Association Between Early Weight Loss and Metabolic Outcomes with Tirzepatide in Japanese Patients with Type 2 Diabetes: A SURPASS J Post Hoc Analysis.

INTRODUCTION: This study assessed whether early weight loss following tirzepatide treatment was associated with clinical characteristics and outcomes at 52 weeks in Japanese patients with type 2 diabetes (T2D). METHODS: Post hoc analyses used pooled data from the phase 3 SURPASS J-mono and J-combo studies, which examined tirzepatide 5, 10, and 15 mg as monotherapy or combination therapy in Japanese participants over 52 weeks. Subgroup analyses of clinical characteristics and metabolic outcomes at 52 weeks were conducted based on early weight loss achievement of < 5% or ≥ 5% after 8 weeks of tirzepatide (comprising 4 weeks each at 2.5 mg and 5 mg, per dose-escalation scheme). Selected safety outcomes were evaluated by weight-loss subgroups. RESULTS: The analysis included 893 participants (< 5% subgroup: n = 683 [76.5%]; ≥ 5% subgroup: n = 210 [23.5%]). Multivariate regression analysis showed that participant clinical characteristics, including lower baseline weight, concomitant alpha-glucosidase inhibitor use, and lack of concomitant sulfonylurea use, were independently predictive of achieving ≥ 5% weight loss at 8 weeks. Clinically significant reductions with tirzepatide were observed in body mass parameters over 52 weeks in both subgroups, with greater weight reductions observed at week 52 in the ≥ 5% subgroup versus the < 5% subgroup (5 mg: - 13.8% vs. - 4.1%; 10 mg: - 16.5% vs. - 8.8%; 15 mg: - 20.0% vs. - 11.5% [p < 0.001, all comparisons]). Blood pressure and lipid level improvements were also significantly greater in the ≥ 5% subgroup. Improvements in glycated hemoglobin were similar between subgroups; however, the ≥ 5% subgroup had a higher proportion of participants who achieved normoglycemia at week 52 with a shorter time to reach normoglycemia. Tirzepatide was generally well tolerated across the weight-loss subgroups. CONCLUSIONS: These findings suggest early weight loss following tirzepatide may be predictive of metabolic outcomes at 52 weeks in Japanese patients with T2D. These data may inform clinical management of tirzepatide-treated patients. CLINICALTRIALS: GOV: NCT03861052, NCT03861039.