycemic medications for at least 3 months. INTERVENTION: Escalation of dulaglutide to 4.5 mg or maximum tolerated dose (MTD) or switching to tirzepatide. MEASUREMENTS: The primary end point was change from baseline in HbAat week 40. The key secondary end point was change from baseline in weight at week 40. RESULTS: A total of 282 adults were randomly assigned to tirzepatide ( = 139) or dulaglutide ( = 143). Change from baseline in HbAat week 40 was -1.44% (SE, 0.07) with tirzepatide, 15 mg or MTD, and -0.67% (SE, 0.08) with dulaglutide, 4.5 mg or MTD (estimated treatment difference, -0.77% [95% CI, -0.98% to -0.56%; < 0.001]). Change from baseline in weight at week 40 was -10.5 kg (SE, 0.5) with tirzepatide and -3.6 kg (SE, 0.5) with dulaglutide (estimated treatment difference, -6.9 kg [CI, -8.3 to -5.5 kg; < 0.001]). Serious adverse events were reported by 10 (7.2%) tirzepatide and 10 (7.0%) dulaglutide participants. The most common treatment-emergent adverse events were nausea and diarrhea. LIMITATION: Open-label design. CONCLUSION: In SURPASS-SWITCH, switching treatment to tirzepatide provided additional HbAreduction and weight loss compared with escalating treatment with dulaglutide. PRIMARY FUNDING SOURCE: Eli Lilly and Company.