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30 Oct 2026 · Orforglipron

Orforglipron, a once-daily GLP-1 tablet, in obesity with type 2 diabetes (ATTAIN-2)

Studied in
1,613 adults with a BMI of 27 or more and type 2 diabetes
Design
Randomised, double-blind, placebo-controlled, 72 weeks
Evidence
A · Human RCT

What was studied

Orforglipron is not a peptide: it is a small molecule, taken as a daily tablet, that activates the GLP-1 receptor, the same target as semaglutide. Adults at 136 sites in ten countries received 6 mg, 12 mg or 36 mg, or placebo, alongside lifestyle advice.

What was found

Average weight change at 72 weeks was −5.1%, −7.0% and −9.6% on the three doses, against −2.5% on placebo, and HbA1c and the other cardiometabolic measures improved. Side effects were mostly mild-to-moderate stomach upset during dose escalation; 6.1–9.9% stopped because of adverse events, against 4.1% on placebo.

What it doesn’t tell us

The trial was funded by the manufacturer. It made no head-to-head comparison with injected GLP-1 drugs, so it can’t say how a tablet compares with an injection. It also doesn’t show what happens to weight after stopping.

Source · Horn DB et al. 2025, LancetPubMedDOI