Glycaemic control, body weight, and safety of tirzepatide versus dulaglutide by baseline glycated haemoglobin level in Japanese patients with type 2 diabetes: A subgroup analysis of the SURPASS J-mono study

Aim: To evaluate glycaemic control, body weight, and safety outcomes following treatment with tirzepatide or dulaglutide in patients with type 2 diabetes (T2D) with a baseline haemoglobin (HbA1c) level of <= 8.5% (<= 69 mmol/mol) versus >8.5% (>69 mmol/mol). Materials and methods: SURPASS J-mono was a 52-week, multicentre, randomized, double-blind, parallel, active-controlled, phase 3 study conducted in Japan. In this exploratory subgroup analysis of SURPASS J-mono, we examined mean change in HbA1c and body weight and the incidence of adverse events (AEs) in patients with a baseline HbA1c of <= 8.5% versus >8.5% after treatment with tirzepatide (5, 10 or 15 mg) or dulaglutide 0.75 mg. Results: Of 636 randomized participants, 203 had a baseline HbA1c of >8.5% and 433 had a baseline HbA1c of <= 8.5% (range >= 7.0% to <= 10.0%). Both subgroups showed significantly greater reductions in HbA1c and body weight with any-dose tirzepatide versus dulaglutide 0.75 mg, with greater HbA1c reductions observed in patients with a baseline HbA1c of >8.5% treated with tirzepatide (least squares mean [LSM] differences of -3.13% to -3.86%) or dulaglutide (LSM -1.81%) compared with patients with a baseline HbA1c of <= 8.5% (LSM -2.00% to -2.32%) or dulaglutide (LSM -1.05%; treatment-by-baseline HbA1c subgroup interaction P <= 0.001). For the tirzepatide treatment arms, LSM change from baseline in body weight ranged from -6.7 to -10.7 kg for the baseline HbA1c <= 8.5% subgroup and from -4.0 to -10.6 kg for the baseline HbA1c >8.5% subgroup, compared with -0.6 kg and -0.4 kg, respectively, for the dulaglutide arm. The incidence of hypoglycaemia was low, with no substantial difference in hypoglycaemia or treatment-emergent AEs between subgroups. Conclusions: Regardless of baseline HbA1c (<= 8.5% or >8.5%), tirzepatide at doses of 5, 10 and 15 mg is effective in Japanese patients with T2D compared with dulaglutide 0.75 mg in terms of glycaemic control and body weight reduction, with an adequate safety profile consistent with previous reports.