Orforglipron produced 12.4% average weight loss in first ATTAIN obesity trial, Lilly says
An oral GLP-1 pill posted a double-digit average weight loss in its first phase 3 obesity trial, though the trial dose was higher than the strength now on the market.
Eli Lilly said on Aug. 7, 2025 that in ATTAIN-1, the first of two pivotal phase 3 obesity trials, adults taking the highest dose of orforglipron who stayed on treatment lost an average of 27.3 pounds, or 12.4% of their body weight, over 72 weeks. People on placebo averaged 2.2 pounds, or 0.9% [1].
The 36 mg dose used in the trial is higher than the highest strength of the approved product, which tops out at 17.2 mg once daily [1]. Whether a 36 mg tablet will ever be sold has not been reported.
The trial enrolled 3,127 adults with obesity or overweight who did not have diabetes and assigned them randomly to orforglipron or placebo under double-blind conditions for 72 weeks [1]. Orforglipron is a small-molecule, non-peptide GLP-1 receptor agonist taken as a once-daily tablet, with or without food [1]. It activates GLP-1 receptors in brain regions that regulate appetite and calorie intake, and it also slows gastric emptying [1].
Lilly reported two sets of weight results. Among participants who remained on treatment, the average loss was 27.3 pounds (12.4%) versus 2.2 pounds (0.9%) for placebo. Across all participants, including those who stopped, the average was 25 pounds (11.1%) versus 5.3 pounds (2.1%) [1].
How many people left the trial early, and for what reasons, has not been reported [1].
The company also said orforglipron was linked to improvements in several cardiometabolic risk markers — waist circumference, non-HDL cholesterol, triglycerides and systolic blood pressure — across all doses tested [1].
Why it matters for patients
Orforglipron, sold as Foundayo, gives adults an option that is swallowed instead of injected [1]. It is approved, alongside a reduced-calorie diet and more physical activity, to lower excess body weight and keep it off long term in adults with obesity, or in adults who are overweight and have at least one weight-related medical condition [1].
Comparing its results head-to-head with other GLP-1 medicines is not straightforward, because the trials studied different groups of people. In ATTAIN-2, which enrolled adults with obesity or overweight who also had type 2 diabetes, the top dose produced an average loss of 22.9 pounds (10.5%) at 72 weeks [1]. In ACHIEVE-3, a head-to-head trial in adults with type 2 diabetes, orforglipron 36 mg cut A1C by 2.2 percentage points versus 1.4 for oral semaglutide (Rybelsus) 14 mg, and weight fell 19.7 pounds (9.2%) versus 11.0 pounds (5.3%) [1].
The Foundayo label carries a boxed warning about thyroid C-cell tumors [1]. Side effects reported in at least 5% of patients include nausea, constipation, diarrhea, vomiting, indigestion, stomach pain, headache, bloating, fatigue, burping, acid reflux, gas and hair loss [1]. The label also warns about pancreatitis, severe gastrointestinal reactions, acute kidney injury from fluid loss, low blood sugar, serious allergic reactions, diabetic retinopathy complications in people with type 2 diabetes, gallbladder disease, and aspiration into the lungs during general anesthesia or deep sedation [1].
What happens next
The FDA approved Foundayo on April 1, 2026 [1]. Complete ATTAIN-1 results were published in the New England Journal of Medicine, with a date of Sept. 16, 2025 [1]. Orforglipron is still being studied for type 2 diabetes, and for obstructive sleep apnea and high blood pressure in adults with obesity [1]. Pricing and insurance coverage have not been disclosed [1].
Sources
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