Oral GLP-1 Drug Shines in Phase III ACHIEVE-1 Trial, Lilly Says

Orforglipron, an oral glucagon-like peptide-1 (GLP-1) receptor agonist, is just as safe as injectable alternatives and more effectively lowers HbA1c levels than placebo in patients with type 2 diabetes and obesity, manufacturer Eli Lilly and Company announced today.

The topline results are from ACHIEVE-1, the first phase III trial of an oral GLP-1 drug to successfully reach completion, a press release notes. Taken as a once-daily pill, orforglipron, unlike oral semaglutide (Rybelsus; Novo Nordisk), requires no restrictions on diet or on the amounts and types of liquid with which it can be taken.

ACHIEVE-1 randomized 559 patients to receive one of three orforglipron doses (3, 12, or 36 mg daily) or placebo for 40 weeks. All three doses significantly reduced HbA1c levels from a baseline of 8.0%, the study’s primary endpoint, in comparison to placebo. Additionally, more than 65% of people on 36 mg of orforglipron achieved an HbA1c less than or equal to 6.5%, below the American Diabetes Association's threshold for diabetes. Orforglipron also led to greater weight loss.

ACHIEVE-1: Topline Results for Efficacy

Notably, “given that participants had not yet reached a weight plateau at the time the study ended, it appears that full weight reduction was not yet attained,” the press release points out.

The most commonly reported adverse events were GI-related and considered generally of mild-to-moderate severity, with no signs of harm to the liver.

ACHIEVE-1: Topline Results for Safety

ACHIEVE-1 is among seven phase III trials being conducted by Eli Lilly across a range of patients with diabetes and obesity. The company plans to release fleshed out results from the study during the upcoming American Diabetes Association annual meeting in June 2025. More data will continue to roll out from ACHIEVE-1, as well as from ATTAIN, another phase III trial of orforglipron but this time focused on weight management.