- normal (<120 and <80 mm Hg);
- elevated (120-129 and <80 mm Hg);
- stage 1 hypertension (130-139 or 80-89 mm Hg); and
- stage 2 hypertension (≥140 or ≥90 mm Hg).
A mixed model for repeated measures compared overall BP changes between groups.1
Systolic Reductions in Both Trials
At 72 weeks, pooled orforglipron reduced SBP by 6.1 mm Hg vs 0.8 mm Hg with placebo in ATTAIN-1. In ATTAIN-2, SBP fell 4.9 mm Hg vs 1.5 mm Hg (P < .001 for both). DBP also declined significantly more with orforglipron in ATTAIN-1 (−2.5 vs −0.9 mm Hg; P < .001), but not in ATTAIN-2 (−1.3 vs −1.4 mm Hg; P = .87).1
Largest Drops in Stage 2 Hypertension
In both trials, orforglipron produced greater SBP declines than placebo in patients with stage 1 and stage 2 hypertension (P < .001 for all). In ATTAIN-1, SBP fell 7.6 vs 1.7 mm Hg in stage 1 and 15.9 vs 11.1 mm Hg in stage 2. In ATTAIN-2, the reductions were 5.6 vs 2.3 mm Hg and 15.8 vs 8.2 mm Hg, respectively. Placebo groups in the stage 2 subgroups also had sizable declines, so the placebo comparison is central to reading these results.1
DBP changes by category were smaller and closer to placebo. In ATTAIN-1, they were −3.6 vs −2.4 mm Hg in stage 1 and −8.4 vs −6.7 mm Hg in stage 2. In ATTAIN-2, they were −2.4 vs −2.1 mm Hg and −6.5 vs −5.4 mm Hg. The abstract did not report P values for these comparisons.1
Weight Loss Explains Most, but Not All, of the Effect
A mediation analysis found that weight reduction explained about 58% of the SBP change in ATTAIN-1 and 80.8% in ATTAIN-2. The investigators concluded that orforglipron improved SBP across baseline BP categories. They added that the BP-lowering effect appeared at least in part independent of weight loss.1
The findings raise practical questions for pharmacists whose patients already take antihypertensive therapy and are starting orforglipron. These include how closely to track BP as weight comes down and when to flag a regimen for prescriber review. The analysis assessed office readings only and did not report on changes to antihypertensive medications.1
The analyses were post hoc, and the abstract did not report results for participants with normal or elevated baseline BP.1
