Efficacy and safety of tirzepatide monotherapy compared with dulaglutide in Japanese patients with type 2 diabetes (SURPASS J-mono): a double-blind, multicentre, randomised, phase 3 trial.
Level 2 - randomized trial
Individual randomized controlled trial
PubMed 35914543 · doi:10.1016/S2213-8587(22)00188-7
What was done
In a multicentre, double-blind, active-controlled, phase 3 trial conducted across 46 centres in Japan, treatment-naïve or oral-monotherapy-discontinued adults aged 20 or older with type 2 diabetes were randomly assigned (1:1:1:1) to receive weekly subcutaneous tirzepatide (5 mg, 10 mg, or 15 mg) or dulaglutide (0.75 mg). Tirzepatide was initiated at 2.5 mg and escalated by 2.5 mg every 4 weeks to target doses. The primary endpoint was the least squares mean change in HbA1c from baseline to week 52 in the modified intention-to-treat population.
What was found
A total of 636 participants were randomised (mean age 56.6 years, SD 10.3; 76% male; 615 [97%] completed the study). At week 52, least squares mean HbA1c decreased from baseline by -2.4% (SE 0.1) for tirzepatide 5 mg, -2.6% (0.1) for 10 mg, -2.8% (0.1) for 15 mg, and -1.3% (0.1) for dulaglutide 0.75 mg. Estimated treatment differences versus dulaglutide were -1.1% (95% CI -1.3 to -0.9) for 5 mg, -1.3% (-1.5 to -1.1) for 10 mg, and -1.5% (-1.71 to -1.4) for 15 mg (all p<0.0001). Least squares mean bodyweight changes were -5.8 kg (-7.8%) for 5 mg, -8.5 kg (-11.0%) for 10 mg, and -10.7 kg (-13.9%) for 15 mg, versus -0.5 kg (-0.7%) for dulaglutide. Common treatment-emergent adverse events included nausea (12% for 5 mg, 20% for 10 mg, 20% for 15 mg, vs 8% for dulaglutide), constipation (15% vs 18% vs 14% vs 11%), and nasopharyngitis (18% vs 16% vs 14% vs 16%).
Why it matters
This trial demonstrates that tirzepatide monotherapy provides clinically meaningful and superior glycemic control and weight reduction compared with dulaglutide in Japanese adults with type 2 diabetes, with a safety profile comparable to GLP-1 receptor agonists.
Limits
The trial was limited to Japanese participants, which may limit generalizability to other ethnic groups with different baseline body composition. The comparator dose of dulaglutide was 0.75 mg weekly, which is standard in Japan but lower than doses used internationally (1.5–4.5 mg). The study population had a high proportion of male participants (76%), and the trial did not assess cardiovascular outcomes or durability past 52 weeks.
Cited by
- supports Standard starting doses of GLP-1 medications are 0.25 mg for semaglutide and 2.5 mg for tirzepatide.