Today at EASD, investigators for the ATTAIN-1 pivotal phase three trial are presenting detailed results for orforglipron in obesity. These results, published yesterday in the New England Journal of Medicine, offer no big surprises. The effectiveness in this 72-week trial was acceptable. But a big question hangs in the air. Will orforglipron be the GLP-1 for a mass market?

Lilly CEO David Ricks clearly thinks so. When he previewed these results last month, he said this product is shaping up according to plans:

“The goal was to create an oral pill that was convenient and can be made at a huge scale, really, for the mass market, and had weight loss that was competitive with other single-acting GLP-1s, and that’s what we’ve achieved.”

Sean Wharton, lead author on the NEJM publication, expresses hope for reaching many more people with this medicine:

“This could mean an expansion of obesity interventions to groups who are currently excluded due to the cost of and lack of access to injectable medications.”

One in Five Lost 20% or More

The ATTAIN-1 trial of this first-in-class, oral, small-molecule GLP-1 receptor agonist enrolled 3,127 adults with obesity but not diabetes. After 72 weeks, patients taking the highest dose (36 mg daily) lost an average of 11.2% of body weight versus 2.1% with placebo. Over half of these patients achieved at least 10% weight loss, and nearly one in five lost 20% or more. Improvements in waist size, blood pressure, triglycerides, and non-HDL cholesterol paralleled the weight loss. Side effects were mainly gastrointestinal, generally mild to moderate, and led to discontinuation in up to 10% of patients.

Proof in the Marketplace

These results suggest orforglipron could broaden access to GLP-1–based obesity treatment by offering an oral option, eliminating the barriers of injection and cold-chain storage. While the degree of weight loss was somewhat less than that reported with injectable semaglutide or tirzepatide, the clinical benefits were clear. Cardiovascular outcomes remain to be studied, and it remains to be seen how Lilly will price and market this product.

Speculation has it that this drug may gain approval by the end of the year under a new, expedited review option at FDA.

Only after that approval will we truly know if orforglipron will mark an important step in expanding safe, effective, and more convenient obesity care. This might be the first scalable obesity medicine to reach a mass market. The proof of this will come in real world use.

Click here for the new study in NEJM, here, here, and here for further reporting on it.

Tablet, Injection Pen, and Vial, illustration by Ted Kyle / ConscienHealth