Association Between Orforglipron and Blood Pressure in Adults With Obesity With or Without Type 2 Diabetes: Post Hoc Analyses From ATTAIN‐1 and ATTAIN‐2 Trials

INTRODUCTION: This post hoc analysis assessed the association between orforglipron and blood pressure in adults with obesity or overweight without (ATTAIN-1) and with Type 2 diabetes (T2D; ATTAIN-2). METHODS: This study included ATTAIN-1 and ATTAIN-2 participants randomized to receive orforglipron (pooled doses) or placebo. A mixed model of repeated measures was used to assess changes in blood pressure across baseline subgroups at Week 72. The association between weight change and systolic blood pressure (SBP) was evaluated by exploratory mediation analysis. Blood-pressure-related adverse events were also reported. RESULTS: Exploratory subgroup analyses reflected reductions in SBP across all baseline subgroups with no clear evidence of heterogeneity in ATTAIN-1 and ATTAIN-2 (all interaction p > 0.10). Reductions in diastolic blood pressure (DBP) were observed across most of the baseline subgroups in ATTAIN-1, while a greater reduction in DBP was observed among participants with baseline DBP ≥ 80 mmHg compared with those who had baseline DBP < 80 mmHg in ATTAIN-2 (interaction p = 0.002). At Week 72, numerically greater proportions of orforglipron-treated participants achieved study-visit-office normal blood pressure than placebo in ATTAIN-1 and -2. Mediation analysis suggests that 58.3% and 80.8% of the reduction in SBP was estimated to be mediated by orforglipron-induced weight reduction in ATTAIN-1 and -2, respectively (p < 0.001). Low blood pressure-related adverse events were uncommon but more frequent with orforglipron treatment than with placebo, and were mostly mild to moderate in severity. CONCLUSION: In these post hoc analyses of ATTAIN-1 and -2, reductions in SBP were broadly consistent across baseline subgroups, with no clear evidence of heterogeneity. The changes were estimated to be largely mediated by weight loss, and potential weight-independent effects on blood pressure require further evaluation.