Orforglipron

Orforglipron (development code LY3502970) is an experimental medicine from Eli Lilly — the same manufacturer as Mounjaro and the also not-yet-approved retatrutide. What makes orforglipron unique is that it is the first non-peptide GLP-1 receptor agonist.

Existing GLP-1 medications such as Ozempic, Wegovy and Saxenda are peptide medicines (small proteins) that are broken down in the stomach — hence the injection form. Rybelsus gets around this with an absorption enhancer, but requires a strict fasting protocol. Orforglipron is a small synthetic molecule that activates the GLP-1 receptor without being broken down — so you can simply take it as a tablet, with no timing restrictions and no injection.

Orforglipron is expected to make its mark on the GLP-1 medication landscape: it will be particularly attractive for patients who want to avoid injections without the strict fasting rules of Rybelsus, and who value the higher effectiveness (~15%).

The phase 2 GZGI study (Wharton et al., published in The New England Journal of Medicine, June 2023) showed weight loss of 9.4% to 14.7% after 36 weeks in 272 obese adults without diabetes, depending on the dose (12 mg to 45 mg daily). Placebo produced 2.3% weight loss over the same period.

Side effects were gastrointestinal and comparable to existing GLP-1s: nausea (32%), diarrhoea (20%), constipation (14%) and vomiting (10%). The discontinuation rate due to side effects was 10-17% at the highest dose.

Phase 3 ATTAIN-1 (obesity without diabetes) and ATTAIN-2 (obesity with diabetes) started in 2024-2025. Results are expected in late 2026. The ACHIEVE programme for type 2 diabetes is also ongoing.