Orforglipron yields weight loss and A1C reduction in Phase 3

Eli Lilly’s experimental oral GLP-1 receptor agonist, orforglipron, delivered substantial weight loss and improved glucose control in a pivotal Phase 3 trial, marking a potential milestone for obesity treatment if regulatory approvals follow through later this year. In the ATTAIN2 study, adults with overweight or obesity and type 2 diabetes who took the highest daily dose for 72 weeks lost about 22.9 pounds on average and saw meaningful reductions in haemoglobin A1C, alongside improvements in several cardiovascular risk markers. Lilly has signaled plans to submit the therapy for global regulatory approval by the end of 2025 for obesity or weight loss, with diabetes indications to follow in 2026.

In the ATTAIN2 trial, participants were randomly assigned to receive one of three doses of orforglipron (6 mg, 12 mg or 36 mg) or a placebo, continuing for 72 weeks. Across the efficacy estimand, weight loss at 72 weeks reached 5.5% at 6 mg, 7.8% at 12 mg, and 10.5% at 36 mg, compared with 2.2% for placebo. When expressed as weight loss by the treatment-regimen estimand, the figures were 5.1%, 7.0% and 9.6% for the respective doses versus 2.5% with placebo. The highest dose produced the...