Orforglipron Lowers Systolic BP in ATTAIN-1, ATTAIN-2 Analyses

Orforglipron (Foundayo; Eli Lilly and Company) is the once-daily oral glucagon-like peptide-1 (GLP-1) receptor agonist approved for chronic weight management. Over 72 weeks, it significantly lowered systolic blood pressure (SBP) compared with placebo in adults with obesity, with or without type 2 diabetes (T2D). The findings come from post hoc analyses of the ATTAIN-1 (NCT05869903) and ATTAIN-2 (NCT05872620) trials presented at the American Heart Association (AHA) Scientific Sessions 2026, taking place November 6–9 in Chicago, Illinois.^1-3

For pharmacists managing patients with obesity and hypertension, the largest absolute reductions were in patients with stage 2 hypertension at baseline. The investigators reported that the effect appeared to be at least partly independent of weight loss.¹

The FDA approved orforglipron in April 2026 for adults with obesity or overweight with weight-related medical problems as an adjunct to a reduced-calorie diet and increased physical activity. ATTAIN-1 and ATTAIN-2 supported the approval. The agent is taken once daily without food or water restrictions.⁴

How the Analyses Were Conducted

ATTAIN-1 randomly assigned 3127 adults with obesity and without diabetes to orforglipron 6 mg, 12 mg, or 36 mg or placebo, alongside a healthy diet and physical activity. The primary publication reported that SBP significantly improved with orforglipron, along with waist circumference, triglycerides, and non-high-density lipoprotein cholesterol. ATTAIN-2 randomly assigned 1613 adults with T2D, a body mass index of 27 kg/m² or higher, and glycated hemoglobin of 7% to 10% to the same doses or placebo.^2,3

In the new analyses, investigators evaluated changes in office SBP and diastolic blood pressure (DBP) over time. They also grouped patients by baseline BP category under ACC/AHA criteria:

• 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

REFERENCES

1. Laffin LJ, Plat A, Dennehy E, et al. Effects of orforglipron on blood pressure: post-hoc analyses from ATTAIN-1 and ATTAIN-2 trials. Abstract 7876. Presented at: American Heart Association Scientific Sessions 2026; November 6–9; Chicago, Illinois. Accessed November 6, 2026. https://eppro01.ativ.me/web/page.php?page=Session&project=AHA26&id=S304

2. Wharton S, Aronne LJ, Stefanski A, et al. Orforglipron, an oral small-molecule GLP-1 receptor agonist for obesity treatment. N Engl J Med. 2025;393(18):1796-1806. doi:10.1056/NEJMoa2511774

3. Horn DB, Ryan DH, Kis SG, et al. Orforglipron, an oral small-molecule GLP-1 receptor agonist, for the treatment of obesity in people with type 2 diabetes (ATTAIN-2): a phase 3, double-blind, randomised, multicentre, placebo-controlled trial. Lancet. 2025;406(10522):2927-2944. doi:10.1016/S0140-6736(25)02165-8

4. McGovern G. FDA approves orforglipron, first GLP-1 pill without time, food, or water restrictions. Pharmacy Times. April 1, 2026. Accessed November 6, 2026. https://www.pharmacytimes.com/view/fda-approves-orforglipron-first-glp-1-pill-without-time-food-or-water-restrictions