Phase 2 obesity results: up to 14.7% weight loss at 36 weeks

Eli Lilly reported Phase 2 results for orforglipron, an experimental once-daily GLP-1 pill, in the New England Journal of Medicine on June 23, 2023. In adults with obesity or overweight with at least one weight-related health problem, average body weight dropped 8.6% to 12.6% across orforglipron dose groups at 26 weeks, compared with 2.0% for placebo, and 9.4% to 14.7% at 36 weeks, compared with 2.3% for placebo ^[1].

The trial was registered as NCT05051579, listed on ClinicalTrials.gov as "A Study of LY3502970 in Participants With Obesity or Overweight With Weight-related Comorbidities" ^[2]. LY3502970 was the internal code name for orforglipron.

What makes this drug different

Orforglipron is a small-molecule, non-peptide GLP-1 receptor agonist taken as a tablet ^[1]. That matters because the GLP-1 medicines most Americans know — semaglutide (Ozempic, Wegovy) and tirzepatide (Mounjaro, Zepbound) — are peptides given by injection. Like the injectables, orforglipron works by binding to and activating GLP-1 receptors in brain regions that regulate appetite and calorie intake, and it delays stomach emptying ^[1].

A companion Phase 2 trial in type 2 diabetes (NCT05048719) reported A1C reductions of up to 2.1% with orforglipron at 26 weeks, versus 0.4% with placebo and 1.1% with the injectable dulaglutide. Between 65% and 96% of orforglipron participants reached an A1C below 7.0%, compared with 64% on dulaglutide and 24% on placebo ^[1].

The sources available here do not report the Phase 2 dose levels, the number of participants, side-effect rates or how many people stopped treatment because of side effects. Those details are not yet known from this material.

Why it matters for patients

The practical appeal of a pill is straightforward: no needles, no refrigeration, and a manufacturing process that does not depend on the peptide-filling capacity that caused shortages of injectable GLP-1s. The 36-week Phase 2 numbers — up to 14.7% average weight reduction — landed in the same general range that injectable GLP-1s had reached in their own trials, which is why this readout was widely treated as the moment an oral small-molecule GLP-1 became a serious contender rather than a long shot.

It is worth being careful with Phase 2 numbers. They come from smaller, shorter studies than the trials regulators use to approve a drug, and different trials measure weight loss in different ways. In orforglipron's later Phase 3 obesity trial, ATTAIN-1, the results were reported two ways: participants on the highest dose who stayed on treatment lost an average of 27.3 pounds (12.4%) versus 2.2 pounds (0.9%) on placebo, while counting everyone regardless of whether they finished, the averages were 25 pounds (11.1%) versus 5.3 pounds (2.1%) ^[1]. Both figures come from the same 72-week trial of 3,127 adults ^[1].

What happened next

The Phase 2 results launched two large Phase 3 programs: ACHIEVE for type 2 diabetes and ATTAIN for obesity and overweight ^[1]. In ACHIEVE-3, a head-to-head trial, orforglipron 36 mg lowered A1C by 2.2% versus 1.4% for oral semaglutide 14 mg, and produced 19.7 pounds (9.2%) of weight loss versus 11.0 pounds (5.3%) ^[1].

The FDA approved the drug as Foundayo on April 1, 2026, for adults with obesity or adults with overweight plus at least one weight-related condition, alongside a reduced-calorie diet and more physical activity ^[1]. It is supplied as 0.8 mg, 2.5 mg, 5.5 mg, 9 mg, 14.5 mg and 17.2 mg tablets, taken once daily with or without food, with a maximum of 17.2 mg per day ^[1]. Note that the approved strengths differ from the milligram amounts used in the Phase 3 trials; the sources do not explain why.

Foundayo carries a boxed warning for thyroid C-cell tumors, plus warnings covering acute pancreatitis, severe gastrointestinal reactions, acute kidney injury from dehydration, low blood sugar, serious allergic reactions, diabetic retinopathy complications, gallbladder disease and aspiration during anesthesia ^[1]. The most common side effects reported in at least 5% of patients include nausea, constipation, diarrhea, vomiting, indigestion, abdominal pain, headache, fatigue and hair loss ^[1].