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 HbA 7.0% or greater to 9.5% or less, stable body weight, body mass index of 25 kg/m or 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 HbA at 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 HbA at 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 HbA reduction and weight loss compared with escalating treatment with dulaglutide.

PRIMARY FUNDING SOURCE

Eli Lilly and Company.