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
Authors' 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.
Study context
- Population
- Adults with obesity or overweight without (ATTAIN-1) and with Type 2 diabetes (ATTAIN-2), randomized to orforglipron (pooled doses) or placebo
- Comparison
- Orforglipron vs placebo
Methodological detailsexploratory subgroup analyses, exploratory mediation analysis, mixed model of repeated measures
- Exploratory subgroup analyses
- Exploratory mediation analysis
- Mixed model of repeated measures
Primary result
As reported in the abstract
Change in SBP across baseline subgroups · Week 72
- Reductions in systolic blood pressure (SBP) across all baseline subgroups with no clear evidence of heterogeneity in ATTAIN-1 and ATTAIN-2
- Exploratory subgroup analyses
- All interaction p > 0.10
Further findings
Change in diastolic blood pressure (DBP) across baseline subgroups · Week 72
- Reductions in DBP across most of the baseline subgroups in ATTAIN-1
- Greater reduction in DBP among participants with baseline DBP ≥ 80 mmHg compared with baseline DBP < 80 mmHg in ATTAIN-2
- Interaction p = 0.002
Study-visit-office normal blood pressure · Week 72
- Numerically greater proportions of orforglipron-treated participants than placebo in ATTAIN-1 and −2
Proportion of SBP reduction mediated by orforglipron-induced weight reduction
- ATTAIN-1
- 58.3%
- ATTAIN-2
- 80.8%
- Exploratory mediation analysis
- p < 0.001
Safety
Low blood pressure-related adverse events
- Uncommon but more frequent with orforglipron than with placebo; mostly mild to moderate in severity
Original publication
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. Diabetes Obes Metab. Published 10 November 2026. doi:10.
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